Search results for: brain volume

Authors: Alexandra K. Diem, Giles Richardson, Roxana O. Carare, Neil W. Bressloff

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Alzheimer's disease (AD) is the most common form of dementia and although it has been researched for over 100 years, there is still no cure or preventive medication. Its onset and progression is closely related to the accumulation of the neuronal metabolite Aβ. This raises the question of how metabolites and waste products are eliminated from the brain as the brain does not have a traditional lymphatic system. In recent years the rapid uptake of Aβ into cerebral artery walls and its clearance along those arteries towards the lymph nodes in the neck has been suggested and confirmed in mice studies, which has led to the hypothesis that interstitial fluid (ISF), in the basement membranes in the walls of cerebral arteries, provides the pathways for the lymphatic drainage of Aβ. This mechanism, however, requires a net reverse flow of ISF inside the blood vessel wall compared to the blood flow and the driving forces for such a mechanism remain unknown. While possible driving mechanisms have been studied using mathematical models in the past, a mechanism for net reverse flow has not been discovered yet. Here, we aim to address the question of the driving force of this reverse lymphatic drainage of Aβ (also called perivascular drainage) by using multi-scale numerical and analytical modelling. The numerical simulation software COMSOL Multiphysics 4.4 is used to develop a fluid-structure interaction model of a cerebral artery, which models blood flow and displacements in the artery wall due to blood pressure changes. An analytical model of a layer of basement membrane inside the wall governs the flow of ISF and, therefore, solute drainage based on the pressure changes and wall displacements obtained from the cerebral artery model. The findings suggest that an active role in facilitating a reverse flow is played by the components of the basement membrane and that stiffening of the artery wall during age is a major risk factor for the impairment of brain lymphatics. Additionally, our model supports the hypothesis of a close association between cerebrovascular diseases and the failure of perivascular drainage.

Keywords: Alzheimer's disease, artery wall mechanics, cerebral blood flow, cerebral lymphatics

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Authors: Naim Izet Kajtazi

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Context: The third ventricle colloid cyst (CC) is a benign growth usually located in the third ventricle and can cause various neurological symptoms, including sudden death. Modern surgical interventions may still result in a wide range of complications and cerebral venous thrombosis (CVT) is among them. Process: A 38-year-old female with an existing diagnosis of diabetes mellitus (DM) and hypothyroidism and a six-month history of headaches, blurred vision, and vomiting presented to our clinic three days after the headaches became excessively severe. Neurological examination on admission revealed bilateral papilledema without any associated focal neurological deficits. Brain computed tomography (CT) and magnetic resonance imaging (MRI) confirmed the presence of a third ventricle colloid cyst and associated non-communicating hydrocephalus involving the lateral ventricles. As a result, the patient underwent emergency bilateral external ventricular drainage (EVD) insertion followed by a third ventricular CC excision under neuronavigation through a right frontal craniotomy. Twelve days post-operatively, the patient developed further headaches, followed by a generalized tonic-clonic seizure that led to no postictal neurological deficits. Nonetheless, computed tomography venography of the brain revealed extensive thrombosis of the superior sagittal sinus, inferior sagittal sinus, right sigmoid sinus, and right internal jugular vein. A newly diagnosed CVT was treated with intravenous heparin. The patient was discharged with warfarin, which was discontinued after 12 months. Ten years after her illness, she remained stable and free from any neurological deficits but still suffered from mild chronic headaches. Outcome: Ten years after her illness, she remained stable and free from any neurological deficits but still suffered from mild chronic headaches. Relevance: A preoperative venous study should be performed in all cases to gain a better understanding of the venous anatomy. We advocate meticulous microsurgical techniques to protect the venous system surrounding the foramen of Monro and reduce the amount of retraction during surgery.

Keywords: CVT, seizures, third ventricle colloid cyst, MRI of brain

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Authors: F. Polito, M. Cucinotta, A. Conti, C. Lo Giudice, C. Tomasello, F. Angileri, D. La Torre, M. Aguennouz

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Glioblastoma multiforme (GBM) is the most aggressive form of brain tumors, with an extremely poor prognosis. Telomeres lenght is associated with tumor progression in several type of human cancers and telomere elongation is a common molecular feature of advanced malignancies. Among the telomeric shelterin proteins PTOP is required for telomeric protein complex assembly, telomerase recruitment and activity, and telomere length regulation through a PTOP-telomerase interaction. Previous studies suggest that PTOP upregulation is involved in radioresistance and telomere lengthening in colorectal cancer cells. Moreover, in human osteosarcoma cells PTOP deletion led to telomere shortening, increased apoptosis and radiation sensitivity enhancement. However, to date, little is known about the role of PTOP in progression of glioma cancers. In light of this background aim of the study is to investigate the expression of PTOP in different grades of human glioma and its correlation with the pathological grade of gliomas, grades of malignancy, proliferative activity and apoptosis. Fifteen Low Grade Astrocytomas (LGA), 18 Anaplastic Astrocytomas (AA) and 26 Glioblastoma Multiforme (GBM) samples were analyzed. Three samples of normal brain tissue (NBT) were used as controls. The expression levels of PTOP, h-TERT, BIRC1 and cyclin D1 were determined by real time PCR and/or western blot. Results obtained shows that PTOP expression in glioma tissues is tightly correlated with clinical grade ( p < 0.01 ). No correlation was found between PTOP expression and other clinicopathologic parameters. The expression of PTOP was positively correlated with the expression of hTERT and TERF1. Furthermore PTOP positively correlates with cyclin D1 and negatively correlates with the expression of BIRC1. Our findings indicate that PTOP might play key role in the progression of glioma regulating telomerase activity and likely through regulation of cell cycle and apoptosis. In conclusion results obtained prompted us to speculate that PTOP might represents a potential molecular bio marker and a therapeutic target for the treatment of glioblastoma tumors.

Keywords: glioblastoma, PTOP, telomere, brain tumors

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Authors: Tomás Sobrino, Lara García-Varela, Marta Aramburu-Núñez, Mónica Castro, Noemí Gómez-Lado, Mariña Rodríguez-Arrizabalaga, Antía Custodia, Juan Manuel Pías-Peleteiro, José Manuel Aldrey, Daniel Romaus-Sanjurjo, Ángeles Almeida, Pablo Aguiar, Alberto Ouro

