Stases are associated with blood-brain barrier damage and a restricted activation of coagulation in SHRSP

Abstract

Cerebral small vessel disease (CSVD) is a chronically proceeding pathology of small brain vessels associated with white matter lesions, lacunar infarcts, brain atrophy and microbleeds. CSVD leads to slowly increasing cognitive and functional deficits but may also cause stroke-like symptoms, if vessels in critical brain areas are affected. Spontaneously hypertensive stroke-prone rats (SHRSP) exhibit several vascular risk factors, develop infarcts and hemorrhages and therefore represent a relevant model for the study of CSVD. Using this animal model, we recently demonstrated that intravasal accumulations of erythrocytes, we interpreted as stases, stand at the beginning of a pathological vascular cascade. After stases microbleeds occur, which are followed by reactive microthromboses. Bleeds and thromboses finally cause hemorrhagic infarcts. Immunohistochemical stainings show, that plasma proteins like IgG are deposited in the walls of vessels affected by stases. Further, we found small clots and thread-shaped aggregations of thrombocytes as well as thread-shaped structures of von Willebrand-Factor within stases. Thus, we conclude that blood-brain barrier damages occur in the neighborhood of stases and stases seem to be associated with a restricted activation of blood coagulation without formation of obstructive thromboses. Finally, we demonstrate that small vessel damage rarely appears in the cerebellum. Even animals with multiple cerebral infarcts may be free of any cerebellar vascular pathology.