Electrophysiological Signatures in Global Cerebral Ischemia: Neuroprotection Via Chemogenetic Inhibition of CA1 Pyramidal Neurons in Rats

Abstract

Background Although there has been limited research into the perturbation of electrophysiological activity in the brain after ischemia, the activity signatures during ischemia and reperfusion remain to be fully elucidated. We aim to comprehensively describe these electrophysiological signatures and interrogate their correlation with ischemic damage during global cerebral ischemia and reperfusion. Methods and Results We used the 4‐vessel occlusion method of inducing global cerebral ischemia in rats. We used in vivo electrophysiological techniques to simultaneously record single units, scalp electroencephalogram, and local field potentials in awake animals. Neuronal damage and astrocyte reactivation were examined by immunofluorescence, immunoblotting, and quantitative real‐time reverse‐transcription polymerase chain reaction under chemogenetic inhibition of glutamatergic neurons. Electroencephalogram/local field potentials power and phase‐amplitude coupling of the theta and low‐gamma bands were reduced during ischemia and the acute phase of reperfusion. The firing rate of single units was enhanced by ischemia–reperfusion, and the phase relationship between the local field potentials theta band and neuronal firing was altered. Precise inhibition of hippocampus CA1 pyramidal neuron hyperactivity by chemogenetics rescued the firing dysfunction, ischemic neuronal damage, and A1 astrocyte activation. Conclusions Our results provide a comprehensive description of the characteristics of electrophysiological activity that accompany ischemia–reperfusion and highlight the significance of this activity in ischemic damage.

Keywords

• astrocyte activation
• chemogenetic modulation
• global cerebral ischemia
• in vivo electrophysiology
• ischemic damage