Chen S T, Chuang J I
Department of Anatomy, College of Medicine, National Cheng Kung University, Tainan, Taiwan, Republic of China.
Exp Brain Res. 1999 Jan;124(2):241-7. doi: 10.1007/s002210050619.
The anti-excitotoxic efficacy of the pineal hormone melatonin was investigated in kainate-injured brains of rats. Kainate (a glutamate-receptor agonist, 2.5 nmol in 1 microl) was directly injected to unilateral striatum. Melatonin (10 mg/kg) was administrated intraperitoneally 1 h before and 1, 3, and 5 h after intrastriatal kainate injection in adult Sprague-Dawley rats. Three days after kainate injection, a significant neuronal damage was found, as determined by Nissl staining and the TUNEL method, not only in the injected striatum, but also in the ipsilateral neighboring cortex. The kainate-induced cortical apoptotic neuronal death was significantly attenuated by treatment with melatonin compared with the vehicle control group. However, no detectable changes were observed in the contralateral side of the brain in either vehicle- or melatonin-treated rats. Moreover, the biochemical results indicated that kainate can indeed induce oxidative stress, such as a decrease in the content of total glutathione (GSH), oxidized glutathione (GSSG), and an increase in the ratio of GSSG/GSH in the striatum and cortex compared with the contralateral brain regions. In the kainate-injected striatum, melatonin did not reduce the oxidative stress, but in the neighborhood of injected area-cortex, kainate-induced oxidative stress was significantly reduced by melatonin. Enhancement of glutathione-peroxidase activity was induced by intrastriatal kainate injection, not only in the cortical area of control and melatonin-treated rats, but also in striatum of control rats. However, a large elevation was found in the melatonin-treated cortex. Taking the morphological and biochemical data together, the present results suggest that melatonin functions as an antioxidant by upregulating the glutathione antioxidative defense system, thereby reducing neuronal death caused by excitotoxicity and preventing the kainate-induced damage from spreading to adjacent brain regions.
在大鼠的红藻氨酸损伤脑内研究了松果体激素褪黑素的抗兴奋毒性功效。将红藻氨酸（一种谷氨酸受体激动剂，1微升含2.5纳摩尔）直接注射到单侧纹状体。在成年Sprague-Dawley大鼠纹状体内注射红藻氨酸前1小时以及注射后1、3和5小时，腹腔注射褪黑素（10毫克/千克）。红藻氨酸注射三天后，通过尼氏染色和TUNEL法确定，不仅在注射的纹状体内，而且在同侧相邻皮质中都发现了明显的神经元损伤。与溶剂对照组相比，褪黑素治疗可显著减轻红藻氨酸诱导的皮质凋亡性神经元死亡。然而，在溶剂或褪黑素治疗的大鼠脑的对侧均未观察到可检测到的变化。此外，生化结果表明，与对侧脑区相比，红藻氨酸确实可诱导氧化应激，如纹状体和皮质中总谷胱甘肽（GSH）、氧化型谷胱甘肽（GSSG）含量降低以及GSSG/GSH比值升高。在注射红藻氨酸的纹状体内，褪黑素并未降低氧化应激，但在注射区域附近的皮质中，褪黑素可显著降低红藻氨酸诱导的氧化应激。纹状体内注射红藻氨酸不仅在对照和褪黑素治疗大鼠的皮质区域，而且在对照大鼠的纹状体内均可诱导谷胱甘肽过氧化物酶活性增强。然而，在褪黑素治疗的皮质中发现了大幅升高。综合形态学和生化数据，目前的结果表明，褪黑素通过上调谷胱甘肽抗氧化防御系统发挥抗氧化剂的作用，从而减少兴奋毒性引起的神经元死亡，并防止红藻氨酸诱导的损伤扩散到相邻脑区。
