Pediatric Susceptibility to Nerve Agent-Induced Seizures and Effectiveness of