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1.
Arq. neuropsiquiatr ; 66(4): 853-860, dez. 2008. ilus, graf
Artículo en Inglés | LILACS | ID: lil-500568

RESUMEN

Neurogenesis in the dentate gyrus (DG) has attracted attention since abnormal supragranular mossy fiber sprouting occurs in the same region, in temporal lobe epilepsy. Thus, we submitted developing rats to pilocarpine-induced status epilepticus (SE) to study the relationship between neurogenesis and mossy fiber sprouting. Groups were submitted to SE at: I-P9, II-P7, P8 and P9, III-P17 e IV-P21. Neurogenesis was quantified using BrdU protocol and confirmed through double staining, using neuronal pentraxin. Other animals were monitored by video system until P120 and their brain was studied (Timm and Nissl staining). The neurogenesis at P17 (p=0.007) and P21 (p=0.006) were increased. However, only P21 group showed recurrent seizures and the mossy fiber sprouting in the same region, during adult life, while P17 did not. Thus, our results suggest that neurogenesis is not related to mossy fiber sprouting neither to recurrent spontaneous seizures in pilocarpine model.


A neurogênese no giro dentado tem atraído atenção já que ela ocorre na mesma região do hipocampo que o brotamento das fibras musgosas, na epilepsia do lobo temporal. Assim, submetemos ratos em desenvolvimento ao status epilepticus induzido (SE) por pilocarpine. Grupos foram submetidos em I-P9, II-P7, P8, P9; III-P17 e IV-P21. A neurogênese foi observada usando o protocolo do BrdU e confirmada por dupla marcação com pentraxina neuronal. Outros animais foram monitorados até P120 e seus cérebros analisados (Nissl e Timm). A neurogênese nos grupos P17 (p=0,007) e P21 (p=0,006) aumentaram. Entretanto, o P21 apresentou crises espontâneas e brotamento de fibras musgosas, na mesma região onde ocorreu a neurogênese, enquanto o grupo P17 apresentou somente aumento na neurogênese. Assim, nossos resultados sugerem que o fenômeno da neurogênese não está relacionado com o brotamento de fibras musgosas nem com o aparecimento de crises espontâneas e recorrentes no modelo da pilocarpina.


Asunto(s)
Animales , Ratas , Giro Dentado/fisiopatología , Neurogénesis/fisiología , Estado Epiléptico/fisiopatología , Proliferación Celular/efectos de los fármacos , Giro Dentado/efectos de los fármacos , Giro Dentado/embriología , Inmunohistoquímica , Fibras Musgosas del Hipocampo/efectos de los fármacos , Fibras Musgosas del Hipocampo/embriología , Fibras Musgosas del Hipocampo/fisiopatología , Plasticidad Neuronal , Pilocarpina , Ratas Sprague-Dawley , Estado Epiléptico/inducido químicamente
2.
Braz. j. med. biol. res ; 41(5): 403-410, May 2008. ilus
Artículo en Inglés | LILACS | ID: lil-484433

RESUMEN

Intrahippocampal administration of kainic acid (KA) induces synaptic release of neurotrophins, mainly brain-derived neurotrophic factor, which contributes to the acute neuronal excitation produced by the toxin. Two protein tyrosine kinase inhibitors, herbimycin A and K252a, were administered intracerebroventricularly, in a single dose, to attenuate neurotrophin signaling during the acute effects of KA, and their role in epileptogenesis was evaluated in adult, male Wistar rats weighing 250-300 g. The latency for the first Racine stage V seizure was 90 ± 8 min in saline controls (N = 4) which increased to 369 ± 71 and 322 ± 63 min in animals receiving herbimycin A (1.74 nmol, N = 4) and K252a (10 pmol, N = 4), respectively. Behavioral alterations were accompanied by diminished duration of EEG paroxysms in herbimycin A- and K252a-treated animals. Notwithstanding the reduction in seizure severity, cell death (60-90 percent of cell loss in KA-treated animals) in limbic regions was unchanged by herbimycin A and K252a. However, aberrant mossy fiber sprouting was significantly reduced in the ipsilateral dorsal hippocampus of K252a-treated animals. In this model of temporal lobe epilepsy, both protein kinase inhibitors diminished the acute epileptic activity triggered by KA and the ensuing morphological alterations in the dentate gyrus without diminishing cell loss. Our current data indicating that K252a, but not herbimycin, has an influence over KA-induced mossy fiber sprouting further suggest that protein tyrosine kinase receptors are not the only factors which control this plasticity. Further experiments are necessary to elucidate the exact signaling systems associated with this K252a effect.


Asunto(s)
Animales , Masculino , Ratas , Benzoquinonas/farmacología , Carbazoles/farmacología , Epilepsia del Lóbulo Temporal/fisiopatología , Alcaloides Indólicos/farmacología , Ácido Kaínico/antagonistas & inhibidores , Lactamas Macrocíclicas/farmacología , Fibras Musgosas del Hipocampo/efectos de los fármacos , Proteínas Tirosina Quinasas/antagonistas & inhibidores , Análisis de Varianza , Muerte Celular/efectos de los fármacos , Muerte Celular/fisiología , Electroencefalografía , Inhibidores Enzimáticos/farmacología , Epilepsia del Lóbulo Temporal/inducido químicamente , Epilepsia del Lóbulo Temporal/patología , Agonistas de Aminoácidos Excitadores/farmacología , Ácido Kaínico/farmacología , Sistema Límbico/citología , Sistema Límbico/efectos de los fármacos , Fibras Musgosas del Hipocampo/patología , Fibras Musgosas del Hipocampo/fisiopatología , Factores de Crecimiento Nervioso , Ratas Wistar , Estadísticas no Paramétricas , Convulsiones/fisiopatología
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