Emerging Role of Immunity in Cerebral Small Vessel Disease

Cerebral small vessel disease (CSVD) is one of the main causes of vascular dementia in older individuals. Apart from risk containment, efforts to prevent or treat CSVD are ineffective due to the unknown pathogenesis of the disease. CSVD, a subtype of stroke, is characterized by recurrent strokes and neurodegeneration. Blood-brain barrier (BBB) impairment, chronic inflammatory responses, and leukocyte infiltration are classical pathological features of CSVD. Understanding how BBB disruption instigates inflammatory and degenerative processes may be informative for CSVD therapy. Antigens derived from the brain are found in the peripheral blood of lacunar stroke patients, and antibodies and sensitized T cells against brain antigens are also detected in patients with leukoaraiosis. These findings suggest that antigen-specific immune responses could occur in CSVD. This review describes the neurovascular unit features of CSVD, the immune responses to specific neuronal and glial processes that may be involved in a distinct mechanism of CSVD, and the current evidence of the association between mechanisms of inflammation and interventions in CSVD. We suggest that autoimmune activity should be assessed in future studies; this knowledge would benefit the development of effective therapeutic interventions in CSVD.