Elsevier

Brain Research

Volume 1268, 1 May 2009, Pages 174-180
Brain Research

Research Report
Oxymatrine protects rat brains against permanent focal ischemia and downregulates NF-κB expression

https://doi.org/10.1016/j.brainres.2009.02.069Get rights and content

Abstract

Background

Oxymatrine is proven to protect ischemic and reperfusion injury in liver, intestine and heart, this effect is via anti-inflammation and anti-apoptosis. Whether this protective effect applies to ischemic injury in brain, we therefore investigate the potential neuroprotective role of oxymatrine and the underlying mechanisms.

Methods

Male, Sprague–Dawley rats were randomly assigned to four groups: permanent middle cerebral artery occlusion (pMCAO), high dose (pMCAO + oxymatrine 120 mg/kg), low dose (pMCAO + oxymatrine 60 mg/kg) and sham operated group. We used a permanent middle cerebral artery occlusion model and administered oxymatrine intraperitoneally immediately after cerebral ischemia and once daily on the following days. At 24 h after MCAO, neurological deficit was evaluated using a modified six point scale; brain water content was measured; NF-κB expression was measured by immunohistochemistry, Western blotting and RT-PCR. Infarct volume was analyzed with 2, 3, 5-triphenyltetrazolium chloride (TTC) staining at 72 h.

Results

Compared with pMCAO group, neurological deficit in high dose group was improved (P < 0.05), infarct volume was decreased (P < 0.001) and cerebral edema was alleviated (P < 0.05). Consistent with these indices, immunohistochemistry, Western blot and RT-PCR analysis indicated that NF-κB expression was significantly decreased in high dose group. Low dose of oxymatrine did not affect NF-κB expression in pMCAO rats.

Conclusions

Oxymatrine reduced infarct volume induced by pMCAO, this effect may be through the decreasing of NF-κB expression.

Introduction

Ischemic stroke remains a leading cause of death and disability worldwide. In acute stroke, neuron apoptosis and inflammation play an important role in tissue loss and neurological deficit. Oxymatrine (OMT) is the major quinolizidine alkaloid from the root of Sophora flavescens Ait (kushen). The structure of OMT is clear as shown in Fig. 1. It has been proved that OMT has anti-inflammatory, anti-apoptosis, anti-tumor, anti-viral and anti-arrhythmic effects. OMT also exerts a protective effect on ischemia or ischemia/reperfusion damage in liver, intestine and heart (Jiang et al., 2005, Zhao et al., 2008, Hong-Li et al., 2008). In the colitis induced by dextran sulfate sodium, OMT ameliorates the colonic inflammation through reducing expression of NF-κB in colonic mucosa (Zheng et al., 2005).

Nuclear factor-kappa B (NF-κB) is a ubiquitously expressed transcription factor that regulates expression of genes involved in inflammation, cell survival and apoptosis (Małek et al., 2007). There are many evidences that NF-κB is upregulated following ischemia (Terai et al., 1996, Gabriel et al., 1999). Also many data suggest that inhibition of NF-κB reduces infarction volume and develops less ischemic damage in permanent ischemia especially; maybe NF-κB antagonists are therapeutic agents for stroke (Shen et al., 2003, Schneider et al., 1999, Ueno et al., 2001, Xu et al., 2002, Nurmi et al., 2004a, Nurmi et al., 2004b).

The aim of this study was to investigate whether OMT has a neuroprotective effect in the rat model of permanent middle cerebral artery occlusion (pMCAO) and the potential mechanisms for its neuroprotection.

Section snippets

OMT treatment and neurological deficit after pMCAO in rats

Neurological deficit was examined and scored on a 6-point scale and Mann–Whitney U test analysis was conducted. Neurological deficit scores were significantly decreased by OMT at a dose of 120 mg/kg (P < 0.05) versus saline-treated pMCAO group. At a dose of 60 mg/kg, OMT reduced the scores, but did not reach a significance level (Fig. 2).

Effect of OMT on infarct volume in pMCAO rats

No infarction was observed in sham operated group, Fig. 3 displayed the image of the untreated and treated animals at 72 h after cerebral ischemia. In pMCAO

Discussion

Our study provided evidence that OMT was a potent neuroprotectants in brain ischemia. Here, our study showed that administration of 120 mg/kg OMT was sufficient to provide significant neuroprotection against neurological injury induced by pMCAO. We supported this finding by both histological and neurological data: a reduction in the brain infarct volume and an attenuation of the neurological deficit, both of which are clinical features and related with the quality of life after stroke. Also the

Animals

Male Sprague–Dawley rats, weighing 260 to 280 g were provided by Hebei Medical University. The protocol was approved by the institutional animal care and use committee and the local experimental ethics committee. Rats were kept under a 12/12 h light/dark cycle and given free access to food and water. The animals were randomly divided into 4 groups (n = 15 for each group): pMCAO group, high dose group (animals with pMCAO and 120 mg/kg OMT treatment), low dose group (animals with pMCAO and 60 mg/kg

Acknowledgments

This work was funded by Hebei Province, No.:C2006000915; we thank technician Ruichun Liu and Hongran Wu for their technical assistance and Dr. Yi Yang, Dr. Litao Li, Dr. Jing Yin and Dr. Yansu Guo for providing valuable suggestions.

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