PI3K/AKT pathway: A potential therapeutic target in cerebral ischemia-reperfusion injury

Abstract

Cerebral ischemia is a prevalent cerebrovascular disorder, with the restoration of blocked blood vessels serving as the current standard clinical treatment. However, reperfusion can exacerbate neuronal damage and neurological dysfunction, resulting in cerebral ischemia-reperfusion (I/R) injury. Presently, clinical treatment strategies for cerebral I/R injury are limited, creating an urgent need to identify new effective therapeutic targets. The PI3K/AKT signaling pathway, a pro-survival pathway associated with cerebral I/R injury, has garnered significant attention. We conducted a comprehensive review of the literature on the PI3K/AKT pathway in the context of cerebral I/R. Our findings indicate that activation of the PI3K/AKT signaling pathway following cerebral I/R can alleviate oxidative stress, reduce endoplasmic reticulum stress (ERS), inhibit inflammatory responses, decrease neuronal apoptosis, autophagy, and pyroptosis, mitigate blood-brain barrier (BBB) damage, and promote neurological function recovery. Consequently, this pathway ultimately reduces neuronal death, alleviates brain tissue damage, decreases the volume of cerebral infarction, and improves behavioral impairments. These results suggest that the PI3K/AKT signaling pathway is a promising therapeutic target for further research and drug development, holding significant potential for the treatment of cerebral I/R injury.