Neurobiology and Venoms Laboratory, Department of Biology, FFCLRP, University of São Paulo, São Paulo, Brazil.
Instituto de Neurociências e Comportamento de Ribeirão Preto-INeC, Ribeirão Preto, São Paulo, Brazil.
J Biochem Mol Toxicol. 2020 Nov;34(11):e22578. doi: 10.1002/jbt.22578. Epub 2020 Jul 15.
β-Lactam antibiotics such as ceftriaxone, are potent stimulators of the expression of l-glutamate transporter GLT-1 and may exert neuroprotective effects when chronically used in rats and mice. In this study, we used two animal models to test the neurological effect of subchronic treatment with ceftriaxone: experimental acute glaucoma in Wistar rats and induction of acute seizures with pentylenetetrazole in mice. We also assessed the performance of mice in the rotarod to calculate therapeutic indexes and exploratory activity in the open field. Our results showed that subchronic use of ceftriaxone was neuroprotective in both models, reducing injury in acute ischemia and ischemia/reperfusion in specific layers of retina and leading to a decrease in the seizure severity score. In behavioral experiments, we observed that ceftriaxone increased hyperactivity followed by a decrease in exploratory behavior in the open field, and there was no motor impairment in the rotarod test. We conclude that ceftriaxone may be useful as a tool in the development of new neuroprotective drugs targeting diseases which present a possible dysfunction in the balance of glutamatergic neurotransmission.
β-内酰胺类抗生素，如头孢曲松，是 l-谷氨酸转运体 GLT-1 表达的有效刺激物，在大鼠和小鼠中长期使用时可能具有神经保护作用。在这项研究中，我们使用了两种动物模型来测试头孢曲松亚慢性治疗的神经学效应：Wistar 大鼠的实验性急性青光眼和戊四氮诱导的急性惊厥，以及在旋转棒上评估小鼠的表现，以计算治疗指数和在开阔场中的探索性活动。我们的结果表明，头孢曲松在两种模型中均具有神经保护作用，可减轻急性缺血和特定视网膜层的缺血再灌注损伤，并降低惊厥严重程度评分。在行为实验中，我们观察到头孢曲松增加了过度活跃，随后在开阔场中减少了探索性行为，而在旋转棒测试中没有运动障碍。我们得出结论，头孢曲松可能是一种有用的工具，可用于开发针对谷氨酸能神经传递可能出现功能障碍的疾病的新型神经保护药物。
