Abstract
Background: Stroke is a debilitating clinical disorder effecting millions of people worldwide. Despite advances in the understanding the pathophysiology of cerebral ischemia, no drug is available to protect the brain injury. Oxidative stress plays an important role in cerebral ischemia reperfusion injury. The present study evaluated the effect of an ester of fumaric acid, monomethy fumarate (MMF), on cerebral infarct and oxidative stress markers.
Methods: Experimental ischemic stroke was induced in male Sprague Dawley rats (260-290 g) by occluding middle cerebral artery using a 3.0 monofilament for 90 min followed by 24 h of reperfusion. Occlusion was confirmed by Laser Doppler flow meter. MMF (20 mg/kg) was administered in two divided doses, 30 min post ischemia and 5 min post reperfusion. Twenty four hours later, neurological deficits score and time spent on rota rod were evaluated. Cerebral infarct was estimated by T2 MR imaging at 7.0T animal MRI scanner. After MRI, rats were sacrificed; cortex and striatum were separated and homogenized. The levels of oxidative stress markers: reduced glutathione (GSH) and malondialdehyde (MDA) levels were estimated.
Results: Cerebral blood flow reduced by 82.8 percent of baseline on occlusion and on reperfusion 71.1 percent of blood flow was restored. Treatment with MMF significantly (p<0.01) improved neurological deficit score and the time spent on rota rod when compared to MCAo group. Further, in MMF group, cerebral infarct (23.5 percent) was significantly (p<0.05) reduced when compared to MCAo group (36.6 percent of ipsilateral area). In the MCAo group, the level of MDA was significantly increased whereas GSH level was significantly decreased when compared to sham group. MMF treatment significantly (p<0.05) increased the levels of GSH in cortex and striatum; and decreased (p<0.05) the elevated MDA levels in the cortex when compared to MCAo group.
Conclusion: These results suggest that MMF exhibits protection against MCAo model of ischemic stroke in rats. This beneficial effect may be through reduction of oxidative stress.
