Preliminary evidence suggests adenosine, a neuromodulator, has neuroprotective properties during cerebral ischemia. It is unclear, however, if adenosine has glioprotective effects. We studied the effect of adenosine on cellular injury in astroglial cultures subjected to combined glucose-oxygen deprivation. Adenosine (100-1,000~tM)dramatically reduced astroglial injury, whereas the adenosine agonists 2-chloroadenosine (10 nM-100 bIM), N 6-cyclopentyladenosine (1 nM-10~.tM),5'-Nethylcarboxamidoadenosine (10 nM-100 1.tM), and N

Abbreviations used: 1 S,3R-ACPD, (I S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid ; AMPA, a-amino-3-hydroxy-5-methyl-4isoxazole-4-propionic acid ; AP3, L(+)-2-amino-3-phosphonopropionic acid ; CGOD, combined glucose-oxygen deprivation ; DAG, diacylglycerol ; IP, myo-inositol phosphate ; IP,, myo-inositol monophosphate ; IPZ , myo-inositol bisphosphate ; IP,, myo-inositol trisphosphate ; LDH, lactate dehydrogenase : MCPG, ( )-a-methyl-4carboxyphenylglycine ; mG1uR, metabotropic glutamate receptor ; NMDA, N-methyl-D-aspartate ; PIP2 , phosphatidylinositol bisphosphate .

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Membrane phospholipid degradation has been proposed to play a key role in hypoxic-ischemic brain injury. We tested the hypotheses that both nordihydroguaiaretic acid, a phospholipase A2 and lipoxygenase inhibitor, and RHC 80267, a diacylglycerol lipase inhibitor, would decrease the release of [3H]arachidonic acid metabolites from prelabeled cultures of astroglia subjected to combined glucose-oxygen deprivation and that these inhibitors would also decrease astroglial injury during combined glucose-oxygen deprivation. Both nordihydroguaiaretic acid and RHC 80267 significantly inhibited the release of [3H]arachidonic acid metabolites during combined glucose-oxygen deprivation. This suggests that two separate enzymic pathways, the phospholipase A2 pathway and the phospholipase C/diacylglycerol lipase pathway, contribute to the release of astroglial [3H]arachidonic acid metabolites during combined glucose-oxygen deprivation. However, both of these lipase inhibitors increased astroglial cell death during combined glucose-oxygen deprivation, probably due to inhibition of arachidonic acid release. We speculate that arachidonic acid release may be a mechanism of astroglial self-preservation during combined glucose-oxygen deprivation.

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