RESUMEN
ß-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.
Asunto(s)
Antibacterianos/administración & dosificación , Ceftriaxona/administración & dosificación , Convulsivantes/farmacología , Glaucoma/fisiopatología , Fármacos Neuroprotectores/administración & dosificación , Convulsiones/prevención & control , Tetrazoles/farmacología , Enfermedad Aguda , Animales , Conducta Animal/efectos de los fármacos , Masculino , Ratones , Ratas , Ratas WistarRESUMEN
Glutamate is involved in excitotoxic mechanisms by interacting with different receptors. Such interactions result in neuronal death associated with several neurodegenerative disorders of the central nervous system (CNS). The aim of this work was to study the time course of changes in the expression of GluR1 and GluR2 subunits of glutamate amino-acid-3-hydroxy-5-methyl-isoxazol-4-propionic acid (AMPA) receptors in rat hippocampus induced by NMDA intrahippocampal injection. Rats were submitted to stereotaxic surgery for NMDA or saline (control) microinjection into dorsal hippocampus and the parameters were evaluated 24 h, 1, 2, and 4 weeks after injection. The extension and efficacy of the NMDA-induced injury were evaluated by Morris water maze (MWM) behavioral test and Nissl staining. The expression of GluR1 and GluR2 receptors, glial fibrillary acidic protein (GFAP), and neuronal marker (NeuN) was analyzed by immunohistochemistry. It was observed the impairment of learning and memory functions, loss of neuronal cells, and glial proliferation in CA1 area of NMDA compared with control groups, confirming the injury efficacy. In addition, NMDA injection induced distinct changes in GluR1 and GluR2 expression over the time. In conclusion, such changes may be related to the complex mechanism triggered in response to NMDA injection resulting in a local injury and in the activation of neuronal plasticity.