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Introduction: Alzheimer’s disease (AD) and other tauopathies are primary causes of dementia, causing progressive cognitive deterioration that entails serious repercussions for the patients' performance of daily tasks. Currently, there is no effective approach for the early diagnosis and treatment of AD and tauopathies. This study suggests a theragnostic approach based on the importance of phosphorylated tau protein (p-Tau) in the early pathophysiological processes of AD. We have developed a novel theragnostic monoclonal antibody (mAb) to provide both diagnostic and therapeutic effects. Methods/Results: We have developed a p-Tau mAb, which was doped with deferoxamine for radiolabeling with Zirconium-89 (89Zr) for PET imaging, as well as fluorescence dies for immunofluorescence assays. The p-Tau mAb was evaluated in vitro for toxicity by MTT assay, LDH activity, propidium iodide/Annexin V assay, caspase-3, and mitochondrial membrane potential (MMP) assay in both mouse endothelial cell line (bEnd.3) and cortical primary neurons cell cultures. Importantly, non-toxic effects (up to concentrations of p-Tau mAb greater than 100 ug/mL) were detected. In vivo experiments in the tauopathy model mice (PS19) show that the 89Zr-pTau-mAb and 89Zr-Fragments-pTau-mAb are stable in circulation for up to 10 days without toxic effects. However, only less than 0.2% reached the brain, so further strategies have to be designed for crossing the Brain-Blood-Barrier (BBB). Moreover, an intraparenchymal treatment strategy was carried out. The PS19 mice were operated to implement osmotic pumps (Alzet 1004) at two different times, at 4 and 7 months, to stimulate the controlled release for one month each of the B6 antibody or the IgG1 control antibody. We demonstrated that B6-treated mice maintained their motor and memory abilities significantly compared with IgG1 treatment. In addition, we observed a significant reduction in p-Tau deposits in the brain. Conclusions /Discussion: A theragnostic pTau-mAb was developed. Moreover, we demonstrated that our p-Tau mAb recognizes very-early pathology forms of p-Tau by non-invasive techniques, such as PET. In addition, p-Tau mAb has non-toxic effects, both in vitro and in vivo. Although the p-Tau mAb is stable in circulation, only 0.2% achieve the brain. However, direct intraventricular treatment significantly reduces cognitive impairment in Alzheimer's animal models, as well as the accumulation of toxic p-Tau species.

Keywords: alzheimer's disease, theragnosis, tau, PET, immunotherapy, tauopathies

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Authors: Aneta Daniel

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The subject of the study is the exploration of the origins and dynamics of the development of language studies, which have been labelled as neurolinguistics. It is worth mentioning that the origins of neurolinguistics are to be found in the research conducted by German scientists before the Second World War in Breslau Universität (presently Wroclaw). The dominant figure in these studies was professor Carl Wernicke, whose students continued and creatively developed projects of their master within this area. Professor Carl Wernicke, a German physician, anatomist, psychiatrist, and neuropathologist, is primarily known for his influential research on aphasia. His research, as well as those conducted by professor Paul Broca, has led to breakthroughs in the location of brain functions, particularly speech. Years later the theses of the pioneers of cognitive neurology (Carl Wernicke and Paul Broca) were developed by other neurolinguists. The main objective of the investigation is the reconstruction of the group of scientists –the students of Carl Wernicke– who contributed to the development of neurolinguistics. The scholars were mainly neurologists and psychiatrists and dealt with the branch of science that had not been named neurolinguistics at that time. The profiles of the scholars will be analysed and presented as the members of the group of researchers who have contributed to the breakthroughs in psychology and neuroscience. The research material consists of archival records documenting the research of professor Carl Wernicke and the researchers from Breslau (presently Wroclaw) which is one of the fastest growing cities in Europe. In 1870, when Carl Wernicke became the medical doctor, Breslau was full of cultural events: festivals and circus shows were held in the city center. Today we can come back to these events due to 'Breslauer Zeitung (1870)', which precisely describes all the events that took place on particular days. It is worth noting that those were the beginnings of antisemitism in Breslau. Many theses and articles that have survived in the libraries in Wroclaw and all over the world contribute to the development of neuroscience. The history of research on the brain and speech analysis, including the history of psychology and neuroscience, areas from which neurolinguistics is derived, will be presented.

Keywords: Aphasia, brain injury, Carl Wernicke, language, neurolinguistics

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Authors: Sonia Boscenco, Zihan Wang, Euclides José de Mendoça Filho, João Paulo Hoppe, Irina Pokhvisneva, Geoffrey B.C. Hall, Michael J. Meaney, Patricia Pelufo Silveira

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Entropy can be described as a measure of the number of states of a system, and when used in the context of physiological time-based signals, it serves as a measure of complexity. In functional connectivity data, entropy can account for the moment-to-moment variability that is neglected in traditional functional magnetic resonance imaging (fMRI) analyses. While brain fMRI resting state entropy has been associated with some pathological conditions like schizophrenia, no investigations have explored the association between brain entropy measures and individual differences in child behavior in healthy children. We describe a novel exploratory approach to evaluate brain fMRI resting state data in two child cohorts, and MAVAN (N=54, 4.5 years, 48% males) and GUSTO (N = 206, 4.5 years, 48% males) and its associations to child behavior, that can be used in future research in the context of child exposures and long-term health. Following rs-fMRI data pre-processing and Shannon entropy calculation across 32 network regions of interest to acquire 496 unique functional connections, partial correlation coefficient analysis adjusted for sex was performed to identify associations between entropy data and Strengths and Difficulties questionnaire in MAVAN and Child Behavior Checklist domains in GUSTO. Significance was set at p < 0.01, and we found eight significant associations in GUSTO. Negative associations were found between two frontoparietal regions and cerebellar posterior and oppositional defiant problems, (r = -0.212, p = 0.006) and (r = -0.200, p = 0.009). Positive associations were identified between somatic complaints and four default mode connections: salience insula (r = 0.202, p < 0.01), dorsal attention intraparietal sulcus (r = 0.231, p = 0.003), language inferior frontal gyrus (r = 0.207, p = 0.008) and language posterior superior temporal gyrus (r = 0.210, p = 0.008). Positive associations were also found between insula and frontoparietal connection and attention deficit / hyperactivity problems (r = 0.200, p < 0.01), and insula – default mode connection and pervasive developmental problems (r = 0.210, p = 0.007). In MAVAN, ten significant associations were identified. Two positive associations were found = with prosocial scores: the salience prefrontal cortex and dorsal attention connection (r = 0.474, p = 0.005) and the salience supramarginal gyrus and dorsal attention intraparietal sulcus (r = 0.447, p = 0.008). The insula and prefrontal connection were negatively associated with peer problems (r = -0.437, p < 0.01). Conduct problems were negatively associated with six separate connections, the left salience insula and right salience insula (r = -0.449, p = 0.008), left salience insula and right salience supramarginal gyrus (r = -0.512, p = 0.002), the default mode and visual network (r = -0.444, p = 0.009), dorsal attention and language network (r = -0.490, p = 0.003), and default mode and posterior parietal cortex (r = -0.546, p = 0.001). Entropy measures of resting state functional connectivity can be used to identify individual differences in brain function that are correlated with variation in behavioral problems in healthy children. Further studies applying this marker into the context of environmental exposures are warranted.

