Department of Neurosciences Universiti Sains Malaysia
The Department Of Neurosciences, Universiti Sains Malaysia (Science University of Malaysia) was established in 2004, beginning as a unit in 1996. Under the leadership of Professor Dr. Jafri Malin Abdullah, MD, Dip. Cert. Spec. Neurosurgery, University of Ghent, Belgium, PhD, FACS, FRCS (Ed), FWFNS, FICS, its vision is to gain advancement in the understanding of brain disorders with implications for treatment and rehabilitation.
The department is actively involved in various basic as well as applied clinical sciences research. In February 2006, it inaugurated the Neuroscience Research and Teaching Laboratory. The Palm Laser Micro-dissection and Laser Scanning Microscope and the Patch Clamp System are some of the newly acquired equipment.
Major research interests include evaluation of the neuro-therapeutic potential of indigenous plant sciences, neurogenetics, cell culture, epilepsy, cerebrovascular disorders, brain tumours, vaccines as well as behavioural neurology.
Research
Evaluation of extracts of two species of sea cucumber in regenerating astrocytes after mechanically induced injury of the basal ganglia
Glial scar consists of reactive astrocytes and proteoglycans. In this study, we are interested in the investigation of reactive astrocytes (reactive gliosis) which creates a barrier in CNS regeneration. The marker that we are looking for is the Palladin expression on reactive astrocytes. Palladin is rapidly and persistently upregulated in astrocytes in response to injury in vivo and in vitro studies. If we can reduce the expression of Palladin, the reactive astrocytes will decrease in number, allowing the CNS regeneration to occur. To achieve this, the healing properties of two species of Sea Cucumber extracts will be investigated in terms of the reduction of the formation of glial.
Acceptability of hippocampal isografts transplants in rat’s brain with basal ganglia lesions: an immunohistochemistry and electron microscopy analysis
The neural organ consists of brain, spinal cord, eye, and peripheral ganglia that comprise a wide variety of different cell types. There are neuronal, glial, endothelial, epithelial, connective, stem and other cell elements. Glial cells can be astroglia, oligodendroglia, or microglia in the central nervous system or schwann cells in the peripheral nervous system. Each neuronal and glial cell type can be further subdivided into subtypes based on anatomical location, developmental age, and the repertoire of genes expressed. The most important unit is the astrocyte which bridges all neurons and functions as the “engine” of the brain. Current tissues that were used were mainly from embryonic tissues , xenografts especially from porcine and tumor cells like teratocarcinoma of the testes. It is believed that cells from the same species may be useful for the purpose of treatment of strokes, dementia or movement disorders which involves the basal ganglia lesion.
Isografts transplants of Schwann cells in a paraplegic rat spinal cord model: immunohistochemistry and electron microscopy analysis
Paraplegia is a permanent paralysis of the body caused by injury or disease affecting the spinal cord. It involves a loss of sensation and movement in the legs and in part or the entire trunk. Despite intensive experimental research and recent advancements in bio-technology and re-engineering, no cure has been found in the treatment of complete spinal cord lesions. The incidence of traumatic paraplegia due to spinal cord injury in Malaysia is high Schwann cells naturally support axonal regeneration after injury in the peripheral nervous system, and have also shown a significant, albeit limited, ability to support axonal growth and remyelination after grafting to the central nervous system (CNS).
