Evaluation of the neuroprotective and antioxidant effects of Dorema aucheri extract on cerebral ischaemia-reperfusion injury in rats.

CONTEXT: The hydroalcoholic extract of Dorema aucheri Bilhar (Umbelliferae) (DA) leaves, a medicinal plant, has powerful antioxidant properties. OBJECTIVE: This study evaluates the neuroprotective effects of pre-treatment with DA leaves extract against cerebral ischaemia-induced brain injury through alteration of the antioxidant capacity. MATERIALS AND METHODS: The study was conducted in three groups of Wistar rats (N = 47) as follows; sham, control ischaemic and pre-treated ischaemic groups. Rats were administered a fresh hydroalcoholic extract of DA leaves at a dosage of 200 mg/kg/day for 14 days. Then, the middle cerebral artery (MCA) of the right hemisphere was occluded for 90 min to achieve cerebral ischaemia. After 24 h reperfusion, cerebral infarction and superoxide dismutase (SOD) and catalase activities, as well as malondialdehyde (MDA), glutathione, and NOx contents were determined in the right hemispheres. RESULTS: Occlusion of the right MCA caused noticeable cerebral infarction (298 ± 21 mm3) in control ischaemic group, but pre-treatment with DA extract considerably attenuated it (92 ± 14 mm3) in the pre-treated ischaemic group. DA extract significantly decreased the levels of MDA by 28% and NOx by 11% in pre-treated ischaemic group compared to the control ischaemic group. DA extract also enhanced glutathione content by 7%, SOD activity by 16% and catalase activity by 46% in pre-treated ischaemic rats compared to control ischaemic rats. DISCUSSION AND CONCLUSIONS: DA is able to improve the antioxidant capacity and injuries of ischaemic brain. It is proposed as a neuroprotectant following cerebral ischaemia to decrease the injuries of ischaemic stroke.

Bone marrow-derived mesenchymal stem cell and simvastatin treatment leads to improved functional recovery and modified c-Fos expression levels in the brain following ischemic stroke.

OBJECTIVES: The beneficial outcomes of bone marrow-derived mesenchymal stem cell (BMSC) treatment on functional recovery following stroke has been well established. Furthermore, 5-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors have also been shown to increase neuronal survival and promote the movement of BMSCs towards the sites of inflammation. However, the precise mechanisms mediating the improved neurological functional recovery in stoke models following a combination treatment of Simvastatin and BMSCs still remained poorly understood. MATERIALS AND METHODS: Here, an embolic stroke model was used to experimentally induce a focal ischemic brain injury by inserting a preformed clot into the middle cerebral artery (MCA). Following stroke, animals were treated either with an intraperitoneal injection of Simvastatin, an intravenous injection of 3 ×106 BMSCs, or a combination of these two treatments. RESULTS: Seven days after ischemia, the combination of Simvastatin and BMSCs led to a significant increase in BMSC relocation, endogenous neurogenesis, arteriogenesis and astrocyte activation while also reducing neuronal damage when compared to BMSC treatment alone (P<0.001 for all). In addition, based on western blot analysis, following stroke there was a significant decrease in c-Fos expression (P<0.001) in the combination treatment group. CONCLUSION: These results further demonstrate the synergistic benefits of a combination treatment and help to improve our understanding of the underlying mechanisms mediating this beneficial effect.