Cerebroprotective effect of pterostilbene against global cerebral ischemia in rats.
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ABSTRACT: Aim of the study
The role of pterostilbene against induced neurobehavioral alterations in global cerebral ischemia-reperfusion and oxidative damage was studied.Materials and methods
Male SD rats (180-200 g) were exposed for 30 min to bilateral carotid artery occlusion accompanied by 60 min reperfusion to cause cerebral injury. Pretreatment with pterostilbene (200 and 400 mg/kg, orally) was given to the animals for ten days followed by ischemia-reperfusion injury. Various behavioral tests (locomotor activity, neurological score, transfer latency, hanging wire test) were studied. The brain tissues of animals were used for both the biochemical parameters (lipid peroxidation, reduced glutathione, superoxide dismutase, catalase activity) and histopathological study.Result
The pterostilbene as given orally significantly improved neurobehavioral alterations compared to control ischemia-reperfusion. Treatment with pterostilbene (200, and 400 mg/kg, orally) also significantly attenuated oxidative damage as indicated by reduced lipid peroxidation, nitrite concentration, restored reduced glutathione, and catalase activity as compared to control (ischemia-reperfusion) animals. Overall, pterostilbene treated animals showed non significant histological alteration as compared to ischemia-reperfusion control.Conclusion
This work suggests the beneficial effect of pterostilbene and its therapeutic potential against reperfusion-induced ischemia and associated behavioral changes in rats due to the stabilization of DNA damage with significant free radical scavenging properties.
SUBMITTER: Khan MM
PROVIDER: S-EPMC8150920 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Global brain ischemia/reperfusion induces neuronal damage in vulnerable brain regions, leading to mitochondrial dysfunction and subsequent neuronal death. Induction of neuronal death is mediated by release of cytochrome c (cyt c) from the mitochondria though a well-characterized increase in outer mitochondrial membrane permeability. However, for cyt c to be released it is first necessary for cyt c to be liberated from the cristae junctions which are gated by Opa1 oligomers. Opa1 has two known functions: maintenance of the cristae junction and mitochondrial fusion. These roles suggest that Opa1 could play a central role in both controlling cyt c release and mitochondrial fusion/fission processes during ischemia/reperfusion. To investigate this concept, we first utilized in vitro real-time imaging to visualize dynamic changes in mitochondria. Oxygen-glucose deprivation (OGD) of neurons grown in culture induced a dual-phase mitochondrial fragmentation profile: (i) fragmentation during OGD with no apoptosis activation, followed by fusion of mitochondrial networks after reoxygenation and a (ii) subsequent extensive fragmentation and apoptosis activation that preceded cell death. We next evaluated changes in mitochondrial dynamic state during reperfusion in a rat model of global brain ischemia. Evaluation of mitochondrial morphology with confocal and electron microscopy revealed a similar induction of fragmentation following global brain ischemia. Mitochondrial fragmentation aligned temporally with specific apoptotic events, including cyt c release, caspase 3/7 activation, and interestingly, release of the fusion protein Opa1. Moreover, we uncovered evidence of loss of Opa1 complexes during the progression of reperfusion, and electron microscopy micrographs revealed a loss of cristae architecture following global brain ischemia. These data provide novel evidence implicating a temporal connection between Opa1 alterations and dysfunctional mitochondrial dynamics following global brain ischemia.
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Project description:BackgroundParicalcitol is known to attenuate ischemic-reperfusion injury of various organs. However, it is not known whether paricalcitol prevents neuronal injury after global cerebral ischemia. The purpose of this study is to investigate the neuroprotective effect of paricalcitol in a rat model of transient global cerebral ischemia.MethodsThis is a prospective, randomized experimental study. Male Sprague-Dawley rats that survived 10?min of four-vessel occlusion were randomly assigned to two treatment groups: one group was treated with paricalcitol 1??g/kg IP, and the other was given an equivalent volume of normal saline IP. Drugs were administered at 5?min, 1?day, 2?days, and 3?days after ischemia. Neurologic function was assessed at 2?h, 1?day, 2?days, 3?days, and 4?days after ischemia. We tested motor function 3?days after ischemia using the rotarod test. Also, we tested memory function 4?days after ischemia using the passive avoidance test. We assessed neuronal degeneration in the hippocampus of surviving rats 4?days after ischemia.ResultsEight rats were allocated to each group. No significant differences were found between the groups in terms of survival rate, motor coordination, or memory function. The neurological function score 2-h post-ischemia was significantly higher in the paricalcitol group (p = 0.04). Neuronal degeneration was significantly less in the paricalcitol group compared with the control group (p = 0.01).ConclusionsParicalcitol significantly attenuated neuronal injury in the hippocampus. Although motor coordination, memory function, and survival rate were not significantly improved by paricalcitol treatment in this study, paricalcitol remains a potential neuroprotective drug after global cerebral ischemia.
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