The role of blood-brain barrier disruption in spontaneous intracerebral haemorrhage and small vessel disease

Abstract

Spontaneous intracerebral haemorrhage (ICH) is a detrimental type of stroke leading to high disability and mortality rates. Despite many attempts at unraveling its etiology the exact pathogenesis remains elusive. Interestingly, emerging evidence suggests that blood-brain barrier (BBB) disruption may be an important trigger in the vessel rupture cascade that characterizes spontaneous ICH. In order to clarify the possible pathogenic role of BBB damage in ICH, this systematic review lines out current evidence on BBB disruption in spontaneous ICH and its two main underlying small vessel disease processes, cerebral amyloid angiopathy (CAA) and hypertensive vasculopathy (HV). 59 human and animal studies were identified, including six studies that investigated BBB integrity in ICH, 12 studies that assessed this in CAA, and 41 studies investigating this in HV. Based on the literature it can be concluded that BBB disruption is apparent in spontaneous ICH and originates in associated small vessel disorders. Limited evidence suggests that heterogeneous mechanisms may underlie BBB alterations in relation to amyloid angiopathy and hypertension. Mediating factors may affect BBB integrity including genetic predispositions, dietary influences, and aging. Also, a universal relationship between BBB disruption and neuro-inflammation seems to be apparent. Future research should emphasize reliable classification of patients according to type of vasculopathy and make use of translational research approaches to unravel possible distinct mechanisms leading to HV- and CAA-related ICH.