Search results for: primary brain tumors

Authors: Hyuk-Hoon Kim, Young Gi Min

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Background: In carbon monoxide (CO) intoxication, the pathophysiology of delayed neurological sequelae (DNS) is very complex and remains poorly understood. And predicting whether patients who exhibit resolved acute symptoms have escaped or will experience DNS represents a very important clinical issue. Brain magnetic resonance (MR) imaging has been conducted to assess the severity of brain damage as an objective method to predict prognosis. And co-ingestion of a second poison in patients with intentional CO poisoning occurs in almost one-half of patients. Among patients with co-ingestions, 66% ingested ethanol. We assessed the effects of ethanol on neurologic sequelae prevalence in acute CO intoxication by means of abnormal lesion in brain MR. Method: This study was conducted retrospectively by collecting data for patients who visited an emergency medical center during a period of 5 years. The enrollment criteria were diagnosis of acute CO poisoning and the measurement of the serum ethanol level and history of taking a brain MR during admission period. Official readout data by radiologist are used to decide whether abnormal lesion is existed or not. The enrolled patients were divided into two groups: patients with abnormal lesion and without abnormal lesion in Brain MR. A standardized extraction using medical record was performed; Mann Whitney U test and logistic regression analysis were performed. Result: A total of 112 patients were enrolled, and 68 patients presented abnormal brain lesion on MR. The abnormal brain lesion group had lower serum ethanol level (mean, 20.14 vs 46.71 mg/dL) (p-value<0.001). In addition, univariate logistic regression analysis showed the serum ethanol level (OR, 0.99; 95% CI, 0.98 -1.00) was independently associated with the development of abnormal lesion in brain MR. Conclusion: Ethanol could have neuroprotective effect in acute CO intoxication by sedative effect in stressful situation and mitigative effect in neuro-inflammatory reaction.

Keywords: carbon monoxide, delayed neuropsychological sequelae, ethanol, intoxication, magnetic resonance

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Authors: Savaş Karpuz, Sami Küçükşen

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The aim of this study is to investigate the effectiveness of neurological rehabilitation in patients with traumatic brain injury. Participants were 45 consecutive adults with traumatic brain injury who were received the neurologic rehabilitation. Sociodemographic characteristics of the patients, the cause of the injury, the duration of the coma and posttraumatic amnesia, the length of stay in the other inpatient clinics before rehabilitation, the time between injury and admission to the rehabilitation clinic, and the length of stay in the rehabilitation clinic were recorded. The differences in functional status between admission and discharge were determined with Disability Rating Scale (DRS), Functional Independence Measure (FIM), and Functional Ambulation Scale (FAS) and levels of cognitive functioning determined with Ranchos Los Amigos Scale (RLAS). According to admission time, there was a significant improvement identified in functional status of patients who had been given the intensive in-hospital cognitive rehabilitation program. At discharge time, the statistically significant differences were obtained in DRS, FIM, FAS and RLAS scores according to admission time. Better improvement in functional status was detected in patients with lower scores in DRS, and higher scores FIM and RLAS scores at the entry time. The neurologic rehabilitation significantly affects the recovery of functional status after traumatic brain injury.

Keywords: traumatic brain injury, rehabilitation, functional status, neurological

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Authors: Paola Modesto, Floriana Fruscione, Isabella Martini, Simona Perga, Federica Riccardo, Mariateresa Camerino, Davide Giacobino, Cecilia Gola, Luca Licenziato, Elisabetta Razzuoli, Katia Varello, Lorella Maniscalco, Elena Bozzetta, Angelo Ferrari

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Canine and human melanoma, osteosarcoma (OSA), and mammary carcinomas are aggressive tumors with common characteristics making dogs a good model for comparative oncology. Novel therapeutic strategies against these tumors could be useful to both species. In humans, chondroitin sulphate proteoglycan 4 (CSPG4) is a marker involved in tumor progression and could be a candidate target for immunotherapy. The anti-CSPG4 DNA electrovaccination has shown to be an effective approach for canine malignant melanoma (CMM) [1]. An immunohistochemistry evaluation of CSPG4 expression in tumour tissue is generally performed prior to electrovaccination. To assess the possibility to perform a rapid molecular evaluation and in order to validate these spontaneous canine tumors as the model for human studies, we investigate the CSPG4 gene expression by RT qPCR in CMM, OSA, and canine mammary tumors (CMT). The total RNA was extracted from RNAlater stored tissue samples (CMM n=16; OSA n=13; CMT n=6; five paired normal tissues for CMM, five paired normal tissues for OSA and one paired normal tissue for CMT), retro-transcribed and then analyzed by duplex RT-qPCR using two different TaqMan assays for the target gene CSPG4 and the internal reference gene (RG) Ribosomal Protein S19 (RPS19). RPS19 was selected from a panel of 9 candidate RGs, according to NormFinder analysis following the protocol already described [2]. Relative expression was analyzed by CFX Maestro™ Software. Student t-test and ANOVA were performed (significance set at P<0.05). Results showed that gene expression of CSPG4 in OSA tissues is significantly increased by 3-4 folds when compared to controls. In CMT, gene expression of the target was increased from 1.5 to 19.9 folds. In melanoma, although an increasing trend was observed, no significant differences between the two groups were highlighted. Immunohistochemistry analysis of the two cancer types showed that the expression of CSPG4 within CMM is concentrated in isles of cells compared to OSA, where the distribution of positive cells is homogeneous. This evidence could explain the differences in gene expression results.CSPG4 immunohistochemistry evaluation in mammary carcinoma is in progress. The evidence of CSPG4 expression in a different type of canine tumors opens the way to the possibility of extending the CSPG4 immunotherapy marker in CMM, OSA, and CMT and may have an impact to translate this strategy modality to human oncology.