Keywords: child behaviour, functional connectivity, imaging, Shannon entropy

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Authors: Gustavo Axel Elizalde-Velázquez

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Metformin is the first line of oral therapy to treat type II diabetes and is also employed as a treatment for other indications, such as polycystic ovary syndrome, cancer, and COVID-19. Recent data suggest it is the aspirin of the 21st century due to its antioxidant and anti-aging effects. However, increasingly current articles indicate its long-term consumption generates mitochondrial impairment. Up to date, it is known metformin increases the biogenesis of Alzheimer's amyloid peptides via up-regulating BACE1 transcription, but further information related to brain damage after its consumption is missing. Bearing in mind the above, this work aimed to establish whether or not chronic exposure to metformin may alter swimming behavior and induce neurotoxicity in Danio rerio adults. For this purpose, 250 Danio rerio grown-ups were assigned to six tanks of 50 L of capacity. Four of the six systems contained 50 fish, while the remaining two had 25 fish (≈1 male:1 female ratio). Every system with 50 fish was allocated one of the three metformin treatment concentrations (1, 20, and 40 μg/L), with one system as the control treatment. Systems with 25 fish, on the other hand, were used as positive controls for acetylcholinesterase (10 μg/L of Atrazine) and oxidative stress (3 μg/L of Atrazine). After four months of exposure, a mean of 32 fish (S.D. ± 2) per group of MET treatment survived, which were used for the evaluation of behavior with the Novel Tank test. Moreover, after the behavioral assessment, we aimed to collect the blood and brains of all fish from all treatment groups. For blood collection, fish were anesthetized with an MS-222 solution (150 mg/L), while for brain gathering, fish were euthanized using the hypothermic shock method (2–4 °C). Blood was employed to determine CASP3 activity and the percentage of apoptotic cells with the TUNEL assay, and brains were used to evaluate acetylcholinesterase activity, oxidative damage, and gene expression. After chronic exposure, MET-exposed fish exhibited less swimming activity when compared to control fish. Moreover, compared with the control group, MET significantly inhibited the activity of AChE and induced oxidative damage in the brain of fish. Concerning gene expression, MET significantly upregulated the expression of Nrf1, Nrf2, BAX, p53, BACE1, APP, PSEN1, and downregulated CASP3 and CASP9. Although MET did not overexpress the CASP3 gene, we saw a meaningful rise in the activity of this enzyme in the blood of fish exposed to MET compared to the control group, which we then confirmed by a high number of apoptotic cells in the TUNEL assay. To the best of our understanding, this is the first study that delivers evidence of oxidative impairment, apoptosis, AChE alteration, and overexpression of B- amyloid-related genes in the brain of fish exposed to metformin.

Keywords: AChE inhibition, CASP3 activity, NovelTank test, oxidative damage, TUNEL assay

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Authors: Habib Alah Dadgar, Nasim Norouzbeigi

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The precise definition margin of high and low-grade gliomas is crucial for treatment. We aimed to assess the feasibility of assessment of the resection legions with post-operative positron emission tomography (PET) using [18F]O-(2-[18F]-fluoroethyl)-L-tyrosine ([18F]FET). Four patients with the suspicion of high and low-grade were enrolled. Patients underwent post-operative [18F]FET-PET, pre-operative magnetic resonance imaging (MRI) and CT for clinical evaluations. In our study, three patients had negative response to recurrence and progression and one patient indicated positive response after surgery. [18F]FET-PET revealed a legion of increased radiotracer uptake in the dura in the craniotomy site for patient 1. Corresponding to the patient history, the study was negative for recurrence of brain tumor. For patient 2, there was a lesion in the right parieto-temporal with slightly increased uptake in its posterior part with SUVmax = 3.79, so the study was negative for recurrence evaluation. In patient 3 there was no abnormal uptake with negative result for recurrence of brain tumor. Intense radiotracer uptake in the left parietal lobe where in the MRI there was a lesion with no change in enhancement in the post-contrast image is indicated in patient 4. Assessment of the resection legions in high and low-grade gliomas with [18F]FET-PET seems to be useful.

Keywords: FET-PET, CT, glioma, MRI

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Authors: Khalida Douibi, Rodrigo Balp, Solène Le Bars

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In the medical field, applications related to human experiments are frequently linked to reduced samples size, which makes the training of machine learning models quite sensitive and therefore not very robust nor generalizable. This is notably the case in Brain-Computer Interface (BCI) studies, where the sample size rarely exceeds 20 subjects or a few number of trials. To address this problem, several resampling approaches are often used during the data preparation phase, which is an overly critical step in a data science analysis process. One of the naive approaches that is usually applied by data scientists consists in the transformation of the entire database before the resampling phase. However, this can cause model’ s performance to be incorrectly estimated when making predictions on unseen data. In this paper, we explored the effect of data leakage observed during our BCI experiments for device control through the real-time classification of SSVEPs (Steady State Visually Evoked Potentials). We also studied potential ways to ensure optimal validation of the classifiers during the calibration phase to avoid overfitting. The results show that the scaling step is crucial for some algorithms, and it should be applied after the resampling phase to avoid data leackage and improve results.

Keywords: data leackage, data science, machine learning, SSVEP, BCI, overfitting

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Authors: Qian Liu, Steve Furber

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To explore how the brain may recognize objects in its general,accurate and energy-efficient manner, this paper proposes the use of a neuromorphic hardware system formed from a Dynamic Video Sensor~(DVS) silicon retina in concert with the SpiNNaker real-time Spiking Neural Network~(SNN) simulator. As a first step in the exploration on this platform a recognition system for dynamic hand postures is developed, enabling the study of the methods used in the visual pathways of the brain. Inspired by the behaviours of the primary visual cortex, Convolutional Neural Networks (CNNs) are modeled using both linear perceptrons and spiking Leaky Integrate-and-Fire (LIF) neurons. In this study's largest configuration using these approaches, a network of 74,210 neurons and 15,216,512 synapses is created and operated in real-time using 290 SpiNNaker processor cores in parallel and with 93.0% accuracy. A smaller network using only 1/10th of the resources is also created, again operating in real-time, and it is able to recognize the postures with an accuracy of around 86.4% -only 6.6% lower than the much larger system. The recognition rate of the smaller network developed on this neuromorphic system is sufficient for a successful hand posture recognition system, and demonstrates a much-improved cost to performance trade-off in its approach.

Keywords: spiking neural network (SNN), convolutional neural network (CNN), posture recognition, neuromorphic system

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Authors: Rika Susanti, Eryati Darwin, Dedi Afandi, Yanwirasti, Syahruddin Said, Noverika Windasari, Zelly Dia Rofinda

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Introduction: Blunt head trauma is one of the leading causes of death associated with murders and other deaths involved in criminal acts. Creatine kinase (CKBB) levels have been used as a biomarker for blunt head trauma. Therefore, it is now used as an alternative to an autopsy. The aim of this study is to investigate CKBB levels in cerebrospinal fluid (CSF) and post-mortem serum in order to deduce the cause and time of death. Method: This investigation was conducted through post-test–only group design involving deaths caused by blunt head trauma, which was compared to deaths caused by ketamine poisoning. Results: There were eight treatment groups, each consisting of six adult rats (Rattus norvegicus) Sprague-Dawley strain. Examinations were done at 0 hours, 1 hour, 2 hours, and 3 hours post-mortem, which followed by brain tissue observation. Data were then analyzed statistically with a repeated-measures general linear model. Conclusion: There were increases in the level of CKBB in CSF and postmortem serum in both blunt head trauma and ketamine poisoning treatment groups. However, there were no significant differences between these two groups.

