Scholarlink

<p>To evaluate the molecular and cellular mechanisms underlying cerebral small vessel disease (CSVD) pathophysiology, the blood-brain barrier (BBB) dysfunction, and emerging therapeutic strategies for cognitive impairment.&#xa0;We conducted a comprehensive review of recent literature examining the relationship between CSVD and BBB disruption, focusing on pathophysiological mechanisms and therapeutic approaches. Key databases were searched for relevant studies investigating inflammatory responses, lipid metabolism, endothelial dysfunction, and their impact on cognitive function in CSVD. BBB disruption plays a central role in CSVD pathogenesis, characterized by increased permeability that triggers neuroinflammatory cascades and subsequent cognitive deterioration. Neuroinflammation, oxidative stress, and disrupted lipid metabolism synergistically contribute to BBB breakdown, creating a detrimental feedback loop. Therapeutic strategies targeting these pathways, including vascular risk factor management, anti-inflammatory interventions, and non-pharmacological approaches such as cognitive training and physical exercise, show promising results in preserving cognitive function in CSVD patients. This review provides critical insights into the complex interplay between CSVD and BBB integrity, emphasizing BBB disruption as both a consequence and amplifier of CSVD-related pathology. Understanding these mechanisms offers novel perspectives for developing targeted interventions to mitigate cognitive decline in affected individuals and addresses a significant public health challenge in our aging global population. We also integrate recent evidence connecting BBB leakage to lipid dysmetabolism, EndMT, and impaired perivascular clearance, and propose a BBB-centered framework for CSVD-related cognitive impairment.</p> Graphical Abstract <p>Overview of BBB-centered mechanisms and therapeutic strategies in CSVD-related cognitive impairment. Inflammatory responses, endothelial dysfunction, and lipid metabolism dysregulation contribute to BBB dysfunction, which is linked to CSVD and cognitive impairment. Potential strategies include non-pharmacological interventions, vascular risk factor control, anti-inflammatory and antioxidant approaches, and neuroprotection. <b>Abbreviations</b>: CSVD, cerebral small vessel disease; BBB, blood–brain barrier; ECs, endothelial cells.</p> <p></p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Cerebral Small Vessel Disease and Blood-Brain Barrier Disruption: Mechanisms and Therapeutic Strategies in Cognitive Impairment

  • 期刊论文

  • 发表日期：

    2026年3月26日

查看全文
  • Yang Yang,
  • Yuhang Qian,
  • Jun Huang,
  • Ying Luo

摘要

To evaluate the molecular and cellular mechanisms underlying cerebral small vessel disease (CSVD) pathophysiology, the blood-brain barrier (BBB) dysfunction, and emerging therapeutic strategies for cognitive impairment. We conducted a comprehensive review of recent literature examining the relationship between CSVD and BBB disruption, focusing on pathophysiological mechanisms and therapeutic approaches. Key databases were searched for relevant studies investigating inflammatory responses, lipid metabolism, endothelial dysfunction, and their impact on cognitive function in CSVD. BBB disruption plays a central role in CSVD pathogenesis, characterized by increased permeability that triggers neuroinflammatory cascades and subsequent cognitive deterioration. Neuroinflammation, oxidative stress, and disrupted lipid metabolism synergistically contribute to BBB breakdown, creating a detrimental feedback loop. Therapeutic strategies targeting these pathways, including vascular risk factor management, anti-inflammatory interventions, and non-pharmacological approaches such as cognitive training and physical exercise, show promising results in preserving cognitive function in CSVD patients. This review provides critical insights into the complex interplay between CSVD and BBB integrity, emphasizing BBB disruption as both a consequence and amplifier of CSVD-related pathology. Understanding these mechanisms offers novel perspectives for developing targeted interventions to mitigate cognitive decline in affected individuals and addresses a significant public health challenge in our aging global population. We also integrate recent evidence connecting BBB leakage to lipid dysmetabolism, EndMT, and impaired perivascular clearance, and propose a BBB-centered framework for CSVD-related cognitive impairment.

Graphical Abstract

Overview of BBB-centered mechanisms and therapeutic strategies in CSVD-related cognitive impairment. Inflammatory responses, endothelial dysfunction, and lipid metabolism dysregulation contribute to BBB dysfunction, which is linked to CSVD and cognitive impairment. Potential strategies include non-pharmacological interventions, vascular risk factor control, anti-inflammatory and antioxidant approaches, and neuroprotection. Abbreviations: CSVD, cerebral small vessel disease; BBB, blood–brain barrier; ECs, endothelial cells.