Keywords: canine melanoma, canine mammary carcinomas, canine osteosarcoma, CSPG4, gene expression, immunotherapy

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Authors: Fengjuan Wang, Azilawati Jamaludin

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Developmental Dyscalculia (DD) is defined as a particular learning difficulty with continuous challenges in learning requisite math skills that cannot be explained by intellectual disability or educational deprivation. Recent studies have increasingly recognized that DD is a heterogeneous, instead of monolithic, learning disorder with not only cognitive and behavioral deficits but so too neural dysfunction. In recent years, neuroimaging studies employed group comparison to explore the neural underpinnings of DD, which contradicted the heterogenous nature of DD and may obfuscate critical individual differences. This research aimed to investigate the neural heterogeneity of DD using case studies with functional near-infrared spectroscopy (fNIRS). A total of 54 aged 6-7 years old of children participated in this study, comprising two comprehensive cognitive assessments, an 8-minute resting state, and an 8-minute one-digit addition task. Nine children met the criteria of DD and scored at or below 85 (i.e., the 16th percentile) on the Mathematics or Math Fluency subtest of the Wechsler Individual Achievement Test, Third Edition (WIAT-III) (both subtest scores were 90 and below). The remaining 45 children formed the typically developing (TD) group. Resting-state data and brain activation in the inferior frontal gyrus (IFG), superior frontal gyrus (SFG), and intraparietal sulcus (IPS) were collected for comparison between each case and the TD group. Graph theory was used to analyze the brain network under the resting state. This theory represents the brain network as a set of nodes--brain regions—and edges—pairwise interactions across areas to reveal the architectural organizations of the nervous network. Next, a single-case methodology developed by Crawford et al. in 2010 was used to compare each case’s brain network indicators and brain activation against 45 TD children’s average data. Results showed that three out of the nine DD children displayed significant deviation from TD children’s brain indicators. Case 1 had inefficient nodal network properties. Case 2 showed inefficient brain network properties and weaker activation in the IFG and IPS areas. Case 3 displayed inefficient brain network properties with no differences in activation patterns. As a rise above, the present study was able to distill differences in architectural organizations and brain activation of DD vis-à-vis TD children using fNIRS and single-case methodology. Although DD is regarded as a heterogeneous learning difficulty, it is noted that all three cases showed lower nodal efficiency in the brain network, which may be one of the neural sources of DD. Importantly, although the current “brain norm” established for the 45 children is tentative, the results from this study provide insights not only for future work in “developmental brain norm” with reliable brain indicators but so too the viability of single-case methodology, which could be used to detect differential brain indicators of DD children for early detection and interventions.

Keywords: brain activation, brain network, case study, developmental dyscalculia, functional near-infrared spectroscopy, graph theory, neural heterogeneity

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Authors: Ozgu Hafizoglu

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Analogy is an essential tool of human cognition that enables connecting diffuse and diverse systems with attributional, deep structural, casual relations that are essential to learning, to innovation in artificial worlds, and to discovery in science. Cognitive Model of Analogy (CMA) leads and creates information pattern transfer within and between domains and disciplines in science. This paper demonstrates the Cognitive Model of Analogy (CMA) as an evolutionary approach to scientific research. The model puts forward the challenges of deep uncertainty about the future, emphasizing the need for flexibility of the system in order to enable reasoning methodology to adapt to changing conditions. In this paper, the model of analogical reasoning is created based on brain cells, their fractal, and operational forms within the system itself. Visualization techniques are used to show correspondences. Distinct phases of the problem-solving processes are divided thusly: encoding, mapping, inference, and response. The system is revealed relevant to brain activation considering each of these phases with an emphasis on achieving a better visualization of the brain cells: glial cells, axons, axon terminals, and neurons, relative to matching conditions of analogical reasoning and relational information. It’s found that encoding, mapping, inference, and response processes in four-term analogical reasoning are corresponding with the fractal and operational forms of brain cells: glial, axons, and neurons.

Keywords: analogy, analogical reasoning, cognitive model, brain and glials

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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: Hanna Poikonen, Petri Toiviainen, Mari Tervaniemi

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Event-related potentials (ERPs) evoked by simple tones in the brain have been extensively studied. However, in reality the music surrounding us is spectrally and temporally complex and dynamic. Thus, the research using natural sounds is crucial in understanding the operation of the brain in its natural environment. Music is an excellent example of natural stimulation, which, in various forms, has always been an essential part of different cultures. In addition to sensory responses, music elicits vast cognitive and emotional processes in the brain. When compared to laymen, professional musicians have stronger ERP responses in processing individual musical features in simple tone sequences, such as changes in pitch, timbre and harmony. Here we show that the ERP responses evoked by rapid changes in individual musical features are more intense in musicians than in laymen, also while listening to long excerpts of the composition Carmen. Interestingly, for professional dancers, the amplitudes of the cognitive P300 response are weaker than for musicians but still stronger than for laymen. Also, the cognitive P300 latencies of musicians are significantly shorter whereas the latencies of laymen are significantly longer. In contrast, sensory N100 do not differ in amplitude or latency between musicians and laymen. These results, acquired from a novel ERP methodology for natural music, suggest that we can take the leap of studying the brain with long pieces of natural music also with the ERP method of electroencephalography (EEG), as has already been made with functional magnetic resonance (fMRI), as these two brain imaging devices complement each other.

