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.临床科室麻醉科河北医科大学第四医院[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.
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.
基金:
This research was funded by the Department of Anesthesiology.
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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推荐引用方式(GB/T 7714):
Zhang Shasha,Cao Jie,Spasojevic Ivan,et al.Treatment with Manganese Porphyrin, MnTnBuOE-2-PyP5+, Suppressed the Activation of Macrophages in a Mouse Intracerebral Hemorrhage[J].Pharmaceuticals (Basel, Switzerland).2025,18(4):doi:10.3390/ph18040547.
APA:
Zhang Shasha,Cao Jie,Spasojevic Ivan,Treggiari Miriam&Sheng Huaxin.(2025).Treatment with Manganese Porphyrin, MnTnBuOE-2-PyP5+, Suppressed the Activation of Macrophages in a Mouse Intracerebral Hemorrhage.Pharmaceuticals (Basel, Switzerland),18,(4)
MLA:
Zhang Shasha,et al."Treatment with Manganese Porphyrin, MnTnBuOE-2-PyP5+, Suppressed the Activation of Macrophages in a Mouse Intracerebral Hemorrhage".Pharmaceuticals (Basel, Switzerland) 18..4(2025)