Banca de QUALIFICAÇÃO: CAROLINE PEREIRA DE ARAÚJO

Uma banca de QUALIFICAÇÃO de MESTRADO foi cadastrada pelo programa.
DISCENTE : CAROLINE PEREIRA DE ARAÚJO
DATA : 27/04/2018
HORA: 18:00
LOCAL: INSTITUTO DO CEREBRO
TÍTULO:

Evaluation of behavioral change after induction of status epilepticus for intrahippocampal administration of pilocarpine and kainic acid in mice.

PALAVRAS-CHAVES:

Temporal Lobe Epilepsy, comorbidity, pilocarpine, kainic acid, hippocampus, memory.

PÁGINAS: 96
GRANDE ÁREA: Ciências Biológicas
ÁREA: Fisiologia
RESUMO:

Temporal Lobe Epilepsy (TLE) is the most common form of focal epilepsy. The human condition can be modeled in animals by the systemic administration of pilocarpine (PILO) or kainic acid (KA). The experimental approach involves an initial insult (status epilepticus) resulting in wide-spread cell death, structural reorganization, chronic spontaneous seizures and, impaired performance in memory tasks and anhedonia. The identification of the anatomical substrates related to the cognitive impairments in those models is not entirely known, since systemic administration may lead to multiple epileptic foci. To minimize the impact of spatially distributed, numerous epileptic foci, on cognitive performance, we present a protocol in which the convulsant agent is administered directly in the target structure of interest (i.e., straight into the hippocampus). This approach has been used for KA in mice, but no systematic study has evaluated the effects of intrahippocampal administration of PILO. Here, we describe the acute and chronic behavioral effects of the intrahippocampal administration of PILO (4 doses: 70, 245, 400 e 700 µg, in 1 µL) in mice during isoflurane anesthesia. KA (20 mM, 50 nL) and saline (0.9 %) were used as positive and negative controls, respectively. The results show a correlation between the severity of the status epilepticus and the dose of PILO given. Interestingly, intrahippocampal PILO injection (N=60) did not elicit tonic seizures, as commonly observed after systemic administration which contributed to the low mortality rate of the model (4 out of 60 and 10 out of 11, respectively). In the chronic phase (1 month after status epilepticus), mice treated with high doses of PILO and KA presented spontaneous seizures. Behavioral tests revealed that animals of the PILO group had lower stereotyped ambulation (open field) and higher saccharin consumption when compared to the KA group. On the other hand, treatment with PILO, especially at high doses, impaired performance in object recognition and spatial memory tasks (Barnes maze). Together, these data demonstrate that intrahippocampal administration of PILO in mice results in spontaneous and recurrent seizures, in addition to moderate cognitive impairment (compatible with comorbidities observed in humans with TLE) and, low mortality. We conclude that the present model has face validity for human TLE, and may serve as an alternative to KA models (whose cost is high) and systemic administration of PILO (whose mortality is high).

MEMBROS DA BANCA:
Presidente - 1728817 - CLAUDIO MARCOS TEIXEIRA DE QUEIROZ
Interno - 1996111 - MARTIN PABLO CAMMAROTA
Interno - 1698305 - RODRIGO NEVES ROMCY PEREIRA