Keywords: blunt head trauma, CKBB, the cause of death, estimated time of death

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Authors: Wenqiu Cao

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Suicide prevention is a global problem that needs to be taken seriously. Investigating the mechanisms of suicide in major depressive disorder (MDD) separately through neuroimaging technology is essential for effective suicide prevention. And it’s particularly urgent in geriatric depressive patients since older adults are more likely to use rapidly deadly means, and suicidal behavior is more lethal for older adults. The current study reviews five studies related to suicide in geriatric MDD that uses neuroimaging methodology in order to analyze the relevant neurobiological mechanisms. The majority of the studies found significant white matter and grey matter reduction or lesion widespread in multiple brain regions, including the frontal and parietal regions, the midbrain, the external capsule, and the cerebellum. Regarding the cognitive impairment in geriatric MDD, the reward signals were found weakened in the paralimbic cortex. The functional magnetic resonance imaging (fMRI) studies also found hemodynamic changes in the right dorsolateral prefrontal cortex (DLPFC), orbitofrontal cortex (OFC), and right frontopolar cortex (FPC) regions in late-life MDD patients with suicidal ideation. Future studies should consider the age of depression onset, more accurate measurements of suicide, larger sample size, and longitudinal design.

Keywords: brain imaging, geriatric major depressive disorder, suicidality, suicide

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Authors: Batul Kagalwala

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The nervous system is made up of complex delicate structures such as the spinal cord, peripheral nerves and the brain. These are prone to various types of injury ranging from neurodegenerative diseases to trauma leading to diseases like Parkinson's, Alzheimer's, multiple sclerosis, amyotrophic lateral sclerosis (ALS), multiple system atrophy etc. Unfortunately, because of the complicated structure of nervous system, spontaneous regeneration, repair and healing is seldom seen due to which brain damage, peripheral nerve damage and paralysis from spinal cord injury are often permanent and incapacitating. Hence, innovative and standardized approach is required for advance treatment of neurological injury. Nigella sativa (N. sativa), an annual flowering plant native to regions of southern Europe and Asia; has been suggested to have neuroprotective and anti-seizures properties. Neuroregeneration is found to occur in damaged cells when treated using extract of N. sativa. Due to its proven health benefits, lots of experiments are being conducted to extract all the benefits from the plant. The flowers are delicate and are usually pale blue and white in color with small black seeds. These seeds are the source of active components such as 30–40% fixed oils, 0.5–1.5% essential oils, pharmacologically active components containing thymoquinone (TQ), ditimoquinone (DTQ) and nigellin. In traditional medicine, this herb was identified to have healing properties and was extensively used Middle East and Far East for treating diseases such as head ache, back pain, asthma, infections, dysentery, hypertension, obesity and gastrointestinal problems. Literature studies have confirmed the extract of N. sativa seeds and TQ have inhibitory effects on inducible nitric oxide synthase and production of nitric oxide as well as anti-inflammatory and anticancer activities. Experimental investigation will be conducted to understand which ingredient of N. sativa causes neuroregeneration and roots to its healing property. An aqueous/ alcoholic extract of N. sativa will be made. Seed oil is also found to have used by researchers to prepare such extracts. For the alcoholic extracts, the seeds need to be powdered and soaked in alcohol for a period of time and the alcohol must be evaporated using rotary evaporator. For aqueous extracts, the powder must be dissolved in distilled water to obtain a pure extract. The mobile phase will be the extract while the suitable stationary phase (substance that is a good adsorbent e.g. silica gels, alumina, cellulose etc.) will be selected. Different ingredients of N. sativa will be separated using High Performance Liquid Chromatography (HPLC) for treating damaged cells. Damaged brain cells will be treated individually and in different combinations of 2 or 3 compounds for different intervals of time. The most suitable compound or a combination of compounds for the regeneration of cells will be determined using DOE methodology. Later the gene will also be determined and using Polymerase Chain Reaction (PCR) it will be replicated in a plasmid vector. This plasmid vector shall be inserted in the brain of the organism used and replicated within. The gene insertion can also be done by the gene gun method. The gene in question can be coated on a micro bullet of tungsten and bombarded in the area of interest and gene replication and coding shall be studied. Investigation on whether the gene replicates in the organism or not will be examined.

Keywords: black cumin, brain cells, damage, extract, neuroregeneration, PCR, plasmids, vectors

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Authors: Pomozova Kseniia, Gorlachev Gennadiy, Chernyaev Aleksandr, Golanov Andrey

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In clinical practice, and especially in stereotactic radiosurgery planning, the significance of diffusion-weighted imaging (DWI) is growing. This makes the existence of software capable of quickly processing and reliably visualizing diffusion data, as well as equipped with tools for their analysis in terms of different tasks. We are developing the «MRDiffusionImaging» software on the standard C++ language. The subject part has been moved to separate class libraries and can be used on various platforms. The user interface is Windows WPF (Windows Presentation Foundation), which is a technology for managing Windows applications with access to all components of the .NET 5 or .NET Framework platform ecosystem. One of the important features is the use of a declarative markup language, XAML (eXtensible Application Markup Language), with which you can conveniently create, initialize and set properties of objects with hierarchical relationships. Graphics are generated using the DirectX environment. The MRDiffusionImaging software package has been implemented for processing diffusion magnetic resonance imaging (dMRI), which allows loading and viewing images sorted by series. An algorithm for "masking" dMRI series based on T2-weighted images was developed using a deformable surface model to exclude tissues that are not related to the area of interest from the analysis. An algorithm of distortion correction using deformable image registration based on autocorrelation of local structure has been developed. Maximum voxel dimension was 1,03 ± 0,12 mm. In an elementary brain's volume, the diffusion tensor is geometrically interpreted using an ellipsoid, which is an isosurface of the probability density of a molecule's diffusion. For the first time, non-parametric intensity distributions, neighborhood correlations, and inhomogeneities are combined in one segmentation of white matter (WM), grey matter (GM), and cerebrospinal fluid (CSF) algorithm. A tool for calculating the coefficient of average diffusion and fractional anisotropy has been created, on the basis of which it is possible to build quantitative maps for solving various clinical problems. Functionality has been created that allows clustering and segmenting images to individualize the clinical volume of radiation treatment and further assess the response (Median Dice Score = 0.963 ± 0,137). White matter tracts of the brain were visualized using two algorithms: deterministic (fiber assignment by continuous tracking) and probabilistic using the Hough transform. The proposed algorithms test candidate curves in the voxel, assigning to each one a score computed from the diffusion data, and then selects the curves with the highest scores as the potential anatomical connections. White matter fibers were visualized using a Hough transform tractography algorithm. In the context of functional radiosurgery, it is possible to reduce the irradiation volume of the internal capsule receiving 12 Gy from 0,402 cc to 0,254 cc. The «MRDiffusionImaging» will improve the efficiency and accuracy of diagnostics and stereotactic radiotherapy of intracranial pathology. We develop software with integrated, intuitive support for processing, analysis, and inclusion in the process of radiotherapy planning and evaluating its results.

