Department of Pharmacology, Ningxia Medical University, Yinchuan, Ningxia Hui Autonomous Region 750004, People's Republic of China.
Ningxia Key Laboratory of Craniocerebral Diseases of Ningxia Hui Autonomous Region, Ningxia Medical University, Yinchuan, Ningxia Hui Autonomous Region 750004, People's Republic of China.
Biomed Pharmacother. 2019 Oct;118:109196. doi: 10.1016/j.biopha.2019.109196. Epub 2019 Jul 13.
Neonatal hypoxic-ischemic brain damage (HIBD) is a leading cause of death and perpetual neurological dysfunction in neonates. Vanillin (Van), a natural phenolic compound with neuroprotective properties, exerts neuroprotection on a gerbil model of global ischemia by inhibiting oxidative damage. This study aimed to explore the potential neuroprotective roles of Van in neonatal rats suffering from hypoxic-ischemic (HI). An HI model of 7-day-old SD rats was induced by left carotid artery ligation followed by exposure to 8% oxygen (balanced with nitrogen) for 2.5 h at 37 °C. At 48 h after intraperitoneal injection with Van (20, 40, and 80 mg/kg) or saline, neurobehavioral function, cerebral infract volume, brain water content, and histomorphological changes were performed to evaluate brain injury. Transmission electron microscopy and immunoglobulin G (IgG) staining were conducted to evaluate the integrity of the blood-brain barrier (BBB). The levels of oxidative stress and tight junction proteins, as well as the activities of matrix metalloproteinases (MMPs), were also determined in the ipsilateral hemisphere. Results showed that Van post-treatment significantly ameliorated early neurobehavioral deficits, decreased infarct volume and brain edema, as well as attenuated histopathologic injury and IgG extravasation. Furthermore, Van markedly increased the activities of endogenous antioxidant enzymes and decreased malondialdehyde content. Meanwhile, the activation of MMP-2 and MMP-9 induced by HI was partially blocked by Van. Finally, Van obviously increased the expression of ZO-1, Occludin, and Claudin-5 compared with the HI group. Collectively, Van can provide neuroprotective effects against neonatal HIBD possibly by attenuating oxidative damage and preserving BBB integrity.
新生儿缺氧缺血性脑损伤（HIBD）是导致新生儿死亡和永久性神经功能障碍的主要原因。香草醛（Van）是一种具有神经保护作用的天然酚类化合物，通过抑制氧化损伤对沙鼠全脑缺血模型发挥神经保护作用。本研究旨在探讨 Van 对缺氧缺血（HI）新生大鼠的潜在神经保护作用。通过结扎左侧颈总动脉，然后在 37°C 下暴露于 8%氧气（与氮气平衡）2.5 h 来诱导 7 日龄 SD 大鼠 HI 模型。在腹腔注射 Van（20、40 和 80 mg/kg）或生理盐水后 48 h，进行神经行为功能、脑梗死体积、脑水含量和组织形态学变化，以评估脑损伤。透射电子显微镜和免疫球蛋白 G（IgG）染色用于评估血脑屏障（BBB）的完整性。还在对侧半球测定氧化应激和紧密连接蛋白的水平以及基质金属蛋白酶（MMPs）的活性。结果显示，Van 后处理可显著改善早期神经行为缺陷，减少梗死体积和脑水肿，减轻组织病理学损伤和 IgG 漏出。此外，Van 明显增加内源性抗氧化酶的活性并降低丙二醛含量。同时，Van 部分阻断了 HI 诱导的 MMP-2 和 MMP-9 的激活。最后，与 HI 组相比，Van 明显增加了 ZO-1、Occludin 和 Claudin-5 的表达。总之，Van 可通过减轻氧化损伤和保护 BBB 完整性对新生 HIBD 提供神经保护作用。
