Patiño Paloma, Parada Esther, Farré-Alins Victor, Molz Simone, Cacabelos Ramón, Marco-Contelles José, López Manuela G, Tasca Carla I, Ramos Eva, Romero Alejandro, Egea Javier
Paediatric Unit, La Paz University Hospital, Paseo de la Castellana 261, 28046-Madrid, Spain.
Instituto de Investigación Sanitaria, Servicio de Farmacología Clínica, Hospital Universitario de la Princesa, Madrid, Spain; Instituto Teófilo Hernando and Department of Pharmacology, Universidad Autónoma de Madrid, C/Arzobispo Morcillo 4, 28029 Madrid, Spain.
Neurotoxicology. 2016 Dec;57:61-68. doi: 10.1016/j.neuro.2016.09.002. Epub 2016 Sep 9.
Therapeutic interventions on pathological processes involved in the ischemic cascade, such as oxidative stress, neuroinflammation, excitotoxicity and/or apoptosis, are of urgent need for stroke treatment. Melatonin regulates a large number of physiological actions and its beneficial properties have been reported. The aim of this study was to investigate whether melatonin mediates neuroprotection in rat hippocampal slices subjected to oxygen-glucose-deprivation (OGD) and glutamate excitotoxicity. Thus, we describe here that melatonin significantly reduced the amount of lactate dehydrogenase released in the OGD-treated slices, reverted neuronal injury caused by OGD-reoxygenation in CA1 and CA3 hippocampal regions, restored the reduction of GSH content of the hippocampal slices induced by OGD, and diminished the oxidative stress produced in the reoxygenation period. Furthermore, melatonin afforded maximum protection against glutamate-induced toxicity and reversed the glutamate released almost basal levels, at 10 and 30μM concentration, respectively. Consequently, we propose that melatonin might strongly and positively influence the outcome of brain ischemia/reperfusion.
针对缺血级联反应中涉及的病理过程，如氧化应激、神经炎症、兴奋性毒性和/或细胞凋亡进行治疗干预，对于中风治疗来说迫在眉睫。褪黑素调节大量生理活动，并且其有益特性已有报道。本研究的目的是调查褪黑素是否介导对经历氧糖剥夺（OGD）和谷氨酸兴奋性毒性的大鼠海马切片的神经保护作用。因此，我们在此描述，褪黑素显著减少了OGD处理切片中释放的乳酸脱氢酶量，逆转了OGD复氧在海马CA1和CA3区域引起的神经元损伤，恢复了OGD诱导的海马切片中谷胱甘肽含量的降低，并减少了复氧期产生的氧化应激。此外，褪黑素分别在10μM和30μM浓度下，对谷氨酸诱导的毒性提供了最大保护，并将谷氨酸释放量几乎逆转至基础水平。因此，我们认为褪黑素可能对脑缺血/再灌注的结果产生强烈且积极的影响。
