Blood-Brain Barrier Dysfunction and the Potential Mechanisms in Chronic Cerebral Hypoperfusion Induced Cognitive
WenQing Xu1, Qingke Bai2, Qiang Dong3
1Department of Neurology, Huashan Hospital, Fudan University, Shanghai, China.
Insights
Chronic cerebral hypoperfusion (CCH) causes vascular cognitive impairment and dementia (VCID) by disrupting the blood-brain barrier (BBB). Targeting BBB dysfunction offers potential therapeutic benefits for cognitive decline.
Area of Science:
- Neuroscience
- Cerebrovascular Medicine
- Pathology
Background:
- Chronic cerebral hypoperfusion (CCH) is a significant contributor to vascular cognitive impairment and dementia (VCID).
- Blood-brain barrier (BBB) dysfunction is increasingly recognized as a key pathological feature in CCH.
- Early BBB breakdown in CCH correlates with white matter deterioration and cognitive deficits.
Purpose of the Study:
- To review current experimental and clinical evidence linking BBB disruption to VCID.
- To elucidate the mechanisms underlying BBB dysfunction in CCH.
- To explore the potential role of APOE genotype in BBB pathology and therapeutic strategies.
Main Methods:
- Literature review of experimental and clinical studies on CCH and VCID.
- Analysis of mechanisms involving cell interactions at the BBB.
- Discussion of the influence of genetic factors, such as APOE genotype.
Main Results:
- BBB dysfunction is a critical early event in CCH, preceding or coinciding with cognitive impairment.
- Mechanisms involve complex cellular interactions within the BBB and are influenced by factors like APOE genotype.
- Evidence supports BBB disruption as a major driver of VCID.
Conclusions:
- BBB dysfunction is a pivotal pathological mechanism in CCH-induced VCID.
- Understanding these mechanisms offers insights into potential therapeutic targets.
- Interventions aimed at restoring BBB integrity may hold promise for treating cognitive impairment in CCH.
Abstract:
Chronic cerebral hypoperfusion (CCH) is a major cause of vascular cognitive impairment and dementia (VCID). Although the underlying mechanisms have not been fully elucidated, the emerging data suggest that blood-brain barrier (BBB) dysfunction is one of the pivotal pathological changes in CCH. BBB dysfunction appears early in CCH, contributing to the deterioration of white matter and the development of cognitive impairment. In this review, we summarize the latest experimental and clinical evidence implicating BBB disruption as a major cause of VCID. We discuss the mechanisms of BBB dysfunction in CCH, focusing on the cell interactions within the BBB, as well as the potential role of APOE genotype. In summary, we provide novel insights into the pathophysiological mechanisms underlying BBB dysfunction and the potential clinical benefits of therapeutic interventions targeting BBB in CCH.
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