Abstracts

Rationale: Currently the most important neuroprotective approach in case of status epilepticus (SE) is the early recognition and treatment. It has been shown in animal model that diazepam started 2 h, but not 3 h after SE, reduce dramatically the severity of hippocampal cell loss (Francois et al., 2006;Pitkanen et al., 2005). We also showed that inflammation increases the vulnerability of immature hippocampus to seizure-induced neuronal injury (Auvin et al., 2007). Here, we assess the role of inflammation in adult rats exposed to lithium pilocarpine model (LiPC). The level of cell injury after a protection obtained by benzodiazepine and the ability of Serum Neuron Specific Enolase (NSE)level to predict the level of injury were studied. Methods: Wistar rats were subjected to LiPC SE (administration of 3mEq/kg LiCl followed by the injection of pilocarpine (30 mg/kg) . All rats received 2.5mg/kg of diazepam i.p. 2 hours after the start of SE in order to decrease cell injury. Different amount of LPS (50, 100, 250 or 500 µg/kg) was given i.p. 2 h prior to the injection of pilocarpine according to the studied groups. 24h after the SE, animals were euthanized, boold samples were collected and brains processed for histological evaluation using hematoxylin-eosin and fluorojade B stainings. Serum NSE was mesured. Results: LPS increases cell injury following SE even when a protection was given by an early injection of diazepam, while LPS only does not induce cell injury. As previously described, the level of cell injury in CA-1 was very low in SE group treated by diazepam. The increase of the level of cell injury appears to be dependent of the amount of LPS given prior to the SE (Figure 1). LPS alone was able to increase the NSE. The NSE levels fail to predict the level of cell injury and the differences between the groups. The level of NSE was different between SE and LPS500+SE groups while the differences did not reach the significant for SE vs LPS50+SE (p=0.06), SE vs LPS100+SE (p=0.073) and SE vs LPS250+SE (p=0.06). Moreover, NSE did not permit to distinguish saline group vs SE group and LPS500 vs LPS500+SE groups (Figure 2). Conclusions: Our study showed that inflammation are an aggravating factor of cell injury following SE in mature rat brain even when diazepam is used to reduce cell injury. NSE is not a reliable biomarker to predict acute cell injury in setting of inflammation. We are currently investigating if we can identify a reliable biomarker using MRI studies.