RESUMO
Several clinical and experimental reports suggest that low-dose irradiation of an established epileptic focus can reduce the occurrence of spontaneous seizures. Conversely, some recent reports suggest that under some conditions low-dose irradiation may have disinhibitory effects on seizure expression. Here, we have investigated mechanistic aspects of this phenomenon in the kindling model of epilepsy by applying focal irradiation at various points during kindling development. Rats were kindled to stage 5 by afterdischarge-threshold electrostimulation of the left amygdala. Treatment groups were irradiated using a collimated X-ray beam (18 MV) either prior to kindling, at kindling stage 3, or at kindling stage 5, by exposure of the left amygdala to a single-fraction central-axis dose of 25 Gy. Generalized seizure thresholds (GSTs) were subsequently assayed at weekly intervals for 10 weeks and at monthly intervals for an additional 3 months, along with the severity of the evoked seizures. Irradiation produced no significant effects on seizure threshold, but did produce persistent changes in seizure severity which varied as a function of the timing of irradiation. Relative to sham irradiated controls, the occurrence of stage 6 seizures was significantly increased by irradiation prior to kindling, but was unaffected by irradiation at kindling stage 3, and significantly reduced by irradiation at kindling stage 5. Quantitative immunohistochemical assays for neuron and astrocyte densities within the amygdala and hippocampus revealed only subtle changes in neuronal density within the dentate granule cell layer. These results are discussed in relation to mechanisms of seizure- and radiation-induced plasticity.
Assuntos
Tonsila do Cerebelo/efeitos da radiação , Epilepsia/radioterapia , Hipocampo/efeitos da radiação , Excitação Neurológica/efeitos da radiação , Vias Neurais/efeitos da radiação , Tonsila do Cerebelo/patologia , Tonsila do Cerebelo/fisiopatologia , Animais , Astrócitos/patologia , Astrócitos/efeitos da radiação , Biomarcadores/metabolismo , Contagem de Células , Proteínas de Ligação a DNA , Modelos Animais de Doenças , Progressão da Doença , Estimulação Elétrica , Epilepsia/fisiopatologia , Epilepsia/prevenção & controle , Proteína Glial Fibrilar Ácida/metabolismo , Hipocampo/patologia , Hipocampo/fisiopatologia , Excitação Neurológica/fisiologia , Masculino , Proteínas do Tecido Nervoso/metabolismo , Vias Neurais/patologia , Vias Neurais/fisiopatologia , Plasticidade Neuronal/fisiologia , Plasticidade Neuronal/efeitos da radiação , Neurônios/patologia , Neurônios/efeitos da radiação , Proteínas Nucleares/metabolismo , Doses de Radiação , Radiação Ionizante , Radioterapia/métodos , Ratos , Ratos Wistar , Fatores de Tempo , Resultado do TratamentoRESUMO
Low-dose radiosurgery is presently in use as a treatment modality for focal epilepsy, but the mechanisms underlying the associated changes in seizure expression are poorly understood. We investigated whether total and parvalbumin expressing (PV+) neuronal densities within the hippocampus and amygdala are affected by analogous focal irradiation in amygdala-kindled rats. Adult rats were kindled by electrical stimulation through 10 stage 5 seizures. The kindled amygdala was then focally irradiated at 18 or 25 Gy, and generalized seizure thresholds were subsequently monitored for approximately 6 months. Histological and immunohistochemical assays of total and PV+ neuronal densities were performed bilaterally throughout the hippocampus and within the basolateral amygdala. PV+ neuronal densities were unaffected by kindling or irradiation in these regions. Kindling selectively reduced neuronal densities in the dentate granule cell layer, and medial CA3 pyramidal cell layer. Irradiation at 25 Gy, but not at 18 Gy, prevented or reversed this kindling-associated reduction in density.
