Head Mild Hypothermia Exerts a Neuroprotective Role in Ischemia–Reperfusion Injury by Maintaining Glial Glutamate Transporter 1

Stroke is the second leading cause of death worldwide; nevertheless, its pathological mechanism still remains unclear. Besides, there is an urgent need to find new effective treatment strategies for patients with stroke. Hypothermia therapy is widely used in clinical as a neuroprotective strategy practice. However, the exact mechanism is not fully understood. In this study, we examined the effects of hypothermia on glial glutamate transport-1 (GLT-1) and the extracellular glutamate concentration ([Glu]e) in cerebral ischemia-reperfusion insult rats. Our results revealed that cerebral brain ischemia-reperfusion caused the decrease of GLT-1 and Bcl-2, the increase of Bax and [Glu]e, and caused neuron loss. On the contrary, head mild hypothermia (HMH) for 2 hours alleviated the abovementioned effects and exerted neuroprotection. In the hypothermia group, pretreatment with dihydrokainate, a functional antagonist of GLT-1 by lateral ventricle injection partly reversed the abovementioned effect of HMH. Our results suggest that HMH could exert a neuroprotective role by maintaining GLT-1 and reducing the excitotoxicity of [Glu]e during ischemia-reperfusion insult in rats.