Mechanisms and therapeutic potential of microglia-regulated remyelination in chronic cerebral hypoperfusion.

Authors

Zherui Yang, Xiaoli Qin, Yunsha Zhang, Zixi Yan, Junjie Su, Shuo Kong, Guangxu Xiao, Shixin Xu

Published in

Experimental neurology. Pages 115980. Aug 14, 2026. Epub Aug 14, 2026.

Abstract

White matter injury after chronic cerebral ischemia is characterized by demyelination and impaired remyelination, representing a major contributor to neurological deficits and cognitive impairment. With the accelerating global aging population, the burden of cerebral small vessel disease and vascular cognitive impairment is increasing, and chronic cerebral ischemia has emerged as an important pathological basis for white matter damage and cognitive decline (Markus & Joutel, 2025). However, effective repair strategies for chronic cerebral hypoperfusion (CCH)-related white matter injury remain limited, highlighting the need to elucidate key mechanisms and develop targeted interventions (Rajeev et al., 2023). Persistent hypoperfusion induces oligodendrocyte dysfunction and impairs myelin repair through mechanisms involving metabolic disturbance, oxidative stress, and blood-brain barrier disruption. Microglia exert dual regulatory roles in this process: pro-inflammatory activation aggravates injury, whereas reparative responses promote remyelination through myelin debris clearance, neurotrophic factor secretion, and microenvironment modulation. In addition, interactions between microglia and astrocytes, endothelial cells, and immune cells collectively establish a cellular network regulating white matter repair. This review summarizes the molecular and cellular mechanisms underlying white matter injury after chronic cerebral ischemia, with particular emphasis on the dynamic regulation of microglia and their interactions with other cell types. Potential therapeutic strategies targeting microglial polarization, excessive inflammation, phagocytic function, and reparative transformation are also discussed. This review highlights the potential of microglia as therapeutic targets for promoting white matter repair and provides insights into future mechanistic studies and precision interventions.

PMID:
42600765
Bibliographic data and abstract were imported from PubMed on 15 Aug 2026.

Read full publication at:
Please sign in to see all details.

Stats

1-terrible, 9-excellent. How would you rate this publication? Sign in in to submit your rating.

Post a comment

You need to be signed in to post comments. You can sign in here.

Comments

There are no comments yet.