Neuroprotective effects of salvianolic acids combined with Panax notoginseng saponins in cerebral ischemia/reperfusion rats concerning the neurovascular unit and trophic coupling

Abstract

Background

The neurovascular unit (NVU) and neurovascular trophic coupling (NVTC) play a key regulatory role in brain injury caused by ischemic stroke. Salvianolic acids (SAL) and Panax notoginseng saponins (PNS) are widely used in China to manage ischemic stroke. Neuroprotective effects of SAL and PNS, either taken alone or in combination, were examined in this research.

Methods

Wistar rats were randomly divided into the following groups: Sham group (Sham), cerebral ischemia/reperfusion group (I/R), I/R with SAL group (SAL), I/R with PNS group (PNS), I/R with SAL combined with PNS (SAL + PNS), and I/R with edaravone group (EDA). Treatment was administered once daily for two days after modeling of middle cerebral artery occlusion/reperfusion (MCAO/R).

Results

Compared with the I/R group, SAL, PNS, or SAL + PNS treatment reduced infarct size, improved neurological deficit score, reduced Evans blue extravasation, increased expression of CD31 and tight junction proteins (TJs), including zonula occludens-1 (ZO-1), zonula occludens-2 (ZO-2), and junctional adhesion molecule-1 (JAM-1). Furthermore, SAL, PNS, or SAL + PNS suppressed the activations of microglia and astrocyte and led to the amelioration of neuron and pericyte injury. Treatment also inhibited NVU dissociation of GFAP/PDGFRβ and Collagen IV/GFAP while upregulated the expression level of BDNF/TrkB and BDNF/NeuN.

Conclusions

SAL and PNS have significantly remedied structural and functional disorders of NVU and NVTC in I/R injury. These effects were more pronounced when SAL and PNS were combined than when used separately.