NMDA-INDUCED INCREASES IN RAT-BRAIN GLUTAMINE-SYNTHETASE BUT NOT GLIAL FIBRILLARY ACIDIC PROTEIN ARE MEDIATED BY FREE-RADICALS

Both excitotoxicity and oxidative stress are implicated in the pathoph ysiology of central nervous system (CNS) ischaemia-reperfusion injury whereby astrocytes offer neural protection through the production of e ndogenous antioxidants and removal of glutamate from the extracellular milieu. This study investigated whether exogenous alpha-tocopherol, a n antioxidant, could prevent N-methyl-D-aspartate (NMDA)-produced incr eases of the glial specific proteins, glutamine synthetase (GS) and gl ial fibrillary acidic protein (GFAP) in rat brain spheroids in vitro. NMDA (320 mu M; 3 days in vitro (DIV)) was unable to induce lipid pero xidation in rat brain spheroids implying that excitotoxicity in this s ystem did not involve substantial free radical formation. However at n oncytotoxic concentrations, increases in astroglial GS were prevented by alpha-tocopherol treatment, suggesting a role for ROS in the excito toxic process. In contrast, NMDA-induced increases in GFAP remained un changed by alpha-tocopherol indicating that oxidative stress may not b e involved in reactive gliosis at non-cytotoxic NMDA concentrations. ( C) 1998 Elsevier Science Ireland Ltd.