Department of Emergency Medicine, CHA University School of Medicine, 59 Yatap-Ro, Bundang-Gu, Seongnam 13496, Korea.
Department of Neurology, CHA University School of Medicine, 59 Yatap-Ro, Bundang-Gu, Seongnam 13496, Korea.
Int J Mol Sci. 2018 Nov 21;19(11):3679. doi: 10.3390/ijms19113679.
Several studies have demonstrated the beneficial effect of mesenchymal stem cells (MSCs) on intracerebral hemorrhage (ICH). Enhancement of the therapeutic efficacy of MSCs in ICH is necessary, considering the diseases high association with mortality and morbidity. Various preconditioning methods to enhance the beneficial properties of MSCs have been introduced. We suggested apocynin, a well-known nicotinamide adenine dinucleotide phosphate (NADPH) oxidase inhibitor, as a novel preconditioning regimen to enhance the therapeutic efficacy of MSCs in ICH. Rat ICH models were made using bacterial collagenase. 24 h after ICH induction, the rats were randomly divided into apocynin-preconditioned MSC-treated (Apo-MSC), naïve MSC-treated and control groups. Hematoma volume, brain edema, and degenerating neuron count were compared at 48 h after the ICH induction. The expression of tight junction proteins (occludin, zona occludens [ZO]-1) were also compared. Hematoma size, hemispheric enlargement and degenerating neuron count were significantly lower in the Apo-MSC group than in the naïve MSC group ( = 0.004, 0.013 and 0.043, respectively), while the expression of occludin was higher ( = 0.024). Apocynin treatment enhances the therapeutic efficacy of MSCs in ICH in the acute stage, through the improvement of the beneficial properties of MSCs, such as neuroprotection and the reinforcement of endovascular integrity of cerebral vasculature.
已有多项研究证实间充质干细胞（MSCs）对脑出血（ICH）具有有益作用。鉴于ICH 与高死亡率和高发病率密切相关，有必要增强 MSCs 的治疗效果。已经引入了各种预处理方法来增强 MSCs 的有益特性。我们建议使用一种众所周知的烟酰胺腺嘌呤二核苷酸磷酸（NADPH）氧化酶抑制剂——apocynin，作为一种新的预处理方案来增强 MSCs 在 ICH 中的治疗效果。使用细菌胶原酶建立大鼠 ICH 模型。ICH 诱导后 24 h，将大鼠随机分为 apocynin 预处理 MSC 治疗组（Apo-MSC）、未处理 MSC 治疗组和对照组。ICH 诱导后 48 h 比较血肿体积、脑水肿和变性神经元计数。还比较了紧密连接蛋白（occludin、zonula occludens [ZO]-1）的表达。与未处理 MSC 组相比，Apo-MSC 组的血肿体积、半球肿胀和变性神经元计数明显降低（=0.004、0.013 和 0.043），而 occludin 的表达更高（=0.024）。apocynin 治疗通过增强 MSCs 的神经保护和脑血管内皮完整性等有益特性，增强了 MSCs 在 ICH 急性期的治疗效果。
