SIRT1 activation by resveratrol reduces brain edema and neuronal apoptosis in an experimental rat subarachnoid hemorrhage model

Qian,Cong; Jin,Jianxiang; Chen,Jingyin; Li,Jianru; Yu,Xiaobo; Mo,Hangbo; Chen,Gao

doi:10.3892/mmr.2017.7773

SIRT1 activation by resveratrol reduces brain edema and neuronal apoptosis in an experimental rat subarachnoid hemorrhage model

Authors:
- Cong Qian
- Jianxiang Jin
- Jingyin Chen
- Jianru Li
- Xiaobo Yu
- Hangbo Mo
- Gao Chen
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Affiliations: Department of Neurological Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310009, P.R. China
Published online on: October 12, 2017 https://doi.org/10.3892/mmr.2017.7773
Pages: 9627-9635

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Abstract

Early brain injury is considered to be a major risk that is related to the prognosis of subarachnoid hemorrhage (SAH). In SAH model rats, brain edema and apoptosis have been closely related with death rate and neurological function. Sirtuin 1 (SIRT1) was reported to be involved in apoptosis in cerebral ischemia and brain tumor formation through p53 deacetylation. The present study aimed to evaluate the role of SIRT1 in a rat endovascular perforation model of SAH. The SIRT1 activator resveratrol (RES) was administered 48 h prior to SAH induction and the SIRT1 inhibitor Sirtinol (SIR) was used to reverse the effects of RES on SIRT1 expression. Mortality rate, neurological function and brain water content were measured 24 h post‑SAH induction. Proteins associated with the blood brain barrier (BBB), apoptosis and SIRT1 in the cortex, such as zona occludens 1 (ZO‑1), occludin, claudin‑5, SIRT1, p53 and cleaved caspase3 were investigated. mRNA expression of the p53 downstream molecules including Bcl‑associated X protein, P53 upregulated modulator of apoptosis, Noxa and BH3 interacting‑domain death agonist were also investigated. Neuronal apoptosis was also investigated by immunofluorescence. RES pretreatment reduced the mortality rate and improved neurological function, which was consistent with reduced brain water content and neuronal apoptosis; these effects were partially reversed by co‑treatment with SIR. SIRT1 may reduce the brain water content by improvement of dysfunctional BBB permeability, and protein analysis revealed that both ZO‑1, occludin and claudin‑5 may be involved, and these effects were reversed by SIRT1 inhibition. SIRT1 may also affect apoptosis post‑SAH through p53 deacetylation, and the analysis of p53 related downstream pro‑apoptotic molecules supported this hypothesis. Localization of neuron specific apoptosis revealed that SIRT1 may regulate neuronal apoptosis following SAH. SIRT1 may also ease brain edema and neuronal protection through BBB improvement and p53 deacetylation. SIRT1 activators such as RES may have the potential to improve the prognosis of patients with SAH and clinical research should be investigated further.

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