Keywords: diffusion-weighted imaging, medical imaging, stereotactic radiosurgery, tractography

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Authors: Hye Jin Kim, Hwa Sung Shin

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Ischemic stroke means the caused brain damage due to neurological defects, occurring occlusion of cerebral vascular resulting in thrombus or embolism. t-PA (tissue Plasminogen Activator) is the only thrombolytic agent passed the FDA (Food and Drug Administration). However, t-PA directly dissolves the thrombus (direct activity) through fibrinolysis, showing side effects such as re-occlusion. In this study, we evaluated the thrombolytic activities of the serine protease extracted from lugworms inhabiting tidal flats. The new serine protease identified as 38 kDa by SDS-PAGE was not toxic to brain endothelial cells line (hCMEC/D3). Also, the plasmin synthesis inhibition activity (indirect activity) of the new serine protease was confirmed through fibrin zymography assay and fibrin plate assay. It was higher than direct activity as compared to u-PA (urokinase Plasminogen Activator). The activities were found to be maintained at a wide range of temperature (4-70 ℃) and pH 7-10 compared to previous thrombolytic agents from the azocasein assay. In addition, the new serine protease has shown anticoagulant activity from fibrinogenolytic activity assay. In conclusion, the serine protease in lug worms inhabiting the tidal flats could be considered a promising thrombolytic candidate for the treatment of ischemic stroke.

Keywords: alkaline serine protease, bifunctional thrombolytic activity, fibrinolytic activity, ischemic stroke, lug worms

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Authors: Huan Peng, Chenye Zeng, Zhao Wang

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Alzheimer’s disease (AD) is an age-related neurodegenerative disease that is a leading cause of dementia syndromes and has become a huge burden on society and families. The main pathological features of AD involve excessive deposition of β-amyloid (Aβ) and Tau proteins in the brain, resulting in loss of neurons, expansion of neuroinflammation, and cognitive dysfunction in patients. Researchers have found effective drugs to clear the brain of error-accumulating proteins or to slow the loss of neurons, but their direct administration has key bottlenecks such as single-drug limitation, rapid blood clearance rate, impenetrable blood-brain barrier (BBB), and poor ability to target tissues and cells. Therefore, we are committed to seeking a suitable and efficient delivery system. Inspired by the possibility that exosomes may be involved in the secretion and transport mechanism of many signaling molecules or proteins in the brain, exosomes have attracted extensive attention as natural nanoscale drug carriers. We selected exosomes derived from bone marrow mesenchymal stem cells (MSC-EXO) with low immunogenicity and exosomes derived from hippocampal neurons (HT22-EXO) that may have excellent homing ability to overcome the deficiencies of oral or injectable pathways and bypass the BBB through nasal administration and evaluated their delivery ability and effect on AD. First, MSC-EXO and HT22 cells were isolated and cultured, and MSCs were identified by microimaging and flow cytometry. Then MSC-EXO and HT22-EXO were obtained by gradient centrifugation and qEV SEC separation column, and a series of physicochemical characterization were performed by transmission electron microscope, western blot, nanoparticle tracking analysis and dynamic light scattering. Next, exosomes labeled with lipophilic fluorescent dye were administered to WT mice and APP/PS1 mice to obtain fluorescence images of various organs at different times. Finally, APP/PS1 mice were administered intranasally with two exosomes 20 times over 40 days and 20 μL each time. Behavioral analysis and pathological section analysis of the hippocampus were performed after the experiment. The results showed that MSC-EXO and HT22-EXO were successfully isolated and characterized, and they had good biocompatibility. MSC-EXO showed excellent brain enrichment in APP/PS1 mice after intranasal administration, could improve the neuronal damage and reduce inflammation levels in the hippocampus of APP/PS1 mice, and the improvement effect was significantly better than HT22-EXO. However, intranasal administration of the two exosomes did not cause depression and anxious-like phenotypes in APP/PS1 mice, nor significantly improved the short-term or spatial learning and memory ability of APP/PS1 mice, and had no significant effect on the content of Aβ plaques in the hippocampus, which also meant that MSC-EXO could use their own advantages in combination with other drugs to clear Aβ plaques. The possibility of realizing highly effective non-invasive synergistic treatment for AD provides new strategies and ideas for clinical research.

Keywords: Alzheimer’s disease, exosomes derived from mesenchymal stem cell, intranasal administration, therapy-carrier dual roles

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Authors: Anthony Cogrove, Shagun Saikia, Pradeep Deshpande

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Introduction: Management of anxiety in rehabilitation setting often is a challenge and is usually done by using medication. The role of psychology and the creation of a quite environment in order to reduce stimulation helps in the process. We have a hypothesis that feedback from a calm visual imagery with soothing music help in reducing anxiety in these setting Aim-To explore the possibility of using virtual reality in the management of anxiety in a setting of neuro-rehabilitation unit. Method: Six patients in an inpatient rehabilitation unit with acquired brain injury subjected to a low stimulation calming visual motion picture with calm music. Six sessions were conducted over 6 weeks. All sessions were performed in a separate purpose built room in the unit. . A cohort of 6 people with various neurological conditions were involved in 6 sessions of 30 minutes during their inpatient rehabilitation. They reported benefit from using the virtual reality environment in reducing their anxiety. Results: All reported improvement in their anxiety levels. They felt there was a calming effect of the session. There was a sense of feeling of self empowerment on direct questioning. Conclusion: Virtual reality environment can aid the traditional rehabilitation techniques used to manage the levels of anxiety experienced by people with acquired brain injury undergoing inpatient rehabilitation.

Keywords: neurological rehabilitation, virtual reality, anxiety, calming environment

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Authors: Alaa F. A. Bakr, Sherein S. Abdelgayed, Osama. S. EL-Tawil, Adel M. Bakeer

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Objective: This study was carried out to evaluate the cytotoxic and genotoxic effect of tartrazine in both male and female albino rats. Methodology: Forty adult male (20) and female (20) Sprague Dawley albino rats (120 - 150g) were obtained and distributed into four experimental groups; Group I; 10 untreated males, Group II; 10 untreated females, Group III; 10 treated males, and Group IV; 10 treated females. Body weight was recorded weekly, reduced glutathione (RGH), lipid peroxidation (SOD), and superoxide dismutase activity (MDA) in liver tissue were carried out, histopathological studies of brain, liver, and kidneys were performed, COMET assay was performed, all values were statistically analyzed. Results: Decrease in the activity of RGH and SOD in the treated groups were reported, but there was a more significant decrease in the female treated group. MDA was increased in treated groups with tartrazine, moreover, it was more significant in the female treated group. Multiple histological lesions were developed in brain, liver, and kidneys. COMET showed positive results. Conclusion: Our study concluded that Tartrazine has a cytotoxic and genotoxic effect on albino rats and it was more significant in females than males.

