Neuroprotective effects of curcumin against rats with focal cerebral ischemia-reperfusion injury

Xu,Lu; Ding,Ling; Su,Yuanqi; Shao,Ruyue; Liu,Jie; Huang,Yan

doi:10.3892/ijmm.2019.4094

Neuroprotective effects of curcumin against rats with focal cerebral ischemia-reperfusion injury

Authors:
- Lu Xu
- Ling Ding
- Yuanqi Su
- Ruyue Shao
- Jie Liu
- Yan Huang
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Affiliations: School of Pharmacy, Chongqing Medical and Pharmaceutical College, Chongqing 401331, P.R. China, Pharmacy Department, The Central Hospital of Jiangjin, Chongqing 402260, P.R. China, Scientific Research and Teaching Department, Chongqing Traditional Chinese Medicine Hospital, Chongqing 400021, P.R. China
Published online on: February 11, 2019 https://doi.org/10.3892/ijmm.2019.4094
Pages: 1879-1887

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Abstract

The aim of the present study was to investigate the protective effects of curcumin and its effect on the methyl ethyl ketone/extracellular signal regulated kinase/cAMP‑response element binding protein (MEK/ERK/CREB) pathway. The study was conducted in vivo and in vitro as follows: In vivo: Focal cerebral ischemia‑reperfusion (IR) models of rats were made with the plug‑line method. Adult male Sprague‑Dawley rats were divided into four groups: Sham operation control group, IR and curcumin‑treatment groups (100 mg/kg and IC, 300 mg/kg). The effects of curcumin on neurological deficit scores, brain water content and infarct volumes were identified. Transmission electron microscope was utilized to observe morphological changes of hippocampal neurons; hematoxylin and eosin staining was used to observe morphological changes of brain tissue; and the terminal deoxynucleotidyl transferase (TdT)‑mediated dUTP nick end labeling method detected neurons apoptosis of hippocampal CA1. Finally, western blot analysis detected the expression of phosphorylated (p)‑MEK, p‑ERK, p‑CREB, B‑cell lymphoma‑2 (Bcl‑2) and Bcl‑2 associated X protein (Bax). In vitro: An oxygen‑glucose deprivation/reoxygenation method was used on primary cultured astrocytes to make cerebral ischemia‑reperfusion models in vitro. Astrocytes were randomly divided into five groups: Normoxia, oxygen‑glucose deprivation/reoxygenation (OGD/Reoxy), OGD/Reoxy + curcumin (5, 10, 20 µmol/l). The cell viability and toxicity were assessed by MTT and lactate dehydrogenase release assay, and levels of p‑MEK, p‑ERK and p‑CREB proteins were analyzed by the western blotting method. Curcumin was demonstrated to improve nerve damage symptoms and infarct volume, reduce brain water content, relieve neuronal apoptosis and also increase the expression of p‑MEK, p‑ERK, p‑CREB, Bcl‑2 and reduce Bax levels in vivo and in vitro. In conclusion curcumin can mitigate focal cerebral ischemia‑reperfusion injuries and this effect may be carried out through the MEK/ERK/CREB pathway.

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