Optogenetic calcium modulation in astrocytes enhances post-stroke recovery in chronic capsular infarct.

Abstract

Stroke is caused by disruption of cerebral blood flow, leading to neuronal death and dysfunction in the interconnected areas, which results in a wide range of severe symptoms depending on the specific brain regions affected. While previous studies have primarily focused on direct modulation of neuronal activity for post-stroke treatment, accumulating evidence suggests that astrocytes may play a critical role in post-stroke progression and could serve as a potential therapeutic target for recovery. In this study, we investigate the effects of selective modulation of astrocytic calcium signals on chronic stroke using OptoSTIM1, an optogenetic tool that activates endogenous calcium channels. In contrast to channelrhodopsin-2 (ChR2), OptoSTIM1 robustly elevates astrocytic calcium levels, sustaining the increase for over 10 min upon a single activation. The calcium elevation in astrocytes in the ipsilesional sensory-parietal cortex leads to remarkable recovery from post-stroke impairment. Thus, manipulating intracellular calcium levels in astrocytes holds promise as a potential therapeutic strategy for improving recovery following a stroke.