Keywords: electroencephalography, expertise, musical features, real-life music

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Authors: Tapas Karmaker

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Centuries ago, we came to know about ‘Golden Ratio’ also known as Golden Angle. The idea of this research is based on this theme. Researcher perceives ‘The Golden Ratio’ in terms of harmony, meaning that every single item in the universe follows a harmonic behavior. In case of human being, brain responses easily and quickly to this harmony to help memorization. In this theory, harmony means a link. This study has been carried out on a segment of school students and a segment of common people for a period of three years from 2003 to 2006. The research in this respect intended to determine the impact of harmony in the brain of these people. It has been found that students and common people can increase their memorization capacity as much as 70 times more by applying this method. This method works faster and better between age of 8 and 30 years. This result was achieved through tests to assess memorizing capacity by using tools like words, rhymes, texts, math and drawings. The research concludes that this harmonic method can be applied for improving the capacity of learning languages, for the better quality of lifestyle, or any other terms of life as well as in professional activity.

Keywords: language, education, golden brain, learning, teaching

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Authors: Paula Andrea Segura Delgado, Martha Helena Ramírez-Bahena

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Research on how the brain learns has a transcendental application in the educational context. It is crucial for teacher training to understand the nature of brain changes and their direct influence on learning processes. This communication is based on a literature review focused on neuroscience, neuroeducation, and the impact of digital technology on the human brain. Information was gathered from both English and Spanish language sources, using online journals, books and reports. The general objective was to analyze the role of neuroscience knowledge in enriching our understanding of the learning process. In fact, the authors have focused on the impact of digital technology on the human brain as well as its influence in the field of education..Neuroscience knowledge can contribute significantly to improving the training of educators and therefore educational practices. Education as an instrument of change and school as an agent of socialization, it is necessary to understand what it aims to transform: the human brain. Understanding the functioning of the human brain has important repercussions on education: this elucidates cognitive skills, psychological processes and elements that influence the learning process (memory, executive functions, emotions and the circadian cycle); helps identify psychological and neurological deficits that can impede learning processes (dyslexia, autism, hyperactivity); It allows creating environments that promote brain development and contribute to the advancement of brain capabilities in alignment with the stages of neurobiological development. The digital age presents diverse opportunities to every social environment. The frequent use of digital technology (DT) has had a significant and abrupt impact on both the cognitive abilities and physico-chemical properties of the brain, significantly influencing educational processes. Hence, educational community, with the insights from advances in neuroscience, aspire to identify the positive and negative effects of digital technology on the human brain. This knowledge helps ensure the alignment of teacher training and practices with these findings. The knowledge of neuroscience enables teachers to develop teaching methods that are aligned with the way the brain works. For example, neuroscience research has shown that digital technology is having a significant impact on the human brain (addition, anxiety, high levels of dopamine, circadian cycle disorder, decrease in attention, memory, concentration, problems with their social relationships). Therefore, it is important to understand the nature of these changes, their impact on the learning process, and how educators should effectively adapt their approaches based on these brain's changes.

Keywords: digital technology, learn process, neuroscience knowledge, neuroeducation, training proffesors

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Authors: M.R Asghari Bejestani, Gh. R. Mohammad Khani, V.R. Nafisi

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Imagined speech recognition is one of the most interesting approaches to BCI development and a lot of works have been done in this area. Many different experiments have been designed and hundreds of combinations of feature extraction methods and classifiers have been examined. Reported classification accuracies range from the chance level to more than 90%. Based on non-stationary nature of brain signals, we have introduced 3 classification modes according to time difference in inter and intra-class samples. The modes can explain the diversity of reported results and predict the range of expected classification accuracies from the brain signal accusation procedure. In this paper, a few samples are illustrated by inspecting results of some previous works.

Keywords: brain computer interface, silent talk, imagined speech, classification, signal processing

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Authors: Tiancheng Lan

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E10A is a kind of replication-defective adenovirus which carries the human endostatin gene to inhibit the growth of tumors. Kringle 5(K5) has almost the same function as angiostatin to also inhibit the growth of tumors since they are all the byproduct of the proteolytic cleavage of plasminogen. Tumor size increasing can be suppressed because both of the endostatin and K5 can restrain the angiogenesis process. Therefore, in order to improve the treatment effect on tumor, 2A peptide is used to construct a fusion gene carrying both E10A and K5. Using 2A peptide is an ideal strategy when a fusion gene is expressed because it can avoid many problems during the expression of more than one kind of protein. The overlap extension PCR is also used to connect 2A peptide with E10A and K5. The final construction of fusion gene E10A-2A-K5 can provide a possible new method of the anti-angiogenesis treatment with a better expression performance.

Keywords: E10A, Kringle 5, 2A peptide, overlap extension PCR

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Authors: Chien-Ho Lin, Ho-Ching Yang, Barbara Knowlton, Shin-Leh Huang, Ming-Chang Chiang

