Chinese medicine Tongxinluo capsule alleviates cerebral microcirculatory disturbances in ischemic stroke by modulating vascular endothelial function and inhibiting leukocyte-endothelial cell interactions in mice: A two-photon laser scanning microscopy study.

ABSTRACT

OBJECTIVE: The aim of this study was to examine the effect of TXL, a Chinese medicine prescription, on cerebral microcirculatory disturbances after pMCAO in mice using TPLSM and further explore the underlying mechanisms. METHODS: Adlut male C57BL/6J mice were subjected to pMCAO and orally administered with TXL (3.0, 1.5 and 0.75 g/kg/d) at 1, 3, and 21 hours after pMCAO. The following parameters were examined at 6 and 24 hours after pMCAO neurological deficits, infarct volume, BBB permeability, cerebral microvessel structure, brain microcirculation (TPLSM imaging), vasoactive factors, and adhesion molecules. RESULTS: TXL improved neurological deficits, reduced infarct volume, attenuated BBB disruption, protected cerebral microvessel structure, increased cerebral capillary flow velocity and volume flux, and inhibited leukocyte-endothelial cell interactions at 6 or 24 hours after pMCAO. The therapeutic efficacy was exerted in a dose-dependent manner. Further study revealed that TXL (high dose) regulated the expression of PGI2, TXA2, and ET-1, and suppressed ICAM-1 and P-selectin. CONCLUSIONS: TXL alleviates cerebral microcirculatory disturbances against ischemic injury by modulating endothelial function and inhibiting leukocyte-endothelial cell interactions. These effects are associated with regulating the expression of PGI2, TXA2, and ET-1, and suppressing ICAM-1 and P-selectin expression.