Transient lack of glucose but not O2 is involved in ischemic postconditioning-induced neuroprotection

Cerebral ischemic postconditioning has emerged recently as a kind of endogenous strategy for neuroprotection. We set out to test whether hypoxia or glucose deprivation (GD) would substitute for ischemia in postconditioning.

Adult male C57BL/6J mice were treated with postconditioning evoked by ischemia (bilateral common carotid arteries occlusion) or hypoxia (8% O(2) ) after 45-min middle cerebral arterial occlusion. Corticostriatal slices from mice were subjected to 1-min oxygen-glucose deprivation (OGD), GD, or oxygen deprivation (OD) postconditioning at 5 min after 15-min OGD.

Hypoxic postconditioning did not decrease infarct volume or improve neurologic function at 24 h after reperfusion, while ischemic postconditioning did. Similarly, OGD and GD but not OD postconditioning attenuated the OGD/reperfusion-induced injury in corticostriatal slices. The effective duration of low-glucose (1 mmol/L) postconditioning was longer than that of OGD postconditioning. Moreover, OGD and GD but not OD postconditioning reversed the changes of glutamate, GABA, glutamate transporter-1 protein expression, and glutamine synthetase activity induced by OGD/reperfusion.

These results suggest that the transient lack of glucose but not oxygen plays a key role in ischemic postconditioning-induced neuroprotection, at least partly by regulating glutamate metabolism. Low-glucose postconditioning might be a clinically safe and feasible therapeutic approach against cerebral ischemia/reperfusion injury.