Cerebral small vessels feed and protect the brain parenchyma thanks to the unique features of the blood-brain barrier. Cerebrovascular dysfunction is therefore seen as a detrimental factor for the initiation of several central nervous system (CNS) disorders, such as stroke, cerebral small vessel disease (cSVD), and Alzheimer's disease. The main working hypothesis linking cerebrovascular dysfunction to brain disorders includes the contribution of neuroinflammation. While our knowledge on microglia cells-the brainresident immune cells-has been increasing in the last decades, the specific populations of microglia and macrophages surrounding brain vessels, vessel-associated microglia (VAM), and perivascular macrophages (PVMs), respectively, have been overlooked. This review aims to summarize the knowledge gathered on VAM and PVMs, to discuss existing knowledge gaps of importance for later studies and to summarize evidences for their contribution to cerebrovascular dysfunction.
The combination therapy with sitagliptin and low dosage sulphonylureas was safe and effective for glycaemic control. Glucagon loading test indicated that 1 year administration of sitagliptin and sulphonylureas preserved insulin secretion capacity.
Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), a hereditary cerebral small vessel disease caused by mutations in NOTCH3, is characterized by recurrent stroke without vascular risk factors, mood disturbances, and dementia. MRI imaging shows cerebral white matter (WM) hyperintensity, particularly in the external capsule and temporal pole. Missense mutations related to a cysteine residue in the 34 EGFr on the NOTCH3 extracellular domain (N3ECD) are a typical mutation of CADASIL. On the other hand, atypical mutations including cysteine sparing mutation, null mutation, homozygous mutation, and other associate genes are also reported. From the viewpoint of gain of function apart from Notch signaling or loss of function of Notch signaling, we review the research article about CADASIL and summarized the pathogenesis of small vessel, stroke, and dementia in this disease.
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