Journal of Clinical and Cellular Immunology
Open Access
ISSN: 2155-9899
ISSN: 2155-9899
Mojtaba Farjam
Accepted Abstracts: J Clin Cell Immunol
Neurodegeneration is the pathophysiological basis for permanent neurological disabilities in multiple sclerosis (MS); thus neuroprotection is emerging as a therapeutic approach in MS research. Modulation of excitotoxicity by inhibition of NMDARs has been suggested for neuroprotection. Decrease in Calcium-dependent protease activity secondary to NMDAR inhibition, has been postulated as a mechanism for this approach. However, this probable mechanism remains to be proven yet. Moreover, selective antagonisation of NR2B subtype of these receptors, an NMDAR subtype believed to play a more pivotal role in neurodegeneration, has not been studied too. In this study, the effect of inhibition of NR2B-containing NMDAR was evaluated on the animal model of MS, experimental autoimmune encephalomyelitis (EAE). EAE induction was done using MOG in C57/Bl6 mice. Therapeutic administration of different doses of highly selective NR2B-containing NMDAR inhibitor (RO25-6981) was compared with memantine (non-selective NMDAR antagonist) and vehicle in different experimental groups. Behavioral, histological and western blot analysis of Calpain and Caspase 3-dependent α-spectrin break down were studied comparatively among groups. Neurological deficits in EAE animals were more efficiently decreased by selective inhibition of NR2B-containing NMDARs. Histological studies of the spinal cords also showed decreased inflammation, myelin degradation, neuro-axonal degeneration and Calpain activity when RO25-6981was administered with higher doses. Regarding the role of NR2B-containing NMDARs in excitotoxicity, selective inhibition of these receptor subtypes appears to modulate the neurological disabilities and pathological changes in EAE. Decreasing the activity of Calcium-dependent protease, Calpain, by blockade of NR2B-containing NMDAR using high dose of RO25-6981 can be seen simultaneously. More experimental studies could be performed to suggest NR2B-containing NMDAR inhibition as a potentially effective treatment strategy for slowing down the clinical deterioration of disability in MS .
Mojtaba Farjam graduated in Medicine in 2001 and received a PhD degree in Medical Pharmacology from Shiraz University of Medical Sciences, Iran in 2012. He studied neuroimmune pharmacology of multiple sclerosis as a Research Scholar in Thomas Jefferson Medical College PA, USA in 2012. Currently, he is the Scientific Executive of Fasa Cohort Study Center, Fasa, Iran and Assistant Professor of Medical Pharmacology in Fasa University of Medical Sciences. He has been working in Fars MS Aid Charity as advisor and supervisor of the data base in this organization since 2010.