Keywords: tartrazine, cytotoxicity, genotoxicity, histopathology, albino rats

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Authors: Pinhas Dannon, Aviv Weinstein

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Impulsivity is raising major interest clinically because it is associated with various clinical conditions such as delinquency, antisocial behavior, suicide attempts, aggression, and criminal activity. The evolutionary perspective argued that impulsivity relates to self-regulation and it has predicted that female individuals should have evolved a greater ability to inhibit pre-potent responses. There is supportive evidence showing that female individuals have better performance on cognitive tasks measuring impulsivity such as delay in gratification and delayed discounting mainly in childhood. During adolescence, brain imaging studies using diffusion tensor imaging on white matter architecture indicated contrary to the evolutionary perspective hypothesis, that young adolescent male individuals may be less vulnerable than age-matched female individuals to risk- and reward- related maladaptive behaviors. In adults, the results are mixed presumably owing to hormonal effects on neuro-biological mechanisms of reward. Consequently, female individuals were less impulsive than male individuals only during fertile stages of the menstrual cycle. Finally, there is evidence the serotonin (5-HT) system is more involved in the impulsivity of men than in that of women. Overall, there seem to be sex differences in impulsivity but these differences are more pronounced in childhood and they are later subject to maturational and hormonal changes during adolescence and adulthood and their effects on the brain, cognition, and behavior.

Keywords: impulse control, male population, female population, gender differences, reward, neurocognitive tests

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Authors: Maha J. Balgoon, Gehan A. Raouf, Safaa Y. Qusti, Soad S. Ali

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The main cause of Alzheimer disease (AD) was believed to be mainly due to the accumulation of free radicals owing to oxidative stress (OS) in brain tissue. The mechanism of the neurotoxicity of Aluminum chloride (AlCl3) induced AD in hippocampus Albino wister rat brain tissue, the curative & the protective effects of Lipidium sativum group (LS) water extract were assessed after 8 weeks by attenuated total reflection spectroscopy ATR-IR and histologically by light microscope. ATR-IR results revealed that the membrane phospholipid undergo free radical attacks, mediated by AlCl3, primary affects the polyunsaturated fatty acids indicated by the increased of the olefinic -C=CH sub-band area around 3012 cm-1 from the curve fitting analysis. The narrowing in the half band width(HBW) of the sνCH2 sub-band around 2852 cm-1 due to Al intoxication indicates the presence of trans form fatty acids rather than gauch rotomer. The degradation of hydrocarbon chain to shorter chain length, increasing in membrane fluidity, disorder and decreasing in lipid polarity in AlCl3 group were indicated by the detected changes in certain calculated area ratios compared to the control. Administration of LS was greatly improved these parameters compared to the AlCl3 group. Al influences the Aβ aggregation and plaque formation, which in turn interferes to and disrupts the membrane structure. The results also showed a marked increase in the β-parallel and antiparallel structure, that characterize the Aβ formation in Al-induced AD hippocampal brain tissue, indicated by the detected increase in both amide I sub-bands around 1674, 1692 cm-1. This drastic increase in Aβ formation was greatly reduced in the curative and protective groups compared to the AlCl3 group and approaches nearly the control values. These results were supported too by the light microscope. AlCl3 group showed significant marked degenerative changes in hippocampal neurons. Most cells appeared small, shrieked and deformed. Interestingly, the administration of LS in curative and protective groups markedly decreases the amount of degenerated cells compared to the non-treated group. Also the intensity of congo red stained cells was decreased. Hippocampal neurons looked more/or less similar to those of control. This study showed a promising therapeutic effect of Lipidium sativum group (LS) on AD rat model that seriously overcome the signs of oxidative stress on membrane lipid and restore the protein misfolding.

Keywords: aluminum chloride, alzheimer disease, ATR-IR, Lipidium sativum

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Authors: Naima Jannat, Ariful Islam, Sharafat Hossain

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Due to the involvement of the large target volume, Craniospinal Irradiation makes it challenging to achieve a uniform dose, and it requires different isocenters. This isocentric junction needs to shift after every five fractions to overcome the possibility of hot and cold spots. This study aims to evaluate the Planning Target Volume coverage & sparing Organ at Risk between two techniques and shows that the Field Alignment Technique does not need replanning and resetting. Planning method for Craniospinal Irradiation by Eclipse treatment planning system Field Alignment and Extended Source to Surface Distance technique was developed where 36 Gy in 20 Fraction at the rate of 1.8 Gy was prescribed. The patient was immobilized in the prone position. In the Field Alignment technique, the plan consists of half beam blocked parallel opposed cranium and a single posterior cervicospine field was developed by sharing the same isocenter, which obviates divergence matching. Further, a single field was created to treat the remaining lumbosacral spine. Matching between the inferior diverging edge of the cervicospine field and the superior diverging edge of a lumbosacral field, the field alignment option was used, which automatically matches the field edge divergence as per the field alignment rule in Eclipse Treatment Planning System where the couch was set to 2700. In the Extended Source to Surface Distance technique, two parallel opposed fields were created for the cranium, and a single posterior cervicospine field was created where the Source to Surface Distance was from 120-140 cm. Dose Volume Histograms were obtained for each organ contoured and for each technique used. In all, the patient’s maximum dose to Planning Target Volume is higher for the Extended Source to Surface Distance technique to Field Alignment technique. The dose to all surrounding structures was increased with the use of a single Extended Source to Surface Distance when compared to the Field Alignment technique. The average mean dose to Eye, Brain Steam, Kidney, Oesophagus, Heart, Liver, Lung, and Ovaries were respectively (58% & 60 %), (103% & 98%), (13% & 15%), (10% & 63%), (12% & 16%), (33% & 30%), (14% & 18%), (69% & 61%) for Field Alignment and Extended Source to Surface Distance technique. However, the clinical target volume at the spine junction site received a less homogeneous dose with the Field Alignment technique as compared to Extended Source to Surface Distance. We conclude that, although the use of a single field Extended Source to Surface Distance delivered a more homogenous, but its maximum dose is higher than the Field Alignment technique. Also, a huge advantage of the Field Alignment technique for Craniospinal Irradiation is that it doesn’t need replanning and resetting up of patients after every five fractions and 95% prescribed dose was received by more than 95% of the Planning Target Volume in all the plane with the acceptable hot spot.

Keywords: craniospinalirradiation, cranium, cervicospine, immobilize, lumbosacral spine

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Authors: Turker Yardan, Bahattin Avci, S. Sirri Bilge, Ayhan Bozkurt

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Sinapic acid (SA) is a phenylpropanoid compound with anti-inflammatory, antioxidant, and neuroprotective activities. The purpose of this study was to characterize the possible protective effect of sinapic acid on chlorpyrifos (CPF), a common organophosphorus pesticide used worldwide, induced toxicity in rats. Forty male and female rats (240-270 g) were used in this study. Each group was composed of 5 male and 5 female rats. Sinapic acid (20 mg/kg or 40 mg/kg) or vehicle (olive oil, 1 ml ⁄ rat) were given orally for 5 days. CPF (279 mg/kg) or vehicle (peanut oil, 2 ml ⁄ kg, s.c.) was administered on the sixth day, immediately after the recording of the body weight of the animals. Twenty four hours following CPF administration body weight, body temperature and locomotor activity values were recorded before decapitation of the animals. Trunk blood, brain, and liver samples were collected for biochemical examinations. Chlorpyrifos administration decreased butyrylcholinesterase activity in blood, brain, and liver, while it increased malondialdehyde (MDA) levels and advanced oxidation protein products (AOPPs) (p < 0.01 - 0.001). Additionally, CPF administration reduced the body weight, body temperature, and locomotor activity values of the animals (p < 0.01 - 0.001). All these physiological and biochemical changes induced by CPF were reduced with the 40 mg/kg dose of SA (p < 0.05 - 0.001). Our results suggest that SA administration ameliorates CPF induced toxicity in rats, possibly by supporting the antioxidant mechanism.

