From mechanism to classification: Understanding a novel model of cerebral small vessel disease

Abstract

The studies explored cerebral small vessel disease (cSVD), emphasizing the need for precise classification to improve prevention and intervention strategies. Kang et al. introduced an intra-cisterna-magna bevacizumab injection (ICM-BI) model in mice, which induced tight junction loss, microbleeds, and amyloid deposits. However, bevacizumab's low affinity for murine vascular endothelial growth factor raises questions about its mechanism of action, suggesting potential off-target effects. While most cSVD models mimic arteriolosclerosis (type 1) or genetic variants (types 2 and 3), the ICM-BI model represents a novel approach to studying immune-mediated cSVD (type 4). The complexity and variability of cSVD remain significant research challenges.

Keywords: Cerebral small vessel disease; classification; in vivo model; interferon; neuroinflammation.

Figure 1.

Bevacizumab injection induced cerebral small vessel disease in mice. Intra-cisterna-magna bevacizumab injection caused loss of tight junction ZO-1. It reduced the diameter of small blood vessels, cerebral microbleeds, amyloid peptide deposits, and functional impairments resembling cerebral small vessel disease in C57/Bl6 mice. A possible mechanism for this alternation is mediated by interferon and neuroinflammation by injection.