Evaluation of Withania somnifera in a middle cerebral artery occlusion model of stroke in rats

Abstract

1. Stroke causes brain injury in millions of people worldwide each year. Despite the enormity of the problem, there is currently no approved therapy that can reduce infarct size or neurological disability. One of the approaches that can be used in limiting the neurological damage after stroke is the use of prophylactic treatment in patients with a high-risk of stroke. The present study was undertaken to investigate the effect of the Indian herbal plant Withania somnifera as a prophylactic treatment in the middle cerebral artery (MCA) occlusion model of stroke in rats. 2. Two groups of male Wistar rats were pretreated with a hydroalcoholic extract of W. somnifera (1 g/kg, p.o.) for 15 and 30 days. Thereafter, rats were subjected to focal ischaemia by occlusion of the MCA using an intraluminal thread. After 2 h MCA occlusion, reperfusion was allowed by retracting the thread. Animals were assessed for ischaemic changes using diffusion-weighted imaging 30 min after reperfusion. Twenty-four hours later, rats were subjected to motor performance tests and were subsequently killed for the estimation of the marker of oxidative stress malondialdehyde (MDA). The control group received vehicle and a similar protocol was followed. 3. Significant motor impairment, with elevated levels of MDA, was observed in vehicle-treated MCA-occluded rats. In addition, diffusion-weighted imaging showed increased signal intensity in the right hemisphere compared with the contralateral hemisphere. Treatment with W. somnifera for 15 days did not improve motor performance or decrease the elevated levels of MDA. However, when the pretreatment time of W. somnifera was increased to 30 days, it prevented motor impairment and significantly decreased the raised levels of MDA compared with vehicle-treated rats. In the W. somnifera (30 days)-pretreated group, the percentage hemispheric lesion area in diffusion-weighted imaging was significantly attenuated (17 ± 2%) compared with the vehicle-treated MCA-occluded group (30 ± 4%). 4. Because W. somnifera has been documented to have anti-oxidant properties, the protection afforded by W. somnifera could be due to its anti-oxidant effect. The present study provides first evidence of the effectiveness of an Indian herb in focal ischaemia.