Banca de DEFESA: CAROLINE PEREIRA DE ARAÚJO

Uma banca de DEFESA de MESTRADO foi cadastrada pelo programa.
DISCENTE : CAROLINE PEREIRA DE ARAÚJO
DATA : 31/08/2018
HORA: 11:00
LOCAL: INSTITUTO DO CEREBRO
TÍTULO:
PALAVRAS-CHAVES:

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

PÁGINAS: 75
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 - SE) 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 described 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 SE and
the dose of PILO given (measured acutely by behavioral scores and indirectly through the evolution of weight). Interestingly, intrahippocampal PILO injection (N=62) did not elicit tonic seizures, as commonly observed after systemic administration which contributed to the low mortality rate of the model (4 out of 63 and 10 out of 11, respectively). In the chronic phase (1 month after SE), mice treated with high doses of PILO and KA presented spontaneous seizures. Behavioral tests revealed that epileptic animals (independent of the convulsive drug used) present higher stereotyped ambulation (in the open-field) than animals from the control group. In hippocampal-dependent memory tests, PILO treatment, especially at high doses, impaired performance in the object
recognition task, but not in the Barnes maze. Animals from the KA group presented impaired performance in all memory tests compared with the PILO group (high dose). Taken together, our results demonstrate that ihpc
administration of PILO in mice results in spontaneous and recurrent seizures, as well as moderate cognitive impairment (compatible with comorbidities observed in humans with TLE), and low mortality rate. We believe that the present model has face validity for human TLE, and may serve as an alternative to KA models (which are expensive) and to the route of administration (high mortality when PILO is administered systemically).

MEMBROS DA BANCA:
Presidente - 1728817 - CLAUDIO MARCOS TEIXEIRA DE QUEIROZ
Interno - 1996111 - MARTIN PABLO CAMMAROTA
Externo à Instituição - BEATRIZ DE OLIVEIRA MONTEIRO