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Practicing motor tasks arranged in an interleaved order (interleaved practice, or IP) generally leads to better learning than practicing tasks in a repetitive order (repetitive practice, or RP), an example of how desirable difficulty during practice benefits learning. Greater difficulty during practice, e.g. IP, is associated with greater brain activity measured by higher blood-oxygen-level dependent (BOLD) signal in functional magnetic resonance imaging (fMRI) in the sensorimotor areas of the brain. In this study resting-state fMRI was applied to investigate whether increase in resting-state brain connectivity immediately after practice predicts the benefit of desirable difficulty to motor learning. 26 healthy adults (11M/15F, age = 23.3±1.3 years) practiced two sets of three sequences arranged in a repetitive or an interleaved order over 2 days, followed by a retention test on Day 5 to evaluate learning. On each practice day, fMRI data were acquired in a resting state after practice. The resting-state fMRI data was decomposed using a group-level spatial independent component analysis (ICA), yielding 9 independent components (IC) matched to the precuneus network, primary visual networks (two ICs, denoted by I and II respectively), sensorimotor networks (two ICs, denoted by I and II respectively), the right and the left frontoparietal networks, occipito-temporal network, and the frontal network. A weighted resting-state functional connectivity (wRSFC) was then defined to incorporate information from within- and between-network brain connectivity. The within-network functional connectivity between a voxel and an IC was gauged by a z-score derived from the Fisher transformation of the IC map. The between-network connectivity was derived from the cross-correlation of time courses across all possible pairs of ICs, leading to a symmetric nc x nc matrix of cross-correlation coefficients, denoted by C = (pᵢⱼ). Here pᵢⱼ is the extremum of cross-correlation between ICs i and j; nc = 9 is the number of ICs. This component-wise cross-correlation matrix C was then projected to the voxel space, with the weights for each voxel set to the z-score that represents the above within-network functional connectivity. The wRSFC map incorporates the global characteristics of brain networks measured by the between-network connectivity, and the spatial information contained in the IC maps measured by the within-network connectivity. Pearson correlation analysis revealed that greater IP-minus-RP difference in wRSFC was positively correlated with the RP-minus-IP difference in the response time on Day 5, particularly in brain regions crucial for motor learning, such as the right dorsolateral prefrontal cortex (DLPFC), and the right premotor and supplementary motor cortices. This indicates that enhanced resting brain connectivity during the early phase of memory consolidation is associated with enhanced learning following interleaved practice, and as such wRSFC could be applied as a biomarker that measures the beneficial effects of desirable difficulty on motor sequence learning.

Keywords: desirable difficulty, functional magnetic resonance imaging, independent component analysis, resting-state networks

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Authors: T. O. Ikpesu, I. Tongo, A. Ariyo

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This study was conducted to assess the effects of an organophosphate pesticide glyphosate formulation on neurological enzymes in the brain, liver and serum of juvenile Clarias gariepinus, and also to examine the antidotal prospect of Garcinia kola seeds extract. The fish divided into five groups were exposed to different treatments of glyphosate formulation and Garcinia kola seeds extract. Acetyl cholinesterase activities in the brain, liver and serum of the fish were estimated in the experimental and control fishes on day -7, 14, 21 and of 28 by spectrophotometrical methods. The enzyme was significantly (p < 0.05) inhibited in glyphosate formulation test. The inhibition percentages of AChE ranged for the brain, liver and serum between 40.7–59.4%, 50-57% and 27.5–51.3%, respectively. The aberrated parameters were recovered in G. kola seeds extract treated aquaria, and was dose and time dependent. The present study demonstrated that in vivo glyphosate formulation exposure caused AChE inhibition in the brain, liver and the serum. The brain tissue, however, might be suggested as a good indicator tissue for aquatic pollutants exposure in the fish and G. kola seeds extract has shown to be a good remedy for neurology restoration in a noxious circumstance. The findings has shown that xenobiotics could be eliminated from aquatic organisms, especially fish, and could be put into practice in areas at risk of pollutants. This approach can reduce the risks of biomagnification of poison in sea food. Hence, formulation of this plant extracts into capsule should be encouraged and supported.

Keywords: glyphosate, Clarias gariepinus, brain, Garcinia kola, acetyl cholinesterase, enzymes

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Authors: Lavanya Madhuri Bollipo, K. V. Kadambari

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Objective: To discuss key issues in the diagnosis of Parkinson disease (PD), To discuss features influencing PD progression, To discuss importance of brain SPECT data in PD diagnosis, and To discuss the essentiality of machine learning techniques in early diagnosis of PD. An accurate and early diagnosis of PD is nowadays a challenge as clinical symptoms in PD arise only when there is more than 60% loss of dopaminergic neurons. So far there are no laboratory tests for the diagnosis of PD, causing a high rate of misdiagnosis especially when the disease is in the early stages. Recent neuroimaging studies with brain SPECT using 123I-Ioflupane (DaTSCAN) as radiotracer shown to be widely used to assist the diagnosis of PD even in its early stages. Machine learning techniques can be used in combination with image analysis procedures to develop computer-aided diagnosis (CAD) systems for PD. This paper addressed recent studies involving diagnosis of PD in its early stages using brain SPECT data with Machine Learning Techniques.

Keywords: Parkinson disease (PD), dopamine transporter, single-photon emission computed tomography (SPECT), support vector machine (SVM)

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Authors: Amedeo D'Angiulli, Kylie Schibli

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Traditionally, children’s brain development research has emphasized the limitative aspects of disability and impairment, electing as an explanatory model the classical clinical notions of brain lesion or functional deficit. In contrast, Positive Educational Neuroscience (PEN) is a new approach that emphasizes strengths and human flourishing related to the brain by exploring how learning practices have the potential to enhance neurocognitive flexibility through neuroplastic overcompensation. This mini-review provides an overview of PEN and shows how it links to the concept of neurocognitive flexibility. We provide examples of how the present concept of neurocognitive flexibility can be applied to special education by exploring examples of neuroplasticity in the learning domain, including: (1) learning to draw in congenitally totally blind children, and (2) music training in children from disadvantaged neighborhoods. PEN encourages educators to focus on children’s strengths by recognizing the brain’s capacity for positive change and to incorporate activities that support children’s individual development.

