Osteopontin attenuates inflammation via JAK2/STATI pathway in hyperglycemic rats after intracerebral hemorrhage

NEUROPHARMACOLOGY

卷:138

Article

Gong, Lei^1,2  Manaenko, Anatol³  Fan, Ruiming⁴  Huang, Lei²  Enkhjargal, Budbazar²  McBride, Devin W.²  Ding, Yan²  Tang, Jiping²  Xiao, Xiaoqiu¹  Zhang, John H.² 

[1] Chongqing Med Univ, Affiliated Hosp 1, Dept Obstet & Gynecol, Chongqing 400016, Peoples R China

[2] Loma Linda Univ, Sch Med, Dept Physiol & Pharmacol, Loma Linda, CA 92354 USA

[3] Univ Erlangen Nurnberg, Dept Neurol, Erlangen, Germany

[4] Zunyi Med Univ, Affiliated Hosp, Dept Cerebrovasc, Zunyi 563000, Guizhou, Peoples R China

关键词: ICH;    Hyperglycemia;    Osteopontin;    Inflammation;    Brain edema;   

DOI  :  10.1016/j.neuropharm.2018.06.009

来源: Elsevier

【 摘 要 】

Acute intracerebral hemorrhage (ICH) complicated by hyperglycemia is associated with aggravation of post-stroke inflammation, leading to exacerbation of brain edema and predicting poor neurological outcomes and higher mortality of patients. Osteopontin (OPN) is a neuroprotective glycoprotein, which is able to attenuate brain injury induced by hemorrhagic stroke. In the current study we investigated whether OPN will decrease the inflammatory post-ICH response as well as attenuate brain edema and neurological deficits in hyperglycemic rats. We employed a collagenase model of ICH on male Sprague-Dawley rats (n = 148) rats and 50% of Dextrose was injected intraperitoneally (i.p) 3 h after ICH (ICH + HG). Intranasal administration of recombinant OPN (rOPN) was performed 1 h after ICH. The development of brain injury was evaluated by brain water content (BWC) and neurological deficits, western blot and immunohistochemistry study. Small interfering ribonucleic acid (siRNA) for integrin-beta 1 receptor and a JAK2 agonist, Coumermycin Al (C-A1), were used for detailed investigation of the molecular pathway. The administration of OPN (3 mu g) significantly improved neurobehavior and increased expression of OPN and integrin-beta 1 receptor in the brain followed with decrease of neutrophil infiltration, JAK2, STATI, TNF-a, IL-lb, MMP-9 and brain edema in the ICH + HG + OPN rats compared with ICH + HG rats. The effects of OPN were reversed by the intervention of intergrin-beta 1 siRNA and C-Al. In conclusion, rOPN attenuated ICH-induced brain inflammation in hyperglycemic rats, leading to attenuation of brain edema and improving neurological functions. Effects of rOPN were mediated at least partly by integrin-beta 1 induced inhibition of JAK2/STAT1 pathway. (C) 2018 Elsevier Ltd. All rights reserved.

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