Zhang Shasha, Cao Jie, Spasojevic Ivan, Treggiari Miriam, Sheng Huaxin
Department of Anesthesiology, Duke University Medical Center, Durham, NC 27710, USA.
Department of Anesthesiology, The 4th Hospital of Hebei Medical University, Shijiazhuang 050011, China.
Pharmaceuticals (Basel). 2025 Apr 8;18(4):547. doi: 10.3390/ph18040547.
: Manganese porphyrin, MnTnBuOE-2-PyP (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. : 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. : 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, = 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, = 0.027). : 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.
锰卟啉MnTnBuOE-2-PyP(BMX-001)可改善实验性缺血性卒中的神经功能缺损,有潜力作为辅助治疗手段用于卒中患者的溶栓或取栓治疗。在接受溶栓治疗的卒中患者中,有10%至30%会发生与铁释放相关的出血性转化。本研究旨在通过小鼠脑出血(ICH)模型,研究BMX-001治疗后的神经功能转归,这与未来的缺血性卒中临床试验相关。:20只C57Bl6小鼠在手术后随机分组,在立体定向左侧纹状体注射胶原酶后立即接受赋形剂或BMX-001治疗。检测脑出血后体重、转角试验、神经功能缺损评分和转棒试验。6只假手术小鼠作为对照组。在72小时时,进行脑组织学评估,包括出血大小、普鲁士蓝染色和巨噬细胞活化情况。数据由对分组情况不知情的研究人员收集。:各组之间在体重、神经功能缺损和出血大小方面未发现显著差异。然而,BMX-001减少了出血区域的巨噬细胞数量(赋形剂组为48±10,BMX-001组为33±8,P = 0.008)以及普鲁士蓝染色细胞的数量(普鲁士蓝染色细胞数量是出血时释放铁的指标,赋形剂组为65±22,BMX-001组为41±15,P = 0.027)。:结果支持BMX-001与溶栓或取栓联合用于卒中患者的安全性,此外,表明BMX-001具有有益的抗炎作用,这与之前在类似的、具有类似氧化还原活性的锰卟啉卒中研究中所报道的作用相似。