Androgen Receptor Involvement In Ischemic Preconditioning During Cerebral Ischemia-Reperfusion Injury
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Author:
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PRABHAT SINGH, BHUPESH SHARMA
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Abstract:
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Objective: Ischemic preconditioning (IPC) is a milestone concept in the cerebrovascular sciences that has opened a new phase in the area of cerebral protection. Protective mechanisms involved in preconditioning are a serious challenge in the research field of ischemic stroke. In this research, we explored the role of androgen receptors (ARs) in IPC induced beneficial effects in ischemia-reperfusion induced cerebral injury.
Materials and Methods: Rats were subjected to global cerebral ischemia-GCI (17 min) followed by reperfusion (24 h). Immediately before GCI, IPC was applied by subjecting both carotid arteries to three cycles of ischemia (1 min) with recurrent reperfusion (1 min). Animals were revealed to Morris water maze (cognition), rota-rod, inclined-beam-walk, lateral-push, and hanging-wire test (motor functions). TTC staining (cerebral infarction), oxidative damage markers (lipid peroxidation, glutathione), inflammation (myeloperoxidase), and cholinergic function (acetylcholinesterase) were also assessed.
Results: IPC significantly reduced cerebral infarct size, motor, and cognitive dysfunction along with biochemical impairments (reduced activity of lipid peroxides, myeloperoxidase, and acetylcholinesterase as well as increased glutathione content). Testosterone pretreatment (1 h-before cerebral ischemia) mimicked the neuroprotective impact of IPC. However, pretreatment with flutamide (ARs antagonist) abolished neuroprotection provided by IPC.
Conclusion: IPC can provide neuroprotection from cerebral injury caused by cerebral ischemia-reperfusion, by modulating ARs.
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Keyword:
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Testosterone, flutamide, cerebral ischemia, brain injury, oxidative damage, cognitive dysfunction.
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EOI:
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-
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DOI:
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https://doi.org/10.31838/ijpr/2020.SP2.053
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