ABSTRACT
INTRODUCCIÓN: La epilepsia del lóbulo temporal se desarrolla como consecuencia de insultos cerebrales como trauma, infartos, infección o convulsiones. Los circuitos neuronales del lóbulo temporal, incluyendo al hipocampo, se reorganizan generando redes hiperexcitables, el foco epiléptico, proceso denominado epileptogénesis; en cambio, la corteza cerebral es más resistente a la reorganización. La epileptogénesis en el hipocampo está mediada en parte por óxido nítrico, sintetizado por la óxido nítrico sintasa neuronal y por la neurotrofina BDNF, cuyo receptor es TrkB. Estas proteínas están localizadas en las sinapsis excitadoras y podrían estar implicadas en la sensibilidad diferencial entre el hipocampo y corteza cerebral a la epileptogénesis. OBJETIVO: Lograr un acercamiento a los mecanismos que participan en la sensibilidad diferencial a la epileptogénesis entre el hipocampo y la corteza, después de convulsiones. MATERIAL Y MÉTODO: Se indujeron convulsiones en ratas mediante inyección de kainato. Se obtuvieron membranas sinápticas reselladas (sinaptosomas) de corteza e hipocampo. En ellas, se cuantificó la co-localización de óxido nítrico sintasa neuronal, TrkB y un marcador de sinapsis excitadoras (Prosap2) mediante técnicas inmunohistoquímicas. Los resultados expresados como por ciento promedio +/- error estándar se sometieron a prueba de t-student. RESULTADOS: TrkB y óxido nítrico sintasa neuronal aumentaron de 20,6 +/- 3,5 por ciento a 35,7 +/- 2,6 por ciento (p = 0,0008) y de 32,4 +/- 3,8 por ciento a 51,5 +/- 3,5 por ciento (p = 0,0003), respectivamente, en sinaptosomas excitadores hipocampales después de convulsiones. En sinaptosomas excitadoras de cerebro corteza no se observaron cambios significativos. DISCUSIÓN: óxido nítrico sintasa neuronal y TrkB se asocian a sinapsis excitadoras hipocampales después de convulsiones, pudiendo contribuir así a la epileptogénesis. La cerebrocorteza es resistente a esta reorganización molecular.
INTRODUCTION: Temporal lobe epilepsy develops as a consequence of brain insults such as trauma, stroke, infection, or seizures. The temporal lobe circuit, including the hippocampus, reorganizes generating hyper-excitable networks and, therefore, the epileptic focus, process called epileptogenesis. Where as, the cerebral cortex is more resistant to the reorganization. Temporal lobe epileptogenesis is mediated partly by neuronal nitric oxide synthase and the neurotrophin BDNF with its receptor TrkB. These proteins are localized at excitatory synapses and might be involved in the differential sensitivity of the hippocampus and cerebral cortex to epileptogenesis. OBJECTIVE: Getting closer to mechanisms involved in epileptogenesis differential sensitivity between the hippocampus and cortex after seizures. MATERIAL AND METHOD: Seizures were induced in rats by injection of kainic acid. Resealed synaptic membranes (synaptosomes) were obtained from cortex and hippocampus. Then the co-localization of neuronal nitric oxide synthase, TrkB and a marker of excitatory synapses (Prosap2/Shank3) was quantified by immunohistochemistry. The results were expressed as mean +/- standard error and subjected to t-student test. RESULTS: TrkB and neuronal nitric oxide synthase increased from 20.6 +/- 3.5 percent to 35.7 +/- 2.6 percent (p = 0.0008) and from 32.4 +/- 3.8 percent to 51.5 +/- 3.5 percent (p = 0.0003), respectively in excitatory hippocampal synaptosomes after seizures. In excitatory cerebrocortical synaptosomes no significant changes were observed. DISCUSSION: neuronal nitric oxide synthase and TrkB associate to excitatory hippocampal synapses after seizures, thereby probably contributing to epileptogenesis. The cerebral cortex is resistant to this molecular reorganization.
Subject(s)
Male , Animals , Rats , Cerebral Cortex/metabolism , Epilepsy/metabolism , Hippocampus/metabolism , Nitric Oxide Synthase/metabolism , Receptor, trkB , Kainic Acid/administration & dosage , Carrier Proteins , Epilepsy/chemically induced , Brain-Derived Neurotrophic Factor/metabolism , Temporal Lobe/metabolism , Rats, Sprague-Dawley , SynaptosomesABSTRACT
In order to localize groups of neurons commanding the defense reaction, a subtoxic dose (66 pmol) of kainic acid was microinjected into the medial hypothalamus of the rat. After drug treatment, the animals were placed inside a shuttle-box for 15 min and the number of midline crossings, rearings and forward leaps was recorded. Autonomic changes such as occurrence of micturition and defectation were also measured. Injection of kainic acid significantly increased locomotion, rearing and micturition, indicating that the medial hypothalamus of the rat contains perikarya/dendrites of neurons integrating the defense reaction
Subject(s)
Rats , Animals , Male , Escape Reaction/drug effects , Hypothalamus, Middle/drug effects , Kainic Acid/pharmacology , Neurons/drug effects , Kainic Acid/administration & dosage , Locomotion/drug effects , Microinjections , Rats, Inbred StrainsABSTRACT
Kainic acid (KA) is a powerful convulsant and neurotoxic agent. In the present paper the acute and long term effects of intrahippocampal KA administration on estrous cycle and on serum concentrations of progesterone were studied in adult female rats. Following KA injection, 3 distinct periods were observed: 1) acute period (24-48 h), 2) silent period (21-30 days), and 3) chronic period, characterized by the appearance of spontaneous of spontaneous recurrent seizures (30-45 days). KA administration did not affect progesterone levels during the acute period. In contrast, during the sislent period, KA treated animals exhibited irregular estrous cycling and decreased progesterone levels. These results are of interest in view of a possible link between epileptic phenomena and hormone secretion