Keywords: neurocognitive development, positive educational neuroscience, sociocultural approach, special education

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Authors: Mir Jalil Razavi, Tianming Liu, Xianqiao Wang

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Cortical folding, characterized by convex gyri and concave sulci, has an intrinsic relationship to the brain’s functional organization. Understanding the mechanism of the brain’s convoluted patterns can provide useful clues into normal and pathological brain function. During the development, the cerebral cortex experiences a noticeable expansion in volume and surface area accompanied by tremendous tissue folding which may be attributed to many possible factors. Despite decades of endeavors, the fundamental mechanism and key regulators of this crucial process remain incompletely understood. Therefore, to taking even a small role in unraveling of brain folding mystery, we present a mechanical model to find mechanism of 3-hinges formation in a growing brain that it has not been addressed before. A 3-hinge is defined as a gyral region where three gyral crests (hinge-lines) join. The reasons that how and why brain prefers to develop 3-hinges have not been answered very well. Therefore, we offer a theoretical and computational explanation to mechanism of 3-hinges formation in a growing brain and validate it by experimental observations. In theoretical approach, the dynamic behavior of brain tissue is examined and described with the aid of a large strain and nonlinear constitutive model. Derived constitute model is used in the computational model to define material behavior. Since the theoretical approach cannot predict the evolution of cortical complex convolution after instability, non-linear finite element models are employed to study the 3-hinges formation and secondary morphological folds of the developing brain. Three-dimensional (3D) finite element analyses on a multi-layer soft tissue model which mimics a small piece of the brain are performed to investigate the fundamental mechanism of consistent hinge formation in the cortical folding. Results show that after certain amount growth of cortex, mechanical model starts to be unstable and then by formation of creases enters to a new configuration with lower strain energy. By further growth of the model, formed shallow creases start to form convoluted patterns and then develop 3-hinge patterns. Simulation results related to 3-hinges in models show good agreement with experimental observations from macaque, chimpanzee and human brain images. These results have great potential to reveal fundamental principles of brain architecture and to produce a unified theoretical framework that convincingly explains the intrinsic relationship between cortical folding and 3-hinges formation. This achieved fundamental understanding of the intrinsic relationship between cortical folding and 3-hinges formation would potentially shed new insights into the diagnosis of many brain disorders such as schizophrenia, autism, lissencephaly and polymicrogyria.

Keywords: brain, cortical folding, finite element, three hinge

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Authors: Mannan Malik Muhammad Naeem, Jeong Myung Yung

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Functional near infrared spectroscopy (fNIRS) has a favorable position in non-invasive brain imaging techniques. The concentration change of oxygenated hemoglobin and de-oxygenated hemoglobin during particular cognitive activity is the basis for this neuro-imaging modality. Two wavelengths of near-infrared light can be used with modified Beer-Lambert law to explain the indirect status of neuronal activity inside brain. The temporal resolution of fNIRS is very good for real-time brain computer-interface applications. The portability, low cost and an acceptable temporal resolution of fNIRS put it on a better position in neuro-imaging modalities. In this study, an optimization model for impulse response function has been used to estimate/predict initial dip using fNIRS data. In addition, the activity strength parameter related to motor based cognitive task has been analyzed. We found an initial dip that remains around 200-300 millisecond and better localize neural activity.

Keywords: fNIRS, brain-computer interface, optimization algorithm, adaptive signal processing

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Authors: Nicole Selvi Hill, Archchana Radhakrishnan

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Introduction: Traumatic brain injury (TBI) is a leading cause of mortality among trauma patients. In the management of TBI, the main principle is avoiding cerebral ischemia, as this is a strong determiner of neurological outcomes. The use of vasoactive drugs, such as vasopressin, has an important role in maintaining cerebral perfusion pressure to prevent secondary brain injury. Current guidelines do not suggest a preferred vasoactive drug to administer in the management of TBI, and there is a paucity of information on the therapeutic potential of vasopressin following TBI. Vasopressin is also an endogenous anti-diuretic hormone (AVP), and pathways mediated by AVP play a large role in the underlying pathological processes of TBI. This creates an overlap of discussion regarding the therapeutic potential of vasopressin following TBI. Currently, its popularity lies in vasodilatory and cardiogenic shock in the intensive care setting, with increasing support for its use in haemorrhagic and septic shock. Methodology: This is a review article based on a literature review. An electronic search was conducted via PubMed, Cochrane, EMBASE, and Google Scholar. The aim was to identify clinical studies looking at the therapeutic administration of vasopressin in severe traumatic brain injury. The primary aim was to look at the neurological outcome of patients. The secondary aim was to look at surrogate markers of cerebral perfusion measurements, such as cerebral perfusion pressure, cerebral oxygenation, and cerebral blood flow. Results: Eight papers were included in the final number. Three were animal studies; five were human studies, comprised of three case reports, one retrospective review of data, and one randomised control trial. All animal studies demonstrated the benefits of vasopressors in TBI management. One animal study showed the superiority of vasopressin in reducing intracranial pressure and increasing cerebral oxygenation over a catecholaminergic vasopressor, phenylephrine. All three human case reports were supportive of vasopressin as a rescue therapy in catecholaminergic-resistant hypotension. The retrospective review found vasopressin did not increase cerebral oedema in TBI patients compared to catecholaminergic vasopressors; and demonstrated a significant reduction in the requirements of hyperosmolar therapy in patients that received vasopressin. The randomised control trial results showed no significant differences in primary and secondary outcomes between TBI patients receiving vasopressin versus those receiving catecholaminergic vasopressors. Apart from the randomised control trial, the studies included are of low-level evidence. Conclusion: Studies favour vasopressin within certain parameters of cerebral function compared to control groups. However, the neurological outcomes of patient groups are not known, and animal study results are difficult to extrapolate to humans. It cannot be said with certainty whether vasopressin’s benefits stand above usage of other vasoactive drugs due to the weaknesses of the evidence. Further randomised control trials, which are larger, standardised, and rigorous, are required to improve knowledge in this field.

