Dual role of innate immune activation in cerebral small vessel disease

Cerebral small vessel disease (CSVD) is an age-related cerebrovascular disease characterized by repeated strokes and accelerated neurodegeneration. The immune inflammatory mechanism is at the core of its development. The disruption of the blood-brain barrier (BBB) instigates a state of chronic inflammation and leukocyte infiltration. The innate immune system is the body's primary defense against infection and may exhibit a dual role in CSVD. It has been observed that peripheral immune cells, including but not limited to neutrophils and monocytes, have the capacity to exacerbate brain inflammation. However, it is important to note that certain phenotypes may offer neuroprotection. The complement system and inflammasome represent pivotal components of innate immunity. Among them, NLRP3 may be associated with the pathogenesis of CSVD. In the central nervous system (CNS), microglia, as resident macrophages, have been shown to mediate immune responses and may acquire immune memory. Neuroinflammation is a pivotal pathological factor in CNS diseases, exerting both beneficial and harmful effects. The imaging manifestations of CSVD, including white matter hypersignal (WMH) and perivascular space (PVS), have been proven to be associated with different neuroinflammatory spectra. Advances in comprehension of the interaction between central and peripheral immune cells have yielded insights into the intricate mechanisms of CSVD, underscoring the imperative for targeted immunomodulatory interventions. It is recommended that subsequent research endeavours concentrate on elucidating the spatiotemporal dynamics of immune cell participation and identifying novel biomarkers for early diagnosis and treatment monitoring.