Melatonin reduces experimental subarachnoid hemorrhage-induced oxidative brain damage and neurological symptoms
Melatonin reduces experimental subarachnoid hemorrhage-induced oxidative brain damage and neurological symptoms
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DOI：
10.1111/j.1600-079x.2009.00664.x
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发表时间：
2009-04-01
影响因子：
10.3
通讯作者：
Sener, Goksel
中科院分区：
文献类型：
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作者：
Ersahin, Mehmet;Toklu, Hale Z.;Sener, Goksel
氧化应激在包括蛛网膜下腔出血（SAH）在内的几种神经退行性疾病模型中具有不利影响。本研究在SAH大鼠模型中研究了褪黑素（一种强大的抗氧化剂）的神经保护作用。将雄性Wistar白化大鼠分为对照组、载药组和褪黑素组（10 mg/kg, ig）。SAH组。大鼠大池注射0.3 mL血液诱导SAH。SAH诱导48小时后，测量神经学检查评分，并将大鼠斩首。取脑组织标本进行血脑屏障（BBB）通透性、脑含水量、组织学检查或测定丙二醛（MDA）和谷胱甘肽（GSH）水平、髓过氧化物酶（MPO）和Na+-K+- atp酶活性。利用化学发光（CL）技术监测脑组织样品中活性氧的形成。在SAH诱导的第二天，SAH组的神经学检查评分升高，SAH引起脑GSH含量和Na+-K+- atp酶活性显著降低，同时CL、MDA水平和MPO活性显著升高。另一方面，褪黑激素治疗逆转了所有这些生化指标以及sah诱导的组织病理学改变，而褪黑激素治疗也逆转了脑含水量增加和血脑屏障受损。本研究提示，褪黑素可轻易穿过血脑屏障，减轻sah诱导的氧化应激，并通过保持血脑屏障的通透性和减少脑水肿发挥神经保护作用。
Oxidative stress has detrimental effects in several models of neurodegenerative diseases, including subarachnoid hemorrhage (SAH). This study investigated the putative neuroprotective effect of melatonin, a powerful antioxidant, in a rat model of SAH. Male Wistar albino rats were divided as control, vehicle-treated SAH, and melatonin-treated (10 mg/kg, i.p.) SAH groups. To induce SAH, 0.3 mL blood was injected into cisterna magna of rats. Forty-eight hours after SAH induction, neurological examination scores were measured and the rats were decapitated. Brain tissue samples were taken for blood-brain barrier (BBB) permeability, brain water content, histological examination, or determination of malondialdehyde (MDA) and glutathione (GSH) levels, myeloperoxidase (MPO), and Na+-K+-ATPase activities. Formation of reactive oxygen species in brain tissue samples was monitored by using a chemiluminescence (CL) technique. The neurological examination scores were increased in SAH groups on the second day of SAH induction and SAH caused a significant decrease in brain GSH content and Na+-K+-ATPase activity, which was accompanied with significant increases in CL, MDA levels, and MPO activity. On the other hand, melatonin treatment reversed all these biochemical indices as well as SAH-induced histopathological alterations, while increased brain water content and impaired BBB were also reversed by melatonin treatment. This study suggests that melatonin, which can easily cross BBB, alleviates SAH-induced oxidative stress and exerts neuroprotection by preserving BBB permeability and by reducing brain edema.