Please use this identifier to cite or link to this item: http://scholarbank.nus.edu.sg/handle/10635/37595
Title: ROLE OF GLIAL N-METHYL D-ASPARTATE RECEPTORS IN PATHOGENISIS OF HYPOXIC PERIVENTRICULAR WHITE MATTER DAMAGE
Authors: MADHUVIKA MURUGAN
Keywords: hypoxia, white matter, NMDA receptors, microglia, astrocytes, oligodendrocytes
Issue Date: 23-Aug-2012
Source: MADHUVIKA MURUGAN (2012-08-23). ROLE OF GLIAL N-METHYL D-ASPARTATE RECEPTORS IN PATHOGENISIS OF HYPOXIC PERIVENTRICULAR WHITE MATTER DAMAGE. ScholarBank@NUS Repository.
Abstract: Perinatal hypoxia affects the periventricular white matter (PWM) causing damage to axons and oligodendrocytes, and is the substrate of several neurological impairments including cerebral palsy. Hypoxia-induced release of excess glutamate is considered to be a key mediator of PWM damage (PWMD). Hence, the aim of the present study was to identify the role of glutamate receptor-mediated excitotoxicity, with focus on glial N-methyl D-aspartate receptor (NMDAR) as a mediator of PWMD. It was shown that dysregulated functioning of astroglial glutamate transporters was primarily responsible for increased glutamate levels following hypoxic exposure. Excess glutamate in hypoxic PWM mediated excitotoxicity to oligodendrocytes by directly activating NMDAR in them and indirectly by activating the receptors on astrocytes and microglia. Under hypoxic conditions, activation of NMDAR in oligodendrocytes triggered its apoptosis. Also, NMDAR-mediated calcium influx in astroglia spread to the oligodendrocytes via gap junctions evoking an apoptotic response in the latter cell type. While microglial NMDAR augmented the production of nitric oxide and proinflammatory cytokines via the NF-kB signalling pathway, resulting in the death of oligodendrocytes and thereby contributing to PWMD. In the light of the above, glial NMDAR is believed to a potential therapeutic target for the treatment of neonatal hypoxic PWMD.
URI: http://scholarbank.nus.edu.sg/handle/10635/37595
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