Abstracts

Rationale: Not all patients develop epilepsy and co-morbidities such as depression and cognitive deficits after a brain insult, suggesting that some individual may be predisposed or vulnerable. We make the hypothesis that past stressful events may render some individuals vulnerable for the development of epilepsy and co-morbidities. We wish to identify predictive biomarkers of the vulnerability state, and ways to reverse such vulnerability. We have already demonstrated that social defeat (SD) produced 2 populations of animals: 50% become vulnerable to epilepsy, depression and co-morbidities. After status epilepticus (SE), this vulnerable population displays accelerated epileptogenesis, depression and cognitive deficits. Low serum BDNF levels identify this vulnerable population after SD, but before SE. Treatment with a BDNF mimetic after SD, but before SE, abolishes the vulnerability (Becker et al., Ann Neurol 2015). Here, we tested whether vulnerability could be reversed after SE, and we investigated EEG biomarkers predictive of a vulnerability state. Methods: Animals were exposed or not to social defeat, and one month later to kainic acid induced status epilepticus or vehicle. Serum BDNF levels, and spatial and non-spatial memory were assessed at different time points. The depression-like profile was assessed using the Porsolt test, anhedonia, corticosterone levels and adrenal gland weight. We performed 24/7 wireless EEG recordings. The antioxydant Tempol was applied subcutaneously with a minipump during 4 days after SE. Results: We find that the future vulnerable population can already be identified based on their EEG properties before SD. The predictive value is as good as serum BDNF levels measured after SD. Tempol treatment after SE did not affect epileptogenesis in a strong way, but abolished the expression of a depression-like profile and cognitive deficits in the vulnerable population. Conclusions: It is therefore possible to identify a vulnerable population based on EEG features (even before the major stressful events that will render some individuals vulnerable) and serum BDNF levels (after the stressful events). The vulnerability to depression and co-morbidities can be reversed either before or after the brain insult triggering epileptogenesis. Although the treatment does not prevent the occurrence of seizures, preventing co-morbidities constitute a major improvement. Funding: Fondation pour la Recherche sur le Cerveau (FRC)