Hemin‑mediated neuroglobin induction exerts neuroprotection following ischemic brain injury through PI3K/Akt signaling

Zhang,Bei; Ji,Xiuping; Zhang,Shijun; Ren,Huiyun; Wang,Minjuan; Guo,Changjiang; Li,Yajun

doi:10.3892/mmr.2013.1523

Hemin‑mediated neuroglobin induction exerts neuroprotection following ischemic brain injury through PI3K/Akt signaling

Authors:
- Bei Zhang
- Xiuping Ji
- Shijun Zhang
- Huiyun Ren
- Minjuan Wang
- Changjiang Guo
- Yajun Li
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Affiliations: Department of Neurology, Affiliated Hospital of Xi'an Medical University, Xi'an, Shaanxi 710077, P.R. China, Department of Traditional Medicine, Affiliated Hospital of Xi'an Medical University, Xi'an, Shaanxi 710077, P.R. China
Published online on: June 13, 2013 https://doi.org/10.3892/mmr.2013.1523
Pages: 681-685

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Abstract

The aim of the present study was to uncover the mechanism underlying the neuroprotection of Hemin‑mediated neuroglobin (Ngb) in an in vivo model of brain injury. Sixty healthy male Sprague-Dawley rats were randomly divided into 5 groups (n=12, each group): sham surgery, ischemia, Hemin, LY294002 (LY) and Hemin + LY. Focal cerebral ischemia was established by unilateral middle cerebral artery occlusion. Neurological function and cerebral infarction volume were evaluated 24 h following surgery. Expression of Ngb and Akt mRNA was detected by RT‑PCR, and the expression of Ngb protein and activation of the PI3K/Akt pathway were determined by western blot analysis. No visible damage in the brain and no neurological impairment in the sham surgery group were observed. When compared with the ischemia group, Hemin treatment induced the upregulation of Ngb and Akt mRNA, Ngb protein and phosphorylation of Akt (pAkt). Hemin treatment also improved neurological functions and reduced infarct volume. By contrast, LY treatment increased infarct volume, deteriorated neurological functions and significantly reduced expression of pAkt; however, Ngb mRNA and protein expression was unchanged. When compared with Hemin alone, a combination of Hemin and LY treatment induced more severe brain damage and markedly decreased the expression of pAkt. The results of the present study demonstrated that the PI3K/Akt signaling pathway, which is associated with cell survival, mediates the neuroprotective effects of Hemin‑induced Ngb following cerebral ischemia.

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