Guhong injection attenuates brain injury and promotes neuroprotection after acute ischemic stroke.

Abstract

Background and objectives: Guhong injection (GHI) has multiple components and generates diverse effects, and is mainly used in the treatment of acute ischemic stroke (AIS). The purpose of this study is to explore the multiple effects of GHI in AIS models in mice and the mechanism how they work together to affect the stroke outcome.

Methods: Middle cerebral artery occlusion (MCAO) and photothrombotic stroke models were established with GHI or vehicle. Neurological function assessment including the Modified Neurological Severity Score (mNSS) and rota-rod test, and relative cerebral blood flow were monitored at day 1 and day 3 after model establishment. Flow cytometry, 2, 3, 5-Triphenyltetrazolium chloride (TTC) staining, histology and immunofluorescence, Western blotting (WB) assay were performed at day 3.

Results: The mean mNSS score was lower and the latency to falling off the rota-rod was prolonged at day 3 in the GHI group. GHI reduced the relative infarct volume and increased the relative cerebral blood flow. The histopathological damage of ischemic core was significantly ameliorated in the GHI group. GHI decreased the Caspase-3⁺ cells and increased the MAP-2⁺ and Claudin-5⁺ cells. GHI increased the expression of Bcl-2 and the ratio of Bcl-2/Bax, and decreased the expression levels of Bax, Caspase-3 and Cleaved-Caspased-3. GHI reduced the microglia, decreased the IL-6 positive cells, TNF-α positive cells and increased TGF-β1 positive cells.

Conclusions: GHI alleviated brain injury and neurological deficits through improving cerebral blood circulation, attenuating neuronal apoptosis, reducing the disruption of blood-brain barrier (BBB) and decreasing neuroinflammation in MCAO and photothrombotic stroke models in mice. GHI has certain neuroprotective function to be applied to clinical use.