Osteopontin attenuates inflammation via JAK2/STAT1 pathway in hyperglycemic rats after intracerebral hemorrhage. (August 2018)

• Record Type: Journal Article
• Authors: Gong, Lei; Manaenko, Anatol; Fan, Ruiming; Huang, Lei; Enkhjargal, Budbazar; McBride, DevinW.; Ding, Yan; Tang, Jiping; Xiao, Xiaoqiu; Zhang, John H.
• Is Part Of: Neuropharmacology. Volume 138(2018)
• Page Start: 160
• Page End: 169
• Publication Date: 2018-08
• Subjects: ICH -- Hyperglycemia -- Osteopontin -- Inflammation -- Brain edema; Neuropsychopharmacology -- Periodicals; Autonomic Agents -- Periodicals; Neuropsychopharmacologie -- Périodiques; Neuropsychopharmacology; Periodicals; Electronic journals; 615.78
• DOI: 10.1016/j.neuropharm.2018.06.009
• Languages: English
• ISSNs: 0028-3908

Abstract

Abstract: 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-β1 receptor and a JAK2 agonist, Coumermycin A1 (C-A1), were used for detailed investigation of the molecular pathway. The administration of OPN (3 μg) significantly improved neurobehavior and increased expression of OPN and integrin-β1 receptor in the brain followed with decrease of neutrophil infiltration, JAK2, STAT1, TNF-a, IL-1b, 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-β1 siRNA and C-A1. 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-β1 induced inhibition of JAK2/STAT1 pathway. Highlights: Effect of intranasal administration of rOPN explored after hyperglycemic ICH. rOPN attenuated inflammation and brain edema after hyperglycemic ICH. The effects of rOPN mediated by integrin-β1 dependent inhibition of JAK2/STAT1 pathway.