Evaluation of the anticonvulsant and neuroprotective effect of intracerebral administration of growth hormone in rats / Evaluación del efecto anticonvulsivante y neuroprotector de la administración intracerebral de la hormona de crecimiento en ratas

Introduction The growth hormone (GH) has been reported as a crucial neuronal survival factor in the hippocampus against insults of diverse nature. Status epilepticus (SE) is a prolonged seizure that produces extensive neuronal cell death. The goal of this study was to evaluate the effect of intracerebroventricular administration of GH on seizure severity and SE-induced hippocampal neurodegeneration. Methodology Adult male rats were implanted with a guide cannula in the left ventricle and different amounts of GH (70, 120 or 220 ng/3 μl) were microinjected for 5 days; artificial cerebrospinal fluid was used as the vehicle. Seizures were induced by the lithium–pilocarpine model (3 mEq/kg LiCl and 30 mg/kg pilocarpine hydrochloride) one day after the last GH administration. Neuronal injury was assessed by Fluoro-Jade B (F-JB) staining. Results Rats injected with 120 ng of GH did not had SE after 30 mg/kg pilocarpine, they required a higher number of pilocarpine injections to develop SE than the rats pretreated with the vehicle, 70 ng or 220 ng GH. Prefrontal and parietal cortex EEG recordings confirmed that latency to generalized seizures and SE was also significantly higher in the 120 ng group when compared with all the experimental groups. FJ-B positive cells were detected in the hippocampus after SE in all rats, and no significant differences in the number of F-JB cells in the CA1 area and the hilus was observed between experimental groups. Conclusion Our results indicate that, although GH has an anticonvulsive effect in the lithium–pilocarpine model of SE, it does not exert hippocampal neuroprotection after SE. (AU)

Introducción La hormona de crecimiento (HC) es un factor que favorece la supervivencia neuronal en el hipocampo ante agresiones de diversa naturaleza. El status epilepticus (SE) es un tipo de crisis epiléptica de larga duración que produce muerte neuronal. El objetivo de este estudio fue evaluar el efecto de la administración intracerebroventricular de HC en la severidad de las convulsiones y la neurodegeneración hipocampal debida al SE. Metodología A ratas macho adultas se les implantó una cánula guía en el ventrículo lateral izquierdo y se les microinyectaron diferentes cantidades de HC (70, 120 o 220 ng/3 μl) durante 5 días; como vehículo se inyectó líquido cefalorraquídeo artificial. Las convulsiones se generaron con el modelo de litio-pilocarpina (3 mEq/kg LiCl y 30 mg/kg clorhidrato pilocarpina) un día después de la última inyección de HC. La neurodegeneración se identificó con la tinción de Fluoro-Jade B (F-JB). Resultados Las ratas a las que se les inyectaron 120 ng de HC requirieron 2 o 3 inyecciones de pilocarpina para desarrollar SE, en comparación con el resto de los grupos experimentales que requirieron solo una aplicación del convulsivante. Los registros EEG de la corteza prefrontal y parietal confirmaron que la latencia a las crisis generalizadas y al SE fue mayor en dicho grupo experimental. Todas las ratas con SE presentaron células positivas al FJ-B en el área CA1 e hilus del hipocampo, y no se identificaron diferencias entre los tratamientos. Conclusión Nuestros resultados muestran que, aunque la HC tiene un efecto anticonvulsivante, una vez que se ha desarrollado el SE no promueve neuroprotección en el hipocampo. (AU)

Hyperthermia aggravates status epilepticus-induced epileptogenesis and neuronal loss in immature rats.

This study tightly controlled seizure duration and severity during status epilepticus (SE) in postnatal day 10 (P10) rats, in order to isolate hyperthermia as the main variable and to study its consequences. Body temperature was maintained at 39 ± 1 °C in hyperthermic SE rats (HT+SE) or at 35 ± 1 °C in normothermic SE animals (NT+SE) during 30 min of SE, which was induced by lithium-pilocarpine (3 mEq/kg, 60 mg/kg) and terminated by diazepam and cooling to NT. All video/EEG measures of SE severity were similar between HT+SE and NT+SE pups. At 24h, neuronal injury was present in the amygdala in the HT+SE group only, and was far more severe in the hippocampus in HT+SE than NT+SE pups. Separate groups of animals were monitored four months later for spontaneous recurrent seizures (SRS). Only HT+SE animals developed convulsive SRS. Both HT+SE and NT+SE animals developed electrographic SRS (83% vs. 55%), but SRS frequency and severity were higher in hyperthermic animals (12.5 ± 3.5 vs. 4.2 ± 2.0 SRS/day). The density of hilar neurons was lower, thickness of the amygdala and perirhinal cortex was reduced, and lateral ventricles were enlarged in HT+SE over NT+SE littermates and HT/NT controls. In this model, hyperthermia greatly increased the epileptogenicity of SE and its neuropathological sequelae.