Keywords: catecholamines, cerebral perfusion pressure, traumatic brain injury, vasopressin, vasopressors

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Authors: Shangerganesh Lingeshwaran

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In this presentation, we have performed numerical simulations for a reaction-diffusion equation with various nonlinear density-dependent diffusion operators and proliferation functions. The mathematical model represented by parabolic partial differential equation is considered to study the invasion of gliomas (the most common type of brain tumors) and to describe the growth of cancer cells and response to their treatment. The unknown quantity of the given reaction-diffusion equation is the density of cancer cells and the mathematical model based on the proliferation and migration of glioma cells. A standard Galerkin finite element method is used to perform the numerical simulations of the given model. Finally, important observations on the each of nonlinear diffusion functions and proliferation functions are presented with the help of computational results.

Keywords: glioma invasion, nonlinear diffusion, reaction-diffusion, finite eleament method

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Authors: M. S. Hasni, J. Guan, K. Yakimchuk, M. Berglund, B. Sander, G. Enblad, R. M. Amini, S. Okret

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Lymphomas are generally not considered as endocrine-related cancers. However, most lymphoid malignancies show gender differences in incidence and show prognosis with males being more affected. Furthermore, some epidemiological data indicate a protective role of estrogens against Non-Hodgkin lymphomas. Recent studies have demonstrated estrogen receptor β (ERβ) to be the major ER expressed in normal and malignant cells of lymphoid origin. We have analyzed the effects of estradiol and selective ERα and ERβ agonists on lymphoma growth in culture and in vivo. Treating lymphoma cells with estradiol or ERα selective agonist had minor or no effect on cell growth while selective ERβ agonist treatment showed an antiproliferative effect. When grafting mice with murine T lymphoma cells, male mice developed larger tumors compared to female mice, a difference that was abolished following ovariectomy, demonstrating estrogen-dependent growth in vivo. When subcutaneously grafting lymphoma cells to mice, so far growth of all tested human B lymphoma tumors (Raji and Ramos Burkitt lymphoma, SU.DHL4 (GC) and U2932 (ABC) DLBCL, Granta-519, Maver1 and Z138 MCL cells), were reduced following treatment with ERβ selective agonist (ref. 2 and unpublished). Moreover, the number and size of liver foci of disseminating Raji cells was reduced. We have identified target genes and mechanism that could explain the above effects of ERβ agonists. This included effects on angio and lymphangiogenesis. Now we have further analyzed effects of ERβ agonists on Ibrutinib-sensitive and -insensitive MCL cells in xenograft experiments as well as ERβ expression in primary lymphoma material (DLBCL). Preliminary statistical analysis has been done correlating ERβ expression to other biomarkers and clinical data.

Keywords: lymphomas, estrogen receptors, cancer, liver foci

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Authors: Rasime Kalkan, Emine Ikbal Atli, Ali Arslantaş, Muhsin Özdemir, Sevilhan Artan

Abstract:

Glioblastoma (WHO grade IV), is the malignant form of brain tumor, the genetic background of the GBM is highly variable. The tumor mass of a GBM is multilayered and every tumor layer shows distinct characteristics with a different cell population. The treatment planning of GBM should be focused on the tumor genetic characteristics. We screened primary glioblastoma multiforme (GBM) in a population-based study for MGMT and RARβ methylation and IDH1 mutation correlated them with clinical data and treatment. There was no correlation between MGMT-promoter methylation and overall survival. The overall survival time of the patients with methylated RARβ was statically (OS;p<0,05) significance between the patients who were treated with chemotherapy and radiotherapy. Here we showed the status of IDH1 gene associatied with younger age. We demonstrated that the together with MGMT gene the RARβ gene should be used as a potantial treatment decision marker for GBMs.

Keywords: RARβ, primary glioblastoma multiforme, methylation, MGMT

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Authors: Elham Ahmadi, Mehrdad Ravanshad, Joyce Fingeroth, Mazyar Ziyaeyan, Rajesh Panigrahi, Jun Xie, Gao Guangping

Abstract:

B-cell proliferative disorders often occur among persons that are T-cell compromised. These disorders are primarily EBV+ and can first present with a focal lesion. Direct introduction of oncolytic viruses into localized tumors provides theoretical advantages over chemotherapy and immunotherapy by reducing systemic toxicity, to which the immunocompromised host is most vulnerable. Widely studied as a vehicle for gene therapy, AAV has only rarely been applied to treat cancer. As a prelude to development of a therapeutic vehicle, we assessed the ability of 15 distinct recombinant AAV serotypes (rAAV1, rAAV2, rAAV3b, rAAV4, rAAV5, rAAV6, rAAV6.2, rAAV6TM, rAAV7, rAAV8, rAAVrh8, rAAV9, rAAVrh10, rAAV39, rAAV43) bearing eGFP to infect human B-cell tumor lines compared with primary B-cells in vitro. Enhanced infection of tumor lines by AAV 6.2 was demonstrated by flow cytometry. EBV superinfection of EBV negative B-cell tumor lines increased susceptibility to AAV6.2 infection. As proof of concept, AAV6.2 bearing HSV-1 thymidine kinase in place of eGFP eliminated tumor cells upon exposure to ganciclovir.

