Department of Pharmacology, Ningxia Medical University, 1160 Shengli Street, Yinchuan, Ningxia Hui Autonomous Region, 750004, People's Republic of China.
Key Laboratory of Hui Ethnic Medicine Modernization, Ministry of Education, Ningxia Medical University, Yinchuan, Ningxia Hui Autonomous Region, 750004, People's Republic of China.
Neurochem Res. 2017 Nov;42(11):3186-3198. doi: 10.1007/s11064-017-2356-z. Epub 2017 Jul 28.
Neonatal hypoxic-ischemic brain damage (HIBD) is one of the leading causes of neonatal mortality and permanent neurological disability worldwide and the effective treatment strategies are not yet available. It has been demonstrated that Chitosan oligosaccharide (COS) exerts protective effect in vitro ischemic brain injury. However, no information is available on possible effects of COS on neonatal HIBD. To investigate the hypothesis of the potential neuroprotective effect of COS on the brain injury due to HIBD, 7-day-old Sprague-Dawley rats were treated with left carotid artery ligation followed by exposure to 8% oxygen (balanced with nitrogen) for 2.5 h at 37 °C. After COS treatment, the cerebral damage was measured by behavior tasks, 2,3,5-triphenyltetrazolium chloride(TTC), Hematoxyline-Eosin(HE), Nissl and Fluoro-Jade B(FJB)staining. In addition, the oxidative stress were assayed with ipsilateral hemisphere homogenates. Immunofluorescence staining were used to examine the activation of the astrocyte and microglia. Expression of inflammatory-related proteins were analyzed by western-blot analysis. In this study we found that administration of COS ameliorated early neurological reflex behavior, significantly reduce brain infarct volume and attenuated neuronal cell injury and degeneration. Furthermore, COS markedly decreased the level of MDA, lactic acid and increased SOD, GSH-Px and T-AOC. COS attenuated hypoxic-ischemic induced up-regulation of expressions of interleukin-1β (IL-1β), tumor necrosis factor alpha (TNF-α), meanwhile it dramatically increased the interleukin-10 (IL-10). These results suggest that COS exerts neuroprotection on hypoxic-ischemic brain damage in neonatal rats, it implies COS might be a potential therapeutic for the treatment of HIBD.
新生儿缺氧缺血性脑损伤（HIBD）是全球新生儿死亡和永久性神经功能障碍的主要原因之一，目前尚无有效的治疗策略。壳聚糖寡糖（COS）已被证明在体外缺血性脑损伤中具有保护作用。然而，目前尚无关于 COS 对新生儿 HIBD 可能影响的信息。为了研究 COS 对 HIBD 脑损伤的潜在神经保护作用的假设，将 7 日龄 Sprague-Dawley 大鼠用左侧颈总动脉结扎，然后在 37°C 下用 8%氧气（与氮气平衡）暴露 2.5 小时。COS 处理后，通过行为任务、2,3,5-三苯基氯化四氮唑（TTC）、苏木精-伊红（HE）、尼氏和氟代-Jade B（FJB）染色测量脑损伤。此外，用对侧半球匀浆测定氧化应激。免疫荧光染色用于检测星形胶质细胞和小胶质细胞的激活。通过 Western-blot 分析分析炎症相关蛋白的表达。在这项研究中，我们发现 COS 给药改善了早期神经反射行为，显著减少了脑梗死体积，并减轻了神经元细胞损伤和变性。此外，COS 显著降低了 MDA、乳酸的水平，增加了 SOD、GSH-Px 和 T-AOC。COS 减轻了缺氧缺血诱导的白细胞介素-1β（IL-1β）、肿瘤坏死因子-α（TNF-α）表达上调，同时显著增加了白细胞介素-10（IL-10）。这些结果表明，COS 对新生大鼠缺氧缺血性脑损伤具有神经保护作用，这意味着 COS 可能是治疗 HIBD 的潜在治疗方法。
