Osteopontin attenuates inflammation via JAK2/STAT1 pathway in hyperglycemic rats after intracerebral hemorrhage
Gong L, Manaenko A, Fan R, Huang L, Enkhjargal B, Mcbride DW, Ding Y, Tang J, Xiao X, Zhang JH (2018)
Publication Type: Journal article
Publication year: 2018
Journal
Book Volume: 138
Pages Range: 160-169
DOI: 10.1016/j.neuropharm.2018.06.009
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.
Involved external institutions
Loma Linda University (LLU)
United States (USA) (US)
Zunyi Medical University
China (CN)
Chongqing Medical University
China (CN)
United States (USA) (US)
Zunyi Medical University
China (CN)
Chongqing Medical University
China (CN)
How to cite
APA:
Gong, L., Manaenko, A., Fan, R., Huang, L., Enkhjargal, B., Mcbride, D.W.,... Zhang, J.H. (2018). Osteopontin attenuates inflammation via JAK2/STAT1 pathway in hyperglycemic rats after intracerebral hemorrhage. Neuropharmacology, 138, 160-169. https://dx.doi.org/10.1016/j.neuropharm.2018.06.009
MLA:
Gong, Lei, et al. "Osteopontin attenuates inflammation via JAK2/STAT1 pathway in hyperglycemic rats after intracerebral hemorrhage." Neuropharmacology 138 (2018): 160-169.
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