Neuroinflammation in Ischemic Stroke: Focusing on the Critical Role of Microglia

Abstract

Background:
Ischemic stroke is a leading cause of death and long-term disability worldwide. Neuroinflammation is a central component in its pathogenesis, and microglia play a pivotal role in mediating inflammatory responses and influencing neuronal survival.

Objective:
This review aims to summarize current findings on the role of microglia in ischemic stroke and their interaction with various programmed cell death pathways, as well as to explore the impact of the gut–brain axis in post-stroke outcomes.

Methods:
A comprehensive review of recent literature was conducted, focusing on studies addressing microglial activation, neuroinflammatory signaling pathways, and mechanisms of cell death, including necroptosis, autophagy, pyroptosis, ferroptosis, and efferocytosis. The influence of the gut microbiota on microglial behavior and stroke outcomes was also examined.

Results:
Microglia exhibit dual roles, either aggravating neuroinflammation through pro-inflammatory phenotypes or promoting recovery via anti-inflammatory actions. Their crosstalk with various cell death pathways influences the extent of neuronal injury and tissue recovery. The gut microbiota exerts a modulatory effect on neuroinflammation via the gut–brain axis, offering potential targets for therapeutic intervention. Advances in omics and animal models provide deeper insights into these mechanisms.

Conclusion:
Microglia are crucial regulators of neuroinflammation and interact with multiple cell death pathways in ischemic stroke. Targeting microglial polarization and their communication with the gut microbiota may offer promising avenues for future therapies. Understanding these processes through integrated molecular approaches could enhance neuroprotective strategies and improve post-stroke recovery outcomes.