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.

Fullerenol Nanoparticles Decrease Blood-Brain Barrier Interruption and Brain Edema during Cerebral Ischemia-Reperfusion Injury Probably by Reduction of Interleukin-6 and Matrix Metalloproteinase-9 Transcription.

BACKGROUND: The present study aimed to examine the protective role of fullerenol nanoparticles against blood-brain barrier (BBB) interruption and brain edema during cerebral ischemia-reperfusion injury probably by reduction of interleukin-6 (IL-6) and matrix metalloproteinase-9 (MMP-9) transcription. METHODS: The male Wistar rats (weighting 280-320 g) were randomly assigned into four groups as follows: sham, control ischemic, pretreated ischemic, and posttreated ischemic groups. Cerebral ischemia-reperfusion (IR) injury was performed by occlusion of middle cerebral artery (MCA) for 90 minutes followed by twenty-four hours reperfusion. Rats were administered fullerenol 5mg/kg, intraperitoneally, 30 minutes before induction of IR in pretreated ischemic group and immediately after termination of MCA occlusion in posttreated ischemic group. After twenty-four hours reperfusion, the method of Evans blue dye extravasation (EBE) and RT-PCR were used for determination of BBB permeability and mRNA expression levels of MMP-9 and IL-6, respectively. Neuronal deficit score (NDS) and edema of the ischemic hemispheres were also evaluated. RESULTS: MCA occlusion increased NDS in control ischemic rats (3.16 ± 0.16) with concomitant increase in EBE (15.30 ± 3.98µg/g) and edema (3.53 ± 0.50%). Fullerenol in both pretreated and posttreated ischemic groups reduced NDS (36% and 68%, respectively), EBE (89% and 91%, respectively) and edema (53% and 81%, respectively). Although MCA occlusion increased the mRNA expression levels of MMP-9 and IL-6 in ischemic hemispheres, fullerenol in both treatment groups noticeably decreased the mRNA expression levels of these genes. CONCLUSION: In conclusion, fullerenol nanoparticles can protect BBB integrity and attenuate brain edema after cerebral ischemia-reperfusion injury possibly by reduction of IL-6 and MMP-9 transcription.

Captopril and Valsartan May Improve Cognitive Function Through Potentiation of the Brain Antioxidant Defense System and Attenuation of Oxidative/Nitrosative Damage in STZ-Induced Dementia in Rat.

Purpose: Previous findings have shown the crucial roles of brain renin-angiotensin system (RAS) in pathogenesis of Alzheimer's disease (AD). Since RAS inhibitors may have beneficial effects on dementia and cognitive function in elderly people, the aim of present study was to examine the neuroprotective actions of captopril and valsartan on memory function and neuronal damage in experimental model of AD. Methods: Adult forty male Wistar rats (220-280g) were randomly divided into 5 groups; Control, Vehicle, Alzheimer and treatment groups. AD was induced by the injections of streptozotocin (3mg/kg, bilateral intracerebroventricular) at days 1&3. Treated rats received orally captopril (50mg/kg/day) and valsartan (30mg/kg/day). Memory function and histological assessments were done at termination of experiment. Finally, superoxide dismutase (SOD) and catalase (CAT) activities as well as malondialdehyde (MDA) and NOx contents were determined. Results: There was a significant increase in the mean value of latency in Alzheimer group (66%). Captopril and valsartan considerably decreased this value in both treatment groups (45% and 72%, respectively). In Alzheimer group the activities of brain's SOD and CAT reduced (40% and 47%, respectively) in accompany with an increase in MDA and NOx contents (49% and 50%, respectively). Captopril and valsartan significantly increased the activities of brain's SOD and CAT concomitant reduction in MDA and NOx contents. Also, histopathological damages noticeably decreased in both treatment groups. Conclusion: Our findings indicate that RAS inhibition by using captopril and valsartan potentiates the antioxidant defense system of brain and reduces oxidative/nitrosative stress in accompany with neuronal damage during AD.