Keywords: AAV, gene therapy, lymphoma, malignancy, tropism

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Authors: André Furtado, Rafael Mineiro, Isabel Gonçalves, Cecília Santos, Telma Quintela

Abstract:

The development of therapies for central nervous system (CNS) disorders is one of the biggest challenges of current pharmacology, given the unique features of brain barriers, which limit drug delivery. Efflux transporters (ABC transporters) expressed at the blood-cerebrospinal fluid barrier (BCSFB), are the main obstacles for the delivery of therapeutic compounds into the CNS, compromising the effective treatment of brain cancer, brain metastasis from peripheral cancers, or even neurodegenerative disorders. It is thus extremely important to understand the regulation of these transporters for reducing their expression while treating a brain disorder or choosing the most appropriate conditions for drug administration. Based on the fact that the BCSFB have fine-tuned biological rhythms, studying the circadian variation of drug transport processes is critical for choosing the most appropriate time of the day for drug administration. In our study, using an in vitro model of the BCSFB, we characterized the circadian transport profile of methotrexate (MTX) and donepezil (DNPZ), two drugs involved in the treatment of cancer and Alzheimer’s Disease symptoms, respectively. We found that MTX is transported across the basal and apical membranes of the BCSFB in a circadian way. The circadian pattern of an ABC transporter, Abcc4, might be partially responsible for MTX circadian transport. Furthermore, regarding the DNPZ transport study, we observed that the regulation of Abcg2 expression by the circadian rhythm will impact the circadian-dependent transport of DNPZ across the BCSFB. Overall, our results will contribute to the current knowledge on brain pharmacoresistance at the BCSFB by disclosing how circadian rhythms control drug delivery to the brain, setting the grounds for a potential application of chronotherapy to brain diseases to enhance the efficacy of medications and minimize their side effects.

Keywords: blood-cerebrospinal fluid barrier, ABC transporters, drug transport, chronotherapy

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Authors: M. R. Akbari, M. Sadeghi, R. Faghihi, M. A. Mosleh-Shirazi, A. R. Khorrami-Moghadam

Abstract:

Proton radiotherapy (PRT) is becoming an established treatment modality for cancer. The localized tumors, the same as undifferentiated thyroid tumors are insufficiently handled by conventional radiotherapy, while protons would propose the prospect of increasing the tumor dose without exceeding the tolerance of the surrounding healthy tissues. In spite of relatively high advantages in giving localized radiation dose to the tumor region, in proton therapy, secondary neutron production can have significant contribution on integral dose and lessen advantages of this modality contrast to conventional radiotherapy techniques. Furthermore, neutrons have high quality factor, therefore, even a small physical dose can cause considerable biological effects. Measuring of this neutron dose is a very critical step in prediction of secondary cancer incidence. It has been found that FLUKA Monte Carlo code simulations have been used to evaluate dose due to secondaries in proton therapy. In this study, first, by validating simulated proton beam range in water phantom with CSDA range from NIST for the studied proton energy range (34-54 MeV), a proton therapy in thyroid gland cancer was simulated using FLUKA code. Secondary neutron dose equivalent of some organs and tissues after the target volume caused by 34 and 54 MeV proton interactions were calculated in order to evaluate secondary cancer incidence. A multilayer cylindrical neck phantom considering all the layers of neck tissues and a proton beam impinging normally on the phantom were also simulated. Trachea (accompanied by Larynx) had the greatest dose equivalent (1.24×10-1 and 1.45 pSv per primary 34 and 54 MeV protons, respectively) among the simulated tissues after the target volume in the neck region.

Keywords: FLUKA code, neutron dose equivalent, proton therapy, thyroid gland

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Authors: Akhtar Aman, Abida Raza, Shumaila Bashir, Javaid Irfan, Andreas G. Schätzlein, Ijeoma F Uchegbeu

Abstract:

Development of efficient delivery system for hydrophobic drugs remains a major concern in chemotherapy. The objective of the current study was to develop polymeric drug-delivery system for etoposide from amphiphilic derivatives of glycol chitosan, capable to improve the pharmacokinetics and to reduce the adverse effects of etoposide due to various organic solvents used in commercial formulations for solubilisation of etoposide. As a promising carrier, amphiphilic derivatives of glycol chitosan were synthesized by chemical grafting of palmitic acid N-hydroxy succinimide and quaternisation to glycol chitosan backbone. To this end a 7.9 kDa glycol chitosan was modified by palmitoylation and quaternisation into 13 kDa. Nano sized micelles prepared from this amphiphilic polymer had the capability to encapsulate up to 3 mg/ml etoposide. The pharmacokinetic results indicated that GCPQ based etoposide formulation transformed the biodistribution pattern. AUC 0.5-24 hr showed statistically significant difference in ETP-GCPQ vs. commercial preparation in liver (25 vs 70, p<0.001), spleen (27 vs. 36, P<0.05), lungs (42 vs. 136, p<0.001), kidneys (25 vs. 30, p<0.05) and brain (19 vs. 9,p<0.001). Using the hydrophobic fluorescent dye Nile red, we showed that micelles efficiently delivered their payload to MCF7 and A2780 cancer cells in-vitro and to A431 xenograft tumor in-vivo, suggesting these systems could deliver hydrophobic anti- cancer drugs such as etoposide to tumors. The pharmacokinetic results indicated that the GCPQ micelles transformed the biodistribution pattern and increased etoposide concentration in the brain significantly compared to free drug after intravenous administration. GCPQ based formulations not only reduced side effects associated with current available formulations but also increased their transport through the biological barriers, thus making it a good delivery system.

