Inhibiting leukocyte‐endothelial cell interactions by Chinese medicine Tongxinluo capsule alleviates no‐reflow after arterial recanalization in ischemic stroke.

Aims: Despite successful vascular recanalization in stroke, one‐fourth of patients have an unfavorable outcome due to no‐reflow. The pathogenesis of no‐reflow is fully unclear, and therapeutic strategies are lacking. Upon traditional Chinese medicine, Tongxinluo capsule (TXL) is a potential therapeutic agent for no‐reflow. Thus, this study is aimed to investigate the pathogenesis of no‐reflow in stroke, and whether TXL could alleviate no‐reflow as well as its potential mechanisms of action. Methods: Mice were orally administered with TXL (3.0 g/kg/d) after transient middle cerebral artery occlusion. We examined the following parameters: neurological function, no‐reflow, leukocyte‐endothelial cell interactions, HE staining, leukocyte subtypes, adhesion molecules, and chemokines. Results: Our results showed stroke caused neurological deficits, neuron death, and no‐reflow. Adherent and aggregated leukocytes obstructed microvessels as well as leukocyte infiltration in ischemic brain. Leukocyte subtypes changed after stroke mainly including neutrophils, lymphocytes, regulatory T cells, suppressor T cells, helper T type 1 (Th1) cells, Th2 cells, B cells, macrophages, natural killer cells, and dendritic cells. Stroke resulted in upregulated expression of adhesion molecules (P‐selectin, E‐selectin, and ICAM‐1) and chemokines (CC‐chemokine ligand (CCL)‐2, CCL‐3, CCL‐4, CCL‐5, and chemokine C‐X‐C ligand 1 (CXCL‐1)). Notably, TXL improved neurological deficits, protected neurons, alleviated no‐reflow and leukocyte‐endothelial cell interactions, regulated multiple leukocyte subtypes, and inhibited the expression of various inflammatory mediators. Conclusion: Leukocyte‐endothelial cell interactions mediated by multiple inflammatory factors are an important cause of no‐reflow in stroke. Accordingly, TXL could alleviate no‐reflow via suppressing the interactions through modulating various leukocyte subtypes and inhibiting the expression of multiple inflammatory mediators. [ABSTRACT FROM AUTHOR]