The combination of Ling Jiao Gou Teng decoction and ischemic preconditioning protect against cerebral ischemic reperfusion injury in rats by protecting the blood brain barrier

Abstract

Ling Jiao Gou Teng decoction (LJGT) is a famous traditional Chinese medicine formula for treating ischemic stroke. It is not known whether the combination of LJGT and ischemic preconditioning can enhance the neuroprotective effect of cerebral ischemia and thus alleviate the neurological damage caused by subsequent ischemic attacks. In this article, we used middle cerebral artery occlusion (MCAO) rats model to evaluate the effects of LJGT associate to remote ischemic preconditioning (RIPC) on cerebral ischemic reperfusion (I/R) injury and its underlying molecular mechanisms. The results showed that LJGT and RIPC pretreatment significantly reduced the cerebral edema, cerebral infarct volume and the neurological deficit scores. Meanwhile, LJGT and RIPC could protect the blood brain barrier (BBB) and improve the morphology and ultrastructure of ischemic penumbra brain tissue. In addition, LJGT and RIPC pretreatment significantly inhibited the expressions of mRNA and protein of MMP-2 and MMP-9, while it strengthened the expressions of occlusion, ZO-1 and TIMP-1. Moreover, the effects of LJGT and RIPC pretreatment on the expression of these genes were better than that in the group treated with LJGT or RIPC alone. The results suggested that LJGT and RIPC preconditioning had a neuroprotective effect on cerebral ischemia/reperfusion injury, and the underlying mechanism was related to protecting BBB integrity through inhibiting the production of MMP-2 and MMP-9 and activating the expressions of occlusion, ZO-1, and TIMP-1.

Keywords

• Cerebral edema
• BBB
• Cerebral ischemia reperfusion
• Ling Jiao Gou Teng decoction
• Remote ischemic preconditioning