机构:[a]Department of Neurology, Xuanwu Hospital, Capital Medical University, Beijing, China神经科系统神经内科首都医科大学宣武医院[b]Advanced Center of Stroke, Beijing Institute for Brain Disorders, Beijing, China[c]Department of China-America Institute of Neuroscience, Xuanwu Hospital, Capital Medical University, Beijing, China科技平台中美神经科学研究所首都医科大学宣武医院[d]Department of Neurology, Affiliated Hospital of Jiujiang University, Jiujiang, China[e]Department of Neurology, Jingdezhen First People’s Hospital, Jingdezhen, China[f]Department of Neurology, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai, China[g]Department of Neurosurgery, Wayne State University School of Medicine, Detroit, MI, USA[h]Department of Neurosurgery, Henry Ford Health System, Detroit, MI, USA
Background and purpose: Low-dose of carbon monoxide delivered by CO-releasing molecule-2 (CORM-2) had been confirmed having anti-inflammatory efficacy in some inflammatory diseases. Herein, we assessed the usefulness of CORM-2 in correcting intracerebral hemorrhage (ICH)-mediated inflammation. Methods: Healthy male Sprague Dawley (SD) rats randomly entered into four groups: sham-ICH, ICH, ICH+CORM-2, and ICH+ inactive carbon monoxide releasing molecule 2 (iCORM-2). ICH was induced by 50 mu l of autologous arterial blood injected in situ in the rat brain. Neuro-functions of the ICH rats were evaluated with Garcia 18 scores at the 6th, 24th , 48th hou, and the fifthh day post-ICH. And brain tissues surrounding the hematoma area were collected from all ICH rats and assayed with Western blot and immunofluoresence analysis. Results: Neuro-dysfunctions in ICH rats were very severe than those in ICH +CORM-2 rats. Compared to sham group, the levels of HO-1, IKK beta, NF-kappa B, and TNF-alpha in ICH group began to elevate at the 6th hour, and reached to peak at the 48th hour post-ICH, all p < 0.05. While in ICH +CORM-2 group, the expressions of IKK beta, NF-kappa B, and TNF-alpha were very weaker than that in ICH group at every time points mentioned above; however, this phenomenon was not reproduced in ICH + iCORM-2 group. HO-1 in ICH+CORM-2 group highlighted in perihematomal area with many activated microglia (Iba-1-positive cells) and co-expressed with TNF-alpha, all of which were diminished at the fifth day post-ICH. Conclusion: CORM-2 may attenuate ICH-mediated inflammation by inhibiting microglial activation, which may involve the IKK/NF-kappa B pathway.
基金:
This study was sponsored by the National Key R&D
Program of China [2017YFC1308401], the National
Natural Science Foundation [81371289, 81660209,
81760221], National Science & Technology Foundational
Resource Investigation Program of China [2018FY100900]
and the Social Science and Technology Development Fund of Shanghai Fengxian District Science and Technology
Commission [20191301].
第一作者机构:[a]Department of Neurology, Xuanwu Hospital, Capital Medical University, Beijing, China[b]Advanced Center of Stroke, Beijing Institute for Brain Disorders, Beijing, China[c]Department of China-America Institute of Neuroscience, Xuanwu Hospital, Capital Medical University, Beijing, China[d]Department of Neurology, Affiliated Hospital of Jiujiang University, Jiujiang, China
共同第一作者:
通讯作者:
通讯机构:[a]Department of Neurology, Xuanwu Hospital, Capital Medical University, Beijing, China[b]Advanced Center of Stroke, Beijing Institute for Brain Disorders, Beijing, China[c]Department of China-America Institute of Neuroscience, Xuanwu Hospital, Capital Medical University, Beijing, China[d]Department of Neurology, Affiliated Hospital of Jiujiang University, Jiujiang, China[*1]Xuanwu Hospital, Capital Medical University, Beijing 100053, China[*2]Affiliated Hospital of Jiujiang University, Jiujiang, Jiangxi 332000, China