Valproate sodium (VPA) is a traditional antiepileptic drug with a neuroprotective role in cerebrovascular disease. After intracerebral hemorrhage (ICH), mechanical compression by hematoma, neuroinflammation, oxidative stress, and cytotoxicity of hematoma lysates caused the destruction of the blood brain barrier (BBB). Targeting BBB is a major therapeutic method for patients with ICH. The purpose of the present study was to explore the role of VPA in preserving BBB integrity in the ICH model and investigate the underlying molecular mechanisms. One hundred and thirty-six adult male CD1 mice were randomly divided into five groups in the study. Mice subjected to ICH were administered intraperitoneally with VPA at 3, 24, and 48 h post-ICH, respectively. Neurobehavioral assessments, BBB permeability, Evans blue fluorescence, hematoma volume, and protein expression were evaluated. The administration of VPA reduced BBB permeability and improved the neurobehavior significantly post-ICH. VPA administration significantly decreased the expression of phosphorylated nuclear factor-kappa B (p-NFκB), matrix metalloproteinases 9 (MMP9), tumor necrosis factorα (TNFα), and interleukin-6 (IL-6), while it enhanced the expression of claudin 5 and occludin in the brain. In conclusion, VPA administration maintained the integrity of BBB after experimental ICH, thus reducing brain edema and improving the neurological outcomes. Therefore, VPA administration might be a new therapeutic method to protect BBB integrity for patients with ICH.

中文翻译：

---

丙戊酸钠可保护脑出血小鼠的血脑屏障完整性

丙戊酸钠（VPA）是一种传统的抗癫痫药，在脑血管疾病中具有神经保护作用。脑出血（ICH）后，血肿溶解物的机械性压迫，神经炎症，氧化应激和血肿溶解产物的细胞毒性导致血脑屏障（BBB）的破坏。靶向BBB是ICH患者的主要治疗方法。本研究的目的是探讨ICH模型中VPA在保持BBB完整性中的作用并研究潜在的分子机制。在研究中，将136只成年雄性CD1小鼠随机分为五组。在ICH后3、24和48 h分别对腹膜内给予VPA的小鼠进行VPA。神经行为评估，血脑屏障通透性，伊文思蓝荧光，血肿量，和蛋白质表达进行了评估。VPA的使用可降低ICH后的BBB通透性，并显着改善神经行为。VPA给药显着降低了磷酸化核因子-κB（p-NFκ B），基质金属蛋白酶9（MMP9），肿瘤坏死因子α（TNF α）和白细胞介素-6（IL-6），而它在大脑中增强紧密连接蛋白5和闭合蛋白的表达。总之，在实验性脑出血后，VPA给药可维持BBB的完整性，从而减少脑水肿并改善神经功能。因此，VPA给药可能是保护ICH患者BBB完整性的一种新的治疗方法。