Background The role of Peroxiredoxin 6 (Prdx6) in brain ischemia remains unclear. Curcumin (Cur) treatment elicits neuroprotective effects against cerebral ischemic injury, and the associated mechanisms may involve Prdx6. In this study, we investigated whether Prdx6 and the transcription factor specific protein 1 (SP1) were involved in the antioxidant effect of Cur after stoke. Methods Focal cerebral ischemic injury was induced by transient middle cerebral artery occlusion for 2 hours in male Sprague-Dawley rats treated with or without Prdx6 siRNA. Expression of Prdx6 in the penumbra was assessed by Real-Time PCR (RT-PCR), Western blot analysis, and immunoflourescent staining. In addition, infarct volume, neurological deficit score, and oxidative stress were evaluated. Prdx6 levels were also determined in the presence and absence of SP1 antagonist mithramycin A (MTM-A). Results Cur treatment upregulated Prdx6 protein expression and the number of Prdx6-positive neuronal cells 24 hours after reperfusion. Cur treatment also attenuated oxidative stress and induced neuroprotective effects against ischemic damage, whereas the beneficial effects of Cur treatment were lost in animals treated with Prdx6-siRNA. Prdx6 upregulation by Cur treatment was abolished by SP1 antagonists MTM. Conclusions Prdx6 upregulation by Cur treatment attenuates ischemic oxidative damage through SP1 induction in rats after stroke. This represents a novel mechanism of Cur-induced neuroprotection against cerebral ischemia.
The role of lipocalin prostaglandin D2 synthase (L-PGDS) in brain ischemia has not been fully clarified to date. Vagus nerve stimulation (VNS) protects against cerebral ischemia/reperfusion (I/R) injury, but the mechanisms involved need further exploration. This study investigated the role of L-PGDS in cerebral I/R and whether this process was involved in the mechanism of VNS-mediated neuroprotection. Male Sprague-Dawley rats were pretreated with a lentiviral vector (LV) through intracerebroventricular injection, followed by middle cerebral artery occlusion (MCAO) and VNS treatment. The expression of L-PGDS in the peri-infarct cortex was examined. The localization of L-PGDS was determined using double immunofluorescence staining. Neurologic scores, infarct volume and neuronal apoptosis were evaluated at 24 h after reperfusion. The expression of apoptosis-related molecules was measured by western blot analysis. The expression of L-PGDS in the peri-infarct cortex increased at 12 h, reached a peak at 24 h after reperfusion, and lasted up to 3 days. VNS treatment further enhanced the expression of L-PGDS following ischemic stroke. L-PGDS was mainly expressed in neurons in the peri-infarct cortex. I/R rats treated with VNS showed better neurological deficit scores, reduced infarct volume, and decreased neuronal apoptosis as indicated by the decreased levels of Bax and cleaved caspase-3 as well as increased levels of Bcl-2. Strikingly, the beneficial effects of VNS were weakened after L-PGDS down-regulation. In general, our results suggest that L-PGDS is a potential mediator of VNS-induced neuroprotection against I/R injury.
BackgroundEnvironmental enrichment (EE) has a beneficial effect on some neuropsychiatric disorders. In this study, we aimed to investigate whether environmental enrichment could improve the spatial learning and memory in rats with vascular dementia (VaD) and the mechanism underpinning it.Material/MethodsBilateral common carotid occlusion (2-vessel occlusion [2VO]) was used to develop the animal model of vascular dementia. Adult male Sprague-Dawley (SD) rats were used in the experiment and were randomly divided into 4 groups: sham group, 2VO group, sham+EE group, and 2VO+EE group (n=19/group). The 2VO group and 2VO+EE group underwent bilateral common carotid occlusion. Two different housing conditions were used in this experiment: standard environment (SE) and enriched environment (EE). Rats in the sham group and 2VO group were put into SE cages for 4 weeks, while rats in the sham+EE group and 2VO+EE group were put in EE cages for 4 weeks. The Morris water maze and Y-maze were used to assess spatial learning and memory. Apoptosis was detected by TUNEL. The damage of neurons in the hippocampus was assessed by Nissl staining. The level of wnt pathway proteins were detected by Western blot.ResultsCompared with the 2VO group, the rats in the 2VO+EE group had better behavioral performance, fewer apoptotic neurons, and more surviving neurons. Western blot analysis showed that the levels of wnt pathway proteins were higher in 2VO+EE rats than in the 2VO group.ConclusionsEnvironmental enrichment can improve the spatial learning and memory in rats with vascular dementia, and the mechanism may be related to activation of the wnt/β-catenin signal pathway.
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