Carbon monoxide-releasing molecule-3 protects against ischemic stroke by suppressing neuroinflammation and alleviating blood-brain barrier disruption
Year: 2018
Type: article
Abstract: BACKGROUND: At low levels, carbon monoxide (CO) has been shown to have beneficial effects on multiple organs and tissues through its potential anti-inflammatory, anti-apoptotic, and anti-proliferative properties. However, the effect of CO-releasing molecule (CORM)-3, a water-soluble CORM, on ischemic stroke and its mechanism of action are still unclear. METHODS: We investigated the role of CORM-3 in the mouse model of transient middle cerebral artery occlusion (tMCAO). CORM-3 or saline was administered to mice by retro-orbital injection at the time of reperfusion after 1-h tMCAO or at 1 h after sham surgery. We assessed infarct volume and brain water content at 24 and 72 h after ischemia, blood-brain barrier permeability at 6 and 72 h after ischemia, and neurologic deficits on days 1, 3, 7, and 14. RESULTS: Among mice that underwent tMCAO, those that received CORM-3 had significantly smaller infarct volume and greater expression of neuronal nuclear antigen (NeuN) and microtubule-associated protein 2 than did saline-treated mice. CORM-3-treated mice had significantly fewer activated microglia in the peri-infarction zone than did control mice and exhibited downregulated expression of ionized calcium-binding adapter molecule (Iba)-1, tumor necrosis factor-α, and interleukin 1β. CORM-3-treated mice had significantly lower brain water content and enhanced neurologic outcomes on days 3, 7, and 14 post-tMCAO. Lastly, CORM-3 treatment reduced Evans blue leakage; increased expression of platelet-derived growth factor receptor-β, tight junction protein ZO-1, and matrix protein laminin; and decreased protein level of matrix metalloproteinase-9. CONCLUSION: CORM-3 treatment at the time of reperfusion reduces ischemia-reperfusion-induced brain injury by suppressing neuroinflammation and alleviating blood-brain barrier disruption. Our data suggest that CORM-3 may provide an effective therapy for ischemic stroke.
Source: Journal of Neuroinflammation
Authors: Jianping Wang, Di Zhang, Xiaojie Fu, Lie Yu, Zhengfang Lu, Yufeng Gao, Xianliang Liu, Jiang Man, Sijia Li, Nan Li, Xuemei Chen, Michael Hong, Qingwu Yang, Jian Wang
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $4,090
Funders: Foundation for the National Institutes of Health, American Heart Association, Johns Hopkins University, National Natural Science Foundation of China, National Institutes of Health, Department of Anesthesiology and Critical Care Medicine, Johns Hopkins Medicine, National Institute of Neurological Disorders and Stroke, National Center for Complementary and Integrative Health
Awards: Neuroprotective effect of flavanol (-) epicatechin after intracerebral hemorrhage, G1495211646, G1542342083, G1926553762, Development of Novel Functional Markers for TBI Using Molecular MRI, G3082555802, G350871793, G4609162072, Inhibition of ferroptosis after intracerebral hemorrhage, PGE2 EP1 and EP3 receptors as therapeutic targets in intracerebral hemorrhage, Microglia/macrophage polarization after intracerebral hemorrhage, Depression after Intracerebral Hemorrhage: Role of Nrf2, G7503399571, G7677002597, 20-HETE and hemorrhagic brain injury, G8386269553
OpenAlex ID: W2808916825