Abstract
Key pathological features of cerebral small vessel disease (cSVD) include impairment of the blood brain barrier (BBB) and the progression of white matter lesions (WMLs) amongst other structural lesions, leading to the clinical manifestations of cSVD. The function of endothelial cells (ECs) is of major importance to maintain a proper BBB. ECs interact with several cell types to provide structural and functional support to the brain. Oligodendrocytes (OLs) myelinate axons in the central nervous system and are crucial in sustaining the integrity of white matter. The interplay between ECs and OLs and their precursor cells (OPCs) has received limited attention yet seems of relevance for the study of BBB dysfunction and white matter injury in cSVD. Emerging evidence shows a crosstalk between ECs and OPCs/OLs, mediated by signaling through the Wingless and Int-1 (WNT)/β-catenin pathway. As the latter is involved in EC function (e.g., angiogenesis) and oligodendrogenesis, we reviewed the role of WNT/β-catenin signaling for both cell types and performed a systematic search to identify studies describing a WNT-mediated interplay between ECs and OPCs/OLs. Dysregulation of this interaction may limit remyelination of WMLs and render the BBB leaky, thereby initiating a vicious neuroinflammatory cycle. A better understanding of the role of this signaling pathway in EC–OL crosstalk is essential in understanding cSVD development.
Highlights
Cerebral small vessel disease is an umbrella term used to describe different pathological processes that affect the small vessels of the brain, including small arteries, arterioles, capillaries, and small veins, and is associated with brain structural lesions and eventual cognitive impairment [1].With cSVD accounting for up to 25% of all stroke and 45% of dementia, it is seen as a common cause of cognitive impairment worldwide [2]
This review aimed to summarize the published findings on the crosstalk between Endothelial cells (ECs) and OLs and their precursor cells (OPCs)/OLs, and in particular the role played by Wingless and Int-1 (WNT)/β-catenin signaling in this interaction
We suggest that the activation of WNT7a and WNT7b signaling in healthy ECs and OPCs/OLs in response to injury may help the recruitment of new OPCs at sites of demyelination via the structural support of cerebral vessels
Summary
Cerebral small vessel disease (cSVD) is an umbrella term used to describe different pathological processes that affect the small vessels of the brain, including small arteries, arterioles, capillaries, and small veins, and is associated with brain structural lesions and eventual cognitive impairment [1]. With cSVD accounting for up to 25% of all stroke and 45% of dementia, it is seen as a common cause of cognitive impairment worldwide [2]. Mood and gait disorders are often seen in cSVD patients [3]. Damage to the blood brain barrier (BBB) is recognized as an early pathological step in cSVD, often resulting from the exposure to cardiovascular risk factors, such as hypertension and diabetes [2,4,5]. Endothelial cells (ECs) are essential for BBB function due to their tight junction (TJ)
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