Apolipoprotein E and Outcome in Hemorrhagic Stroke: A preliminary study
Apolipoprotein E is a polymorphic glycoprotein produced in different cells that plays a role in cholesterol transport and the mechanisms of lipoprotein metabolism. The possible association between the apolipoprotein E gene, metabolic regulation of cholesterol and the outcome of patient after suffering hemorrhagic stroke was investigated. A prospective cohort study was conducted on all patients with hemorrhagic stroke admitted to the Hospital Universiti Sains Malaysia during a 1-year period. All patients were managed according to standard protocol, and treatments were given according to their clinical grading. The study end points were survival time and functional outcome at 6 months based on a dichotomized Glasgow Outcome Scale (GOS). Thirty-six patients were recruited. 27 (75%) patients had Glasgow Coma Scale (GCS) between 5 to 8 on admission and 9 (25%) were admitted with GCS of 9. At 6 months, 86% had a poor or unfavorable outcome (GOS I-III) and 14% had good or favorable outcome (GOS IV-V). The mortality rate at 6 months were 55%. The univariate analysis for survival function revealed the midline shift ( p=0.0064 ) and pupillary status on admission ( p=0.0016 ) were significant predictors. Multivariate analysis identified midline shift as the single predictor of functional outcome ( p=0.013 ), and the papillary status was sole significant predictor of survival function ( p=0.016 ). Apolipoprotein E epsilon 4 was not found in all of the samples. In our study high levels of total cholesterol and LDL-C which accepted risk factors for hemorrhagic stroke, were more frequent in patients than in the healthy control. Gene-gene and polymorphism-polymorphism interactions must be explored to understand and underlying functional basis for the relationships discovered. Studies of multiple genes are needed, rather than the single gene studies currently available. The larger prospective studies looking at larger panels of gene polymorphisms are required.
Newcastle Disease Virus Research
Viruses with inherent oncolytic activities have been investigated as virotherapy, an alternative approach in cancer treatment in humans. NDV AF2240 and V4UPM are two of the several strains isolated in Malaysia. These strains showed significant oncolytic effects on breast and colon cancer as well as leukemia. As shown in some studies, the use of NDV in high dosage has been exhibited to be effective against non-responsive grade IV glioblastoma. The in vivo research involves the transduction of a gene capable of producing green fluorescent protein (GFP) in human cancer cells. These fluorescent cancer cells are implanted into the brain of [...] mice and under a blue light, the said gene will cause the cells to emit a green glow, enabling the researcher to monitor the behaviour of the cells.
Mutational screening and protein expression analysis of p27 and cyclin D1 genes in gliomas and meningiomas
Gliomas and meningiomas are the two most commonly reported types of brain tumors. Current therapeutic approaches for malignant gliomas are surgery, chemotherapy and radiotherapy. Alhough advances in these therapeutic modalities have been made, survivality of the patients remain low, less than one year. Meningioma, though classified as benign still accounts for about 20% of significant patients’ morbidity and mortality.
Our study focused on the involvement of p27 and cyclin D1 genes in the glioma and meningioma development. In determining the molecular genetic abnormalities of both markers, we found no significant correlation of neither p27 nor cyclin D1 in the glioma and meningioma progression. However, protein expression analysis showed that level of p27 protein was elucidated in both gliomas and meningiomas. Increment of p27 protein as the tumor suppressor gene did not show to restrain the progression of the cancer cells. We subsequently correlated that mislocalization of the protein into cytoplasm was the factor which contributed to the dysfunction of the protein. In addition, protein expression analysis of cyclin D1 showed that the protein expression decreased in higher grades of brain tumors. Since cyclin D1 is one of the important machinery which controls the cell cycle progression, we believe that other abnormalities allow the cancer cells to uncontrollably proliferate. To further prove the hypothesis, supplementary research need to be carried out.
Comparison of Potential Antiepileptic Bioactive Compunds acting on Gaba (A) Receptors
This research is looking into the effect of biocompounds from two plants, Pokok Bidara (Zizyphus mauritiana) and Pokok Pala (Myristica fragans) in treating epilepsy disease. These biocompounds will be identified using high end chemistry equipment and will be tested into GAERS rat model to determine their effectiveness in absence seizures via the GABA (A) receptor.
The department’s research activities are fully supported by the Brain Research and Information Network (BRAINetwork) Cluster. Initiated in 2005 by the Vice-Chancellor of the university, it aims to promote an interdisciplinary approach to brain science research, integrating fundamental, developmental and clinical research. Apart from research, the department is committed to contribute to the growth of human resources in the country, initiating post-graduate studies in neurosurgery, neuroscience and neurology.