Pre-treatment or post-treatment with hydroxychloroquine demonstrates neuroprotective effects in cerebral ischemia/reperfusion

Abstract

Stroke is a serious life-threatening medical condition and is one of the principal reasons for death and disabilities worldwide. The aim of the present study was to determine the neuroprotective effects of hydroxychloroquine (HCQ) and the timing of its administration in cerebral ischemia/reperfusion (I/R) in rats. A global I/R model was used, and HCQ was administered in either pre- or post-treatment doses of 25 and 50 mg/kg. Effects of HCQ on infarct size, histological changes, oxidative stress, and learning and memory were evaluated. Phospho-AMPK and SQSTM1/p62 protein levels were also measured to elucidate the possible mechanisms involved. HCQ in both pre- (at doses of 25 and 50 mg/kg) or post-treatment (at a dose of 50 mg/kg) protocols reduces brain infarct size and histopathological changes and improves learning and memory after cerebral I/R. Pre-treatment with HCQ reduced AMPK activity with no significant effect on SQSTM1/p62 increment. Post-treatment with HCQ increased AMPK activity and SQSTM1/p62 protein levels. Our results show the neuroprotective effects of HCQ on cerebral I/R through the reduction in infarct size, histopathological changes, and improvement in memory and learning functions. Moreover, AMPK and autophagy may play a role in this protective effect.

Keywords: AMPK; autophagy; cerebral ischemia/reperfusion; hydroxychloroquine; infarct size.