Mechanisms of sporadic cerebral small vessel disease: insights from neuroimaging

Abstract

The term "cerebral small vessel disease" (SVD) describes a range of neuroimaging, pathological and associated clinical features. The latter range from none, to discrete focal neurological symptoms (stroke), to insidious global neurological dysfunction and dementia. The public health burden is considerable. The pathogenesis is largely unknown. Although associated with vascular risk factors, and generally considered to result from an intrinsic cerebral arteriolar occlusive disease, the pathological processes leading to the arteriolar disease, how these result in brain disease, how SVD lesions contribute to neurological or cognitive symptoms and the relationship to risk factors, have been the subject of much speculation. Pathology often reflects end-stage disease making determination of the earliest stages difficult. Neuroimaging provides considerable insights: the small vessels are not easily seen themselves, but the effects of their malfunction on the brain can be tracked on detailed brain imaging. We review the growing evidence for the most likely mechanisms.

Albuminuria Increases the Risks for Both Alzheimer Disease and Vascular Dementia in Community‐Dwelling Japanese Elderly: The Hisayama Study

“…Several epidemiologic studies have demonstrated that both albuminuria and low eGFR had influence on the risk of clinical and subclinical cerebrovascular disease 32, 33, 34. Increased permeability of the blood–brain barrier, which is induced by endothelial dysfunction, causes white‐matter hyperintensities 35. Low eGFR is associated with the prevalence of silent brain infarcts and microbleeding 36.…”

Microglia and Monocyte-Derived Macrophages in Stroke

“…Overexpression of junctional adhesion molecule-1 leads to leukocyte adherence to microvasculature, resulting in hypertension in previously normotensive rats [222]. Hypertension causes activation of astrocytes and microglia and elevates expression of adhesion molecules in endothelial cells [223][224][225]. Microglia activation has been observed in angiotensin-II-induced hypertensive rats and intracerebroventricular administration of minocycline abrogated the angiotensin-II-induced hypertension [226].…”

Pericyte‐derived bone morphogenetic protein 4 underlies white matter damage after chronic hypoperfusion

“…Subcortical white matter changes caused by small vessel alterations are frequently observed in vascular cognitive impairment and are referred to as subcortical ‘small vessel disease (SVD)’ 39. Disturbances in cerebrospinal fluid production 40, cerebral edema 22, breakdown of the blood–brain barrier and increased permeability 21, 54, oxidative stress 4, and inflammation have been cited as important causes in the development of white matter changes 19. However, the exact mechanisms have yet to be fully elucidated.…”