Keywords: antioxidant, Chlorpyrifos, poisoning, sinapic acid

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Authors: Huafeng Wei

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Failures of developing new drugs primarily based on the amyloid pathology hypothesis after decades of efforts internationally lead to changes of focus targeting alternative pathways of pathology in Alzheimer’s disease (AD). Disruption of intracellular Ca2+ homeostasis, especially the pathological and excessive Ca2+ release from the endoplasmic reticulum (ER) via ryanodine receptor (RyRs) Ca2+ channels, has been considered an upstream pathology resulting in major AD pathologies, such as amyloid and Tau pathology, mitochondria damage and inflammation, etc. Therefore, dantrolene, an inhibitor of RyRs that reduces the pathological Ca2+ release from ER and a clinically available drug for the treatment of malignant hyperthermia and muscle spasm, is expected to ameliorate AD multiple pathologies synapse and cognitive dysfunction. Our own studies indicated that dantrolene ameliorated impairment of neurogenesis and synaptogenesis in neurons developed from induced pluripotent stem cells (iPSCs) originated from skin fibroblasts of either familiar (FAD) or sporadic (SAD) AD by restoring intracellular Ca2+ homeostasis. Intranasal administration of dantrolene significantly increased its passage across the blood-brain barrier (BBB) and, therefore its brain concentrations and durations. This can render dantrolene a more effective therapeutic drug with fewer side effects for chronic AD treatment. This review summarizes the potential therapeutic and side effects of dantrolene and repurposes intranasal dantrolene as a disease-modifying drug for future AD treatment.

Keywords: Alzheimer's disease, calcium, drug development, dementia, neurodegeneration, neurogenesis

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Authors: Francesca La Rosa , Marina Saresella, Mario Clerici, Michael Heneka

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Neuroinflammation plays a key role in the modulation of the pathogenesis of neurodegenerative disorder such as Alzheimer's Disease (AD). Microglia, the main immune effector of the brain, are able to migrate to sites of Amyloid-beta (Aβ) deposition to eliminate Aβ phagocytosis upon activation by multiple receptors: Toll like receptors and scavenger receptors. The issue of whether microglia are able to eliminate pathological lesions such as neurofibrillary tangles or senile plaques from AD brain still remains the matter of controversy. Recent data suggest that the Nod Like Receptor 3 (NLRP3), multiprotein inflammasome complexes, plays a role in AD, as its activation in the microglia by Aβ triggers. IL-1β is produced as a biologically inactive pro-form and requires caspase-1 for activation and secretion. Caspase-1 activity is controlled by inflammasomes. We investigate about the importance of inflammasomes complex in the Aβ phagocytosis and its degradation. The preliminary results of phagocytosis assay and immunofluorescent experiment on primary Microglia cells to lipopolysaccharide (LPS) an Aβ exposure show that a previous treatment with LPS reduce Aβ phagocytosis. Different results were obtained in Primary Microglia wild type, NLRP3 and ASC Knockout suggesting a real inflammasomes involvement in Alzheimer's pathology. Inflammasomes inactivation reduces the production of inflammatory cytokines prolonging the protective activity of microglia and Aβ clearance, featuring a typical microglia phenotype of the early stage of AD disease.

Keywords: Alzheimer disease, innate immunity, neuroinflammation, NLRP3

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Authors: Sruthi Ramagiri, Rajeev T.

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Free radical damage has been entailed as the major culprit in the ischemic stroke contributing for oxidative damage. Recent investigations on Hydroxy Safflower Yellow A (HSYA) suggested its role in cerebral ischemia and various neurodegenerative disorders with unidentified molecular mechanisms. The current study was designed to investigate putative therapeutic role and possible molecular mechanisms of HSYA administration during the onset of reperfusion in cerebral ischemia-reperfusion (I/R) injury in cerebral stroke. Cerebral stroke was achieved by focal ischemic model. HSYA (10 mg/kg) was injected intravenously via the tail vein 5 minutes before reperfusion. Losses of sensorimotor abilities were evaluated by neurological scoring, spontaneous locomotor activity, and rotarod performance. Extent of oxidative stress was evaluated by biochemical parameters i.e., malondialdehyde (MDA), Glutathione (GSH), Super Oxide Dismutase (SOD) and catalase levels. The infarct volume of brain was assessed by 2,3,5-triphenyl tetrazolium chloride (TTC) staining technique. Increased cerebral injury (I/R) was evidenced by motor impairment, increased infarct volume and elevation of MDA levels along with significant reduction in antioxidant i.e.,MDA levels along with significant reduction in antioxidant i.e., GSH, SOD and catalase levels when compared to sham control. However, post conditioning with HSYA (10 mg/kg, i.v.) at the onset of reperfusion has significantly ameliorated sensorimotor abilities, attenuated MDA levels and reduced the infarct volume as compared with vehicle treated I/R injury group. Moreover, HSYA treatments improved antioxidant enzyme levels as compared with vehicle treated I/R-injury group. In conclusion, it may be suggested that HSYA post conditioning could be novel therapeutic approach against I/R injury in cerebral stroke possibly through its anti-oxidant mechanism.

Keywords: HSYA, Ischemia reperfusion injury, oxidative stress, stroke

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Authors: Mariane G. Tadros, Shahira M. Ezzat, Maha M. Salama, Mohamed A. Farag

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In this study, the in vitro anticholinesterase activity of the volatile oils of both O. basilicum and O. africanum was investigated and both samples showed significant activity. As a result, the major constituents of the two oils were isolated using several column chromatography. Linalool, 1,8-cineol and eugenol were isolated from the volatile oil of O. basilicum and camphor was isolated from the volatile oil of O. africanum. The anticholinesterase activity of the isolated compounds were also evaluated where 1,8-cineol showed the highest inhibitory activity followed by camphor. To confirm these activities, learning and memory enhancing effects were tested in mice. Memory impairment was induced by scopolamine, a cholinergic muscarinic receptor antagonist. Anti-amnesic effects of both volatile oils and their terpenoids were investigated by the passive avoidance task in mice. We also examined their effects on brain acetylcholinesterase activity. Results showed that scopolamine-induced cognitive dysfunction was significantly attenuated by administration of the volatile oils and their terpenoids, eugenol and camphor, in the passive avoidance task and inhibited brain acetylcholinesterase activity. These results suggest that O. basilicum and O. africanum volatile oils can be good candidates for further studies on Alzheimer’s disease via their acetylcholinesterase inhibitory actions.

