Microglial Polarization in Cerebral Ischemia

Microglia are the principal immune sentinels of the central nervous system and respond rapidly to cerebral ischaemia by adopting discrete activation states broadly categorised as pro-inflammatory (M1) or anti-inflammatory (M2). Within minutes to hours of vessel occlusion, microglia transition to an M1 phenotype, releasing cytokines and reactive oxygen species that exacerbate neuronal death and compromise the blood–brain barrier. Over ensuing days, a shift towards the M2 state promotes debris clearance, angiogenesis and tissue remodelling through release of trophic factors and anti-inflammatory mediators. The balance and timing of these phenotypic transitions are orchestrated by extracellular cues—such as cytokine milieu, lipid signals and damage-associated molecular patterns—and by intracellular pathways including NF-κB, AMPK–mTOR and PI3K–Akt. Dysregulation of microglial plasticity may prolong neuroinflammation, impede repair and worsen functional outcomes. Consequently, strategies that modulate microglial polarization offer promising avenues for limiting acute injury and enhancing recovery after stroke, with global implications for reducing morbidity and improving rehabilitation.

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Microglial Polarization in Cerebral Ischemia publication trend

The graph below shows the total number of articles in microglial polarization in cerebral ischemia across all publications each year (not limited to Nature Index journals).

Technical terms

Microglial polarization: The process by which microglia adopt distinct functional states in response to brain injury, commonly classified as pro-inflammatory (M1) or anti-inflammatory (M2).

M1 phenotype: A microglial activation state characterised by secretion of inflammatory mediators such as TNF-α, IL-6 and IL-1β, contributing to neuronal damage.

M2 phenotype: A reparative activation state in which microglia release anti-inflammatory and trophic factors to support debris clearance and tissue remodelling.

Exosomes: Nano-sized extracellular vesicles that transport lipids, proteins and genetic material between cells, modulating immune responses and repair.

Blood–brain barrier (BBB): The specialised endothelial interface that regulates molecular and cellular exchange between the circulatory system and the brain.

Lipid droplets: Intracellular organelles consisting of neutral lipids that influence cellular metabolism and may drive inflammatory phenotypes in microglia.

References

1. Dynamic Brain Lipid Profiles Modulate Microglial Lipid Droplet Accumulation and Inflammation Under Ischemic Conditions in Mice. Advanced Science (2024).
2. Panax notoginseng: derived exosome-like nanoparticles attenuate ischemia reperfusion injury via altering microglia polarization. Journal of Nanobiotechnology (2023).
3. SRGN amplifies microglia-mediated neuroinflammation and exacerbates ischemic brain injury. Journal of Neuroinflammation (2024).