Transient ischemia-reperfusion induces cortical hyperactivity and AMPAR trafficking in the somatosensory cortex.

Yuanyuan Li,Shaowei Hou,Hui Shen,Shiyang Yuan,Feifei Wang,Feng Chen,Robert H Cudmore,Yan Zhang,Cuiping Guo,Zengguang Ma,Liangpeng Wei,Aili Liu,Xiaochuan Wang,Ran Ding

doi:10.18632/aging.102881

Abstract

Brain ischemia results from cardiac arrest, stroke or head trauma. The structural basis of rescuing the synaptic impairment and cortical dysfunctions induced in the stage of ischemic-reperfusion can occur if therapeutic interventions are applied in time, but the functional basis for this resilience remains elusive. Here, we explore the changes in cortical activity and a-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor (AMPAR) GluA1 subunit in spine (sGluA1) after transient ischemia-reperfusion in vivo for 28 days. Using in vivo two-photon microscopy in the mouse somatosensory cortex, we found that the average frequency of Ca2+ transients in the spine (there was an unusual synchrony) was higher after 15 min of ischemia-reperfusion. In addition, the transient ischemia-reperfusion caused a reflective enhancement of AMPARs, which eventually restored to normal. The cortical hyperactivity (Ca2+ transients) and the increase in AMPARs were successfully blocked by an NMDA receptor antagonist. Thus, the increase of AMPARs, cortical hyperactivity and the unusual synchrony might be the reason for reperfusion injury after short-term transient ischemia.

Highlights

Compared to other tissues and organs in the body, the brain is vulnerable to ischemic injury
We examined the effects of transient global ischemia on spine activity levels by ligating the bilateral common carotid arteries (BCAL) (Figure 1H)
Our study investigated the changes in cortical activity and found significant increases in spine and neuronal activity levels

Summary

Introduction

Compared to other tissues and organs in the body, the brain is vulnerable to ischemic injury. There are many reports on the neurotoxic properties of glutamate connected with the activation of AMPAR, which leads to changes in the permeability of the postsynaptic membrane for monovalent ions (sodium and potassium), the enhancement of sodium influx, and short-term depolarization of the postsynaptic membrane [12]. This in turn leads to enhancement of calcium influx into cells via both agonist-dependent and potential-dependent channels [3, 13, 14]. The restored dendritic structures remain plastic to rebuild the cortical network [2] and activity-dependent changes in AMPAR [15] after ischemia-reperfusion have been examined, the trafficking of AMPAR in vivo during ischemia-reperfusion in real time has not been previously studied

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Results

Conclusion