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Roles of Microglia in Cerebral Small Vessel Disease
Chenyang Jin1,2, Xiaoqian Song1, Yuewen Sun1
1Department of Geriatric Medicine, Affiliated Hospital of Qingdao University, Qingdao, China.
Backgrounds:
Cerebral small vessel disease (CSVD) is a major cause of vascular dementia, characterized by heterogeneous pathologies affecting the brain's microvasculature. In recent years, researchers have recognized the significant role of neuroinflammation and increased permeability of the blood-brain barrier (BBB) in the development of CSVD. Within this framework, microglia exert multifaceted roles.
Methods:
This review synthesizes current evidence on microglial involvement in CSVD, covering their heterogeneity, associations with neuroimaging markers, pathogenic mechanisms, and the translational prospects of microglia-directed therapies.
Results:
Chronic cerebral hypoperfusion drives microglial activation toward pro-inflammatory phenotypes, triggering oxidative stress, inflammatory mediator release, and BBB disruption. These pathological changes correlate spatially with white matter hyperintensities, enlarged perivascular spaces, and lacunes. Microglia also interact with other glial cells to modulate disease progression. Preclinical studies have shown that modulating microglial phenotypes can be beneficial, though clinical translation remains challenging.
Conclusion:
Microglia serve as pivotal double-edged players, central to both neuroinflammation and BBB dysfunction in CSVD.Understanding the intricate relationship between microglia and CSVD is essential for elucidating the underlying mechanisms and paves the way for novel therapeutic approaches.
Insights
Microglia play a dual role in cerebral small vessel disease (CSVD), contributing to neuroinflammation and blood-brain barrier (BBB) dysfunction. Targeting these cells offers potential therapeutic avenues for vascular dementia.
Area of Science:
- Neuroscience
- Pathology
- Vascular Biology
Background:
- Cerebral small vessel disease (CSVD) is a primary cause of vascular dementia, involving diverse pathologies in brain microvasculature.
- Neuroinflammation and blood-brain barrier (BBB) permeability are increasingly recognized as key factors in CSVD pathogenesis.
- Microglia exhibit complex and varied roles within the CSVD framework.
Purpose of the Study:
- To review current research on microglial involvement in CSVD.
- To explore microglial heterogeneity, neuroimaging correlations, and pathogenic mechanisms.
- To discuss the potential of microglia-targeted therapies for CSVD.
Main Methods:
- Literature review synthesizing evidence on microglia in CSVD.
- Analysis of microglial phenotypes, BBB integrity, and neuroimaging markers.
- Examination of preclinical findings and challenges in clinical translation.
Main Results:
- Chronic hypoperfusion activates microglia towards pro-inflammatory states, inducing oxidative stress and BBB damage.
- CSVD pathologies like white matter hyperintensities correlate with these microglial-driven changes.
- Microglia interact with other glial cells, influencing disease progression; preclinical models show therapeutic promise.
Conclusions:
- Microglia are central to CSVD, acting as key mediators of neuroinflammation and BBB dysfunction.
- Understanding the microglia-CSVD relationship is crucial for uncovering disease mechanisms.
- Targeting microglial pathways presents a promising strategy for novel CSVD therapeutics.
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