Abstract
Ischemic stroke, an intractable neurovascular disease with high lethality, disability and recurrence rates, poses a serious challenge to human health. The only effective treatment for acute stroke is reperfusion therapy. However, the inflammatory response caused by reperfusion therapy often aggravates secondary brain tissue damage, which greatly affects the treatment effect. Currently, therapeutic options for reperfusion injury remain unsatisfactory, and neuroprotective options are lacking. The inhibition of microglia polarization and promotion of neovascular maturation are essential for reestablishing the integrity of the BBB. Specifically, McM/RNPs effectively inhibited the secretion of pro-inflammatory factors such as tumour necrosis factor-α (TNF-α) and interleukin-6 (IL-6) and promoted the release of anti-inflammatory and neuroprotective factors such as interleukin-10 (IL-10), vascular endothelial growth factor-A (VEGF-A), and brain-derived neurotrophic factor (BDNF). This effect not only alleviated the inflammatory response but also promoted the expression of endothelial tight junction proteins (such as ZO-1 and Claudin 5), thereby enhancing the integrity of the BBB. Furthermore, McM/RNPs exerted multiple effects, such as promoting neuronal survival, regulating pericyte function, and accelerating the maturation of the neovasculature, which are essential for repairing the damaged BBB. Through the multi-functional effects of anti-inflammation, anti-apoptosis and pericyte regulation, the McM/RNPs nanosystem successfully maintained the stability of the intracerebral environment, providing novel ideas and strategies for the clinical treatment of reperfusion injury in ischemic stroke.