Smooth muscle cells of intracranial vessels: from development to disease

Cerebrovascular diseases that cause ischaemic or haemorrhagic stroke with subsequent loss of life or functional capacity due to damage of the brain tissue are among the leading causes of human suffering and economic burden inflicted by diseases in the developed world. Diseases affecting intracranial vessels are significant contributors to ischaemic and haemorrhagic strokes. Brain arteriovenous malformations, which are a collection of abnormal blood vessels connecting arteries to veins, are the most common cause of intracranial haemorrhage in children and young adults. Saccular intracranial aneurysms, which are pathological saccular dilations mainly occurring at bifurcations of the large intracranial arteries near the circle of Willis, are highly prevalent in the middle-aged population, causing significant anxiety and concern; their rupture, although rare, is a significant cause of intracranial haemorrhage in those past middle age that is associated with a very sinister prognosis. Cerebral small-vessel disease, which comprise all pathological processes affecting vessels <500 microns in diameter, account for the majority of intracerebral haemorrhages and ∼25% of ischaemic strokes and 45% of dementias in the elderly. In this review, we summarize the developmental, structural, and functional features of intracranial vessels. We then describe the role of smooth muscle cells in brain arteriovenous malformations, intracranial aneurysms, and small-vessel diseases, and discuss how the peculiar ontogeny, structure, and function of intracranial vessels are related to the development of these diseases.