Roles of Microglia in Cerebral Small Vessel Disease

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.