Keywords: Ocimum baselicum, Ocimum africanum, GC/MS analysis, anticholinesterase

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Authors: Selina Doncevic, Lisa Perla, Angela Kindvall

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The Global War on Terror which began after September 11, 2011, increased survivability of severe injuries requiring varying trajectories of rehabilitation and recovery. The costs encompass physiologic, functional, social, emotional, psychological, vocational and scholastic domains of life. The purpose of this poster is to inform private sector health care practitioners and clinicians at various levels of the unique and long term dynamics of healthcare recovery for polytrauma, and traumatic brain injured service members and veterans in the United States of America. Challenges include care delivery between the private sector, the department of defense, and veterans affairs healthcare systems while simultaneously supporting the dynamics of acute as well as latent complications associated with severe injury and illness. Clinical relevance, subtleties of protracted recovery, and overwhelmed systems of care are discussed in the context of lessons learned and in reflection on previous wars. Additional concerns for consideration and discussion include: the cost of protracted healthcare, various U.S. healthcare payer systems, lingering community reintegration challenges, ongoing care giver support, the rise of veterans support groups and the development of private sector clinical partnerships.

Keywords: brain injury, future, polytrauma, rehabilitation

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Authors: Yung-Chih Kuo, Yung-I Lou

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Cationic solid lipid nanoparticles (CSLNs) with anti-melanotransferrin (AMT) and apolipoprotein E (ApoE) were used to carry antimitotic doxorubicin (Dox) across the blood–brain barrier (BBB) for glioblastoma multiforme (GBM) treatment. Dox-loaded CSLNs were prepared in microemulsion, grafted covalently with AMT and ApoE, and applied to human brain microvascular endothelial cells (HBMECs), human astrocytes, and U87MG cells. Experimental results revealed that an increase in the weight percentage of stearyl amine (SA) from 0% to 20% increased the size of AMT-ApoE-Dox-CSLNs. In addition, an increase in the stirring rate from 150 rpm to 450 rpm decreased the size of AMT-ApoE-Dox-CSLNs. An increase in the weight percentage of SA from 0% to 20% enhanced the zeta potential of AMT-ApoE-Dox-CSLNs. Moreover, an increase in the stirring rate from 150 rpm to 450 rpm reduced the zeta potential of AMT-ApoE-Dox-CSLNs. AMT-ApoE-Dox-CSLNs exhibited a spheroid-like geometry, a minor irregular boundary deviating from spheroid, and a somewhat distorted surface with a few zigzags and sharp angles. The encapsulation efficiency of Dox in CSLNs decreased with increasing weight percentage of Dox and the order in the encapsulation efficiency of Dox was 10% SA > 20% SA > 0% SA. However, the reverse order was true for the release rate of Dox, suggesting that AMT-ApoE-Dox-CSLNs containing 10% SA had better-sustained release characteristics. An increase in the concentration of AMT from 2.5 to 7.5 μg/mL slightly decreased the grafting efficiency of AMT and an increase in that from 7.5 to 10 μg/mL significantly decreased the grafting efficiency. Furthermore, an increase in the concentration of ApoE from 2.5 to 5 μg/mL slightly reduced the grafting efficiency of ApoE and an increase in that from 5 to 10 μg/mL significantly reduced the grafting efficiency. Also, AMT-ApoE-Dox-CSLNs at 10 μg/mL of ApoE could slightly reduce the transendothelial electrical resistance (TEER) and increase the permeability of propidium iodide (PI). An incorporation of 10 μg/mL of ApoE could reduce the TEER and increase the permeability of PI. AMT-ApoE-Dox-CSLNs at 10 μg/mL of AMT and 5-10 μg/mL of ApoE could significantly enhance the permeability of Dox across the BBB. AMT-ApoE-Dox-CSLNs did not induce serious cytotoxicity to HBMECs. The viability of HBMECs was in the following order: AMT-ApoE-Dox-CSLNs = AMT-Dox-CSLNs = Dox-CSLNs > Dox. The order in the efficacy of inhibiting U87MG cells was AMT-ApoE-Dox-CSLNs > AMT-Dox-CSLNs > Dox-CSLNs > Dox. A surface modification of AMT and ApoE could promote the delivery of AMT-ApoE-Dox-CSLNs to cross the BBB via melanotransferrin and low density lipoprotein receptor. Thus, AMT-ApoE-Dox-CSLNs have appropriate physicochemical properties and can be a potential colloidal delivery system for brain tumor chemotherapy.

Keywords: anti-melanotransferrin, apolipoprotein E, cationic catanionic solid lipid nanoparticle, doxorubicin, U87MG cells

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Authors: A. Bruce Janati, Muhammad Umair Khan, Naif Alghassab, Ibrahim Alzeir, Assem Mahmoud, M. Sammour

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Rationale: Lennox-Gastaut syndrome(LGS) is an electro-clinical syndrome composed of the triad of mental retardation, multiple seizure types, and the characteristic generalized slow spike-wave complexes in the EEG. In this article, we report on two patients with LGS whose brain MRI showed dysgenesis of corpus callosum(CC). We review the literature and stress the role of CC in the genesis of secondary bilateral synchrony(SBS). Method: This was a clinical study conducted at King Khalid Hospital. Results: The EEG was consistent with LGS in patient 1 and unilateral slow spike-wave complexes in patient 2. The MRI showed hypoplasia of the splenium of CC in patient 1, and global hypoplasia of CC combined with Joubert syndrome in patient 2. Conclusion: Based on the data, we proffer the following hypotheses: 1-Hypoplasia of CC interferes with functional integrity of this structure. 2-The genu of CC plays a pivotal role in the genesis of secondary bilateral synchrony. 3-Electrodecremental seizures in LGS emanate from pacemakers generated in the brain stem, in particular the mesencephalon projecting abnormal signals to the cortex via thalamic nuclei. 4-Unilateral slow spike-wave complexes in the context of mental retardation and multiple seizure types may represent a variant of LGS, justifying neuroimaging studies.

Keywords: EEG, Lennox-Gastaut syndrome, corpus callosum , MRI

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Authors: Saleh Mohamed, Mohamed El-Shal, Taha Kumosani, Ahmad Mal, Youssri Ahmed, Yasser Almulaiky

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The marine environment of the Jeddah southern red sea shore is subjected to increasing anthropogenic activities as sewage sludge draining and desalting processes. The objective of this study is to compare the quantitative responses of enzymatic biomarkers in fish from polluted area with the responses of organism from reference area. Enzymatic biomarkers as neurotoxic, antioxidant and detoxifying enzymes were evaluated in the brain and liver from Variola louti as a sentinel species sampled from both polluted and reference sites in the Jeddah southern red sea shore during four months January, April, July and October in 2014 and 2015. In brain of V. louti, the activity of acetylcholinestease (AChE) collected from reference area significantly increased 8.8 and 10.5 folds than that from polluted area in 2014 and 2015, respectively. The activities of catalase (CAT), glutathione reductase (GR) and glutathione peroxidase (GPx) and glutathione-S-transferase (GST) from liver of V. louti in polluted area significantly increased 1.4, 1.27 and 3, 4.5 and 4.37, 2 and 5, 4.5 folds than that from reference area in 2014 and 2015, respectively. The levels of examined enzymes are approximately similar in the four seasons detected in 2014 and 2015 indicating that the similar components of sewage were draining in red sea. In conclusion, these findings suggest the important of enzymatic biomarkers in monitoring the pollution in Jeddah red sea shore.

Keywords: Variola louti, enzymatic biomarkers, pollution, Red sea

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