Keywords: glycol chitosan, Nile red, micelles, etoposide, A431 xenografts

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Authors: Shelly Sharma, Pooja Chadha

Abstract:

Humans are exposed to pesticides and insecticides either directly or indirectly. Exposure to these pesticides may lead to acute toxicity to mammals and non-target organisms. Chlorpyrifos (CPF) is a broad spectrum organophosphate pesticide widely used in various countries of the world. The aim of the present study was to assess the toxicity associated with chlorpyrifos exposure and possible mitigating effect of cow urine against genotoxic and toxic effects in rat brain induced by chlorpyrifos. For this purpose LD50 was determined and rats were orally administered with 1/8th of LD50 (19mg/kg b.wt). Brain samples were taken after 24hrs, 48hrs and 72hrs of treatment. A significant increase in the % tail DNA was observed along with the increase in MDA levels of brain tissues in chlorpyrifos treated groups as compared to control. Cow urine treated groups show decrease in DNA damage and MDA levels as compared to CPF treated group. The study indicates that cow urine has ameliorative potential against neurotoxicity and genotoxicity induced by CPF. Cow urine is considered rich in vitamin A, E and volatile fatty acids which provide antioxidant potential to it. Thus, it can be used as a genoprotective agent.

Keywords: comet assay, brain, cow urine, genotoxicity, toxicity

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Authors: Zahra F. Al-Khateeb, Shenel Shekerzade, Hasna Boumenar, Siân M. Henson, Jordi L. Tremoleda, A. T. Michael-Titus

Abstract:

Traumatic brain injury (TBI) is the leading cause of disability and death in young adults and also increases the risk ofneurodegeneration. The mechanisms linking moderate to severe TBI to neurodegeneration are not known. It has been proposed that cellular senescence inductionpost-injury could amplify neuroinflammation and induce long-term changes. The impact of these processes after injury to an immature brain has not been characterised yet. We carried out a controlled cortical impact injury (CCI) in juvenile 1 month-old male CD1 mice. Animals were anesthetised and received a unilateral CCI injury. The sham group received anaesthesia and had a craniotomy. A naïve group had no intervention. The brain tissue was analysed at 5 days and 35 days post-injury using immunohistochemistry and markers for microglia, astrocytes, and senescence. Compared tonaïve animals, injured mice showed an increased microglial and astrocytic reaction early post-injury, as reflected in Iba1 and GFAP markers, respectively; the GFAP increase persisted in the later phase. The senescence analysis showed a significant increase inγH2AX-53BP1 nuclear foci, 8-oxoguanine, p19ARF, p16INK4a, and p53 expression in naïve vs. sham groups and naïve vs. CCI groups, at 5 dpi. At 35 days, the difference was no longer statistically significant in all markers. The injury induced a decrease p21 expression vs. the naïve group, at 35 dpi. These results indicate the induction of a complex senescence response after immature brain injury. Some changes occur early and may reflect the activation/proliferation of non-neuronal cells post-injury that had been hindered, whereas changes such as p21 downregulation may reflect a delayed response and pro-repair processes.

Keywords: cellular senescence, traumatic brain injury, brain injury, controlled cortical impact

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Authors: Harry G. Segal

Abstract:

The idea of the “self” has been essential ever since the early modern period in western culture, especially since the development of psychotherapy, but advances in neuroscience and cognitive theory challenge traditional notions of the self. More specifically, neuroanatomists have found no location of “the self” in the brain; instead, consciousness has been posited to be a rapid combination of perception, memory, anticipation of future events, and judgment. In this paper, a theoretical model is presented to address these neuroanatomical findings and to revise the historical understanding of “selfhood” in the practice of psychotherapy.

Keywords: the self, psychotherapy, the self and the brain

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Authors: Radek Novotný, Martina Maněnová

Abstract:

This article presents a summary of reviews on gender differences in perception of information and communication technology (ICT) by pupils in primary education. The article outlines the meaning of ICT in primary education then summarizes different studies of the use of ICT in primary education from the point of view of gender. The article also presents the specific differences of gender in the knowledge of modalities of use of specialized digital tools and the perception and value assigned to ICT, accordingly the article provides insight into the background of gender differences in performance in relation to ICT to determinate the complex meaning of pupils attitudes to the ICT.

Keywords: ICT in primary education, attitudes to ICT, gender differences, gender and ICT

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Authors: Yung-Chih Kuo, I-Hsuan Lee

Abstract:

Solid lipid nanoparticles (SLNs) conjugated with aprotinin (Apr) and melanotransferrin antibody (Anti-MTf) were used to carry doxorubicin (Dox) across the blood–brain barrier (BBB) for glioblastoma multiforme (GBM) chemotherapy. Dox-entrapped SLNs with grafted Apr and Anti-MTf (Apr-Anti-MTf-Dox-SLNs) were applied to a cultured monolayer comprising human brain-microvascular endothelial cells (HBMECs) with regulation of human astrocyte (HAs) and to a proliferated colony of U87MG cells. Based on the average particle diameter, zeta potential, entrapping efficiency of Dox, and grafting efficiency of Apr and Anti-MTf, we found that 40% (w/w) 1,2-dipalmitoyl-sn-glycero-3-phosphocholine in lipids were appropriate for fabricating Apr-Anti-MTf-Dox-SLNs. In addition, Apr-Anti-MTf-Dox-SLNs could prevent Dox from fast dissolution and did not induce a serious cytotoxicity to HBMECs and HAs when compared with free Dox. Moreover, the treatments with Apr-Anti-MTf-Dox-SLNs enhanced the ability of Dox to infuse the BBB and to inhibit the growth of GBM. The current Apr-Anti-MTf-Dox-SLNs can be a promising pharmacotherapeutic preparation to penetrate the BBB for malignant brain tumor treatment.

Keywords: solid lipid nanoparticle, glioblastoma multiforme, blood–brain barrier, doxorubicin

Procedia PDF Downloads 362