Increased GluA1 Expression, c-Fos Activation, and MAP2 Loss During Early Cerebral Ischemia-reperfusion

The disruption of excitatory and inhibitory neurotransmission is a key pathological event in ischemia/reperfusion injury. However, the temporal relationship among glutamatergic activation, inhibitory responses, and neuronal activity in the early phase of reperfusion remains unclear. The present study investigated changes in GluA1 signaling, GABA_A receptor α1 expression, neuronal activation, and neuronal integrity following transient cerebral ischemia.

Transient focal cerebral ischemia was induced in male C57BL/6 mice by middle cerebral artery occlusion (MCAO). Mice were sacrificed immediately following ischemia (0 h) or 3 h after reperfusion. The expression levels of phosphorylated GluA1 (pGluA1), total GluA1, and GABA_A receptor α1 in the ipsilateral cortex were analyzed by western blotting. Neuronal activation and integrity were evaluated using immunofluorescence staining for c-Fos and MAP2, respectively.

The expression levels of pGluA1 and total GluA1 increased following MCAO and remained elevated after 3 h of reperfusion, whereas the pGluA1/total GluA1 ratio did not differ significantly among the experimental groups. GABA_A receptor α1 expression did not differ significantly among the groups, although it tended to be higher after reperfusion. Immunofluorescence revealed a focal reduction in MAP2 immunoreactivity in the reperfusion group, while no obvious changes were observed immediately after ischemia. In addition, c-Fos immunoreactivity increased in both the ischemic and reperfusion groups compared with the sham group.

Early cerebral ischemia-reperfusion is characterized by progressive activation of GluA1 signaling, increased neuronal activity, and the onset of neuronal injury. GABA_A receptor α1 expression showed a non-significant tendency to be higher after reperfusion, and the functional significance of this trend remains uncertain. These findings indicate that early cerebral ischemia-reperfusion is associated with altered GluA1 expression, increased neuronal activity, and early neuronal injury.