Abstract 24: Transient Lack of Glucose but Not Oxygen is Involved in Ischemic Postconditioning-Induced Neuroprotection in Mouse Corticostriatal Slices by Regulating Glutamate Metabolism
Objective: Cerebral ischemic postconditioning has emerged recently as a kind of endogenous strategy for neuroprotection. However, its protective mechanisms are largely unknown. We hypothesized that glucose deprivation (GD) and oxygen deprivation (OD) play different roles in ischemic postconditioning-induced neuroprotection.
Methods: Corticostriatal slices from adult male C57BL/6J mice were subjected to a 15-min oxygen-glucose deprivation (OGD), and 5 min later, treated with or without 1 min of OGD, GD or OD postconditioning. Brain slices were harvested 1 h after reperfusion for measuring 2,3,5-triphenyltetrazolium chloride conversion to quantify cell injury, determining glutamate and GABA levels, glutamate transporter GLT-1 expression or glutamine synthetase (GS) activity. Mice were also subjected to middle cerebral arterial occlusion for 45 min and then treated with or without hypoxic postconditioning (8% O2) with different modes applied in the early period of reperfusion. The infarct size and neurological function were evaluated at 24 h after reperfusion.
Results: OGD postconditioning significantly attenuated OGD/reperfusion-induced injury. GD postconditioning also produced significant protection which was comparable with the effect of OGD postconditioning, while the benefit effect was not observed when OD postconditioning was applied. Postconditioning evoked by OGD and GD but not OD abolished the increase of excitatory neurotransmitter glutamate and the decrease of inhibitory neurotransmitter GABA induced by OGD/reperfusion. They also reversed OGD/reperfusion-induced down-regulation of GLT-1 expression and GS activity in astrocytes, which maintain glutamate metabolism balance. In addition, application of hypoxic postconditioning in the early period of reperfusion did not improve neurological function or decrease infarct size after brain ischemia, which is consistent with the results in brain slices.
Conclusions: These results suggest that GD in ischemic postconditioning is the main factor inducing neuroprotection. This effect may be associated with retaining GLT-1 expression and GS activity in astrocytes, which may further regulate glutamate and GABA levels and inhibit ischemia/reperfusion-induced injury.
- © 2010 by American Heart Association, Inc.