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Treatment with Manganese Porphyrin, MnTnBuOE-2-PyP5+, Suppressed the Activation of Macrophages in a Mouse Intracerebral Hemorrhage

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机构: [1]Department of Anesthesiology, Duke University Medical Center, Durham, NC 27710, USA. [2]Department of Anesthesiology, The 4th Hospital of Hebei Medical University, Shijiazhuang 050011, China. [3]Pharmacokinetics and Pharmacodynamics Core, Duke Cancer Institute, Durham, NC 27710, USA. [4]School of Forensic Medicine, Shanxi Medical University, Jinzhong 030600, China. [5]Department of Medicine, Duke University Medical Center, Durham, NC 27710, USA.
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关键词: manganese porphyrin MnTnBuOE-2-PyP5+ ischemic stroke hemorrhagic transformation neurologic outcome mouse macrophage ferroptosis BMX-001

摘要:
Background: Manganese porphyrin, MnTnBuOE-2-PyP5+ (BMX-001), improves neurologic deficits in experimental ischemic stroke and has the potential to serve as an adjunct with thrombolysis or thrombectomy in stroke patients. In 10-30% of stroke patients following thrombolysis, the hemorrhagic transformation, associated with iron release, occurs. This study aimed to examine the neurologic outcome following the BMX-001 treatment in a mouse intracerebral hemorrhage (ICH) model with relevance to prospective ischemic stroke clinical trials. Methods: Twenty C57Bl6 mice were randomly assigned to groups after surgery and received vehicle or BMX-001 treatment immediately following stereotaxic left striatum collagenase injection. Post-ICH body weight, the Corner test, neurological deficit score, and Rotarod test were examined. Six sham surgery mice serve as a control group. At 72 h, the brain histological evaluation was performed, including hemorrhage size, Prussian blue staining, and the activation of macrophages. Data were collected by a researcher who was blind to groups. Results: No significant difference in body weight, neurological deficits, and hemorrhage size was found between groups. However, BMX-001 reduced the number of macrophages in the hemorrhagic area (48 ± 10 in vehicle, 33 ± 8 in BMX-001, p = 0.008) and the number of cells stained with Prussian blue-an indicator of iron released during hemorrhage (65 ± 22 in vehicle and 41 ± 15 in BMX-001, p = 0.027). Conclusions: The results support the safe use of BMX-001 in stroke patients in combination with thrombolysis or thrombectomy and, moreover, indicate the beneficial anti-inflammatory effect of BMX-001, alike to that previously reported in stroke studies of analogous, similarly redox-active, Mn porphyrins.

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出版当年[2025]版:
大类 | 3 区 医学
小类 | 2 区 药学 3 区 药物化学
最新[2025]版:
大类 | 3 区 医学
小类 | 2 区 药学 3 区 药物化学
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出版当年[2024]版:
Q1 CHEMISTRY, MEDICINAL Q1 PHARMACOLOGY & PHARMACY
最新[2024]版:
Q1 CHEMISTRY, MEDICINAL Q1 PHARMACOLOGY & PHARMACY

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第一作者机构: [1]Department of Anesthesiology, Duke University Medical Center, Durham, NC 27710, USA. [2]Department of Anesthesiology, The 4th Hospital of Hebei Medical University, Shijiazhuang 050011, China.
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