Microangiopathies of the human brain b immunohistochemical studies on extracellular matrix components in arterial vessels and endothelin

Sammanfattning: Microangiopathies may cause ischemic brain lesions and are of fundamental importance in vascular dementia. Risk factors include high age, hypertension, diabetes and Alzheimer's disease. In addition, recent studies have focused on autosomal dominant types of arteriopathy causing leukoencephalopathy,psychiatric disturbances, stroke and dementia (CADASIL). This thesis concerns various collagens andbasal lamina components which are deposited in vascular walls of cases presenting cerebral microangiopathy. In addition, endothelin-like immunoreactivity has been studied in CADASIL cases andsome other brain diseases.CADASIL cases described by Sourander and Wålinder (1977) were re-investigated. Those with longduration of the disease presented marked expression of fibrillary collagen types I, Ill, V and VI and of thebasal lamina components, collagen type IV and laminin. Deposits appeared also in non-familial casespresenting hyalinosis and in cases with the Binswanger type of leukoencephalopathy. Media degeneration and deposition of fibrillary collagens will in CADASIL, Binswanger's disease and hyalinosis graduallytransform the vessels to obliterated stiff tubings which can not properly regulate blood flow. On the otherhand, many vessels in cases with amyloid angiopathy did not show accumulations of collagens I, Ill and V. Such vessels may be more prone to rupture and cerebral hemorrhages than those in which fibrillarycollagens have been deposited. Finally, studies on CADASIL cases, other cases with brain infarcts, lacunas and Alzheimer's disease demonstrated an endothelin-like immunoreactivity in reactive perivascular astrocytes. The idea was therefore proposed that during the course of brain lesions activated astrocytes start a production of endothelin-1 which after release may reach nearby microvessels and inducevaseconstriction leading to additional brain injury.Structural as well as humoral factors are both most likely important for the production of brain lesionsin cases presenting cerebral microangiopathies.