Rapid loss of glutamine synthetase from astrocytes in response to hypoxia: implications for excitotoxicity

We have examined brains of neonatal pigs that were rendered hypoxic. Glutamine synthetase (GS), a key enzyme in the detoxification of glutamate and ammonia, was rapidly lost from astrocytes in regions susceptible to damage, including the CA1 of hippocampus and various cortical regions. Conversely, resilient areas such as the dentate gyrus exhibited little or no loss of GS. Onset of loss was rapid, patches of loss being evident by 1h post-insult, and loss was extensive by 24h and did not recover by 72 h. Examination of counterstained sections revealed that GS losses preceded any overt neuronal damage. Loss of GS from astrocytes would plausibly lead to a rise in intracellular glutamate, and could explain why reversal of astrocytic glutamate transport during hypoxia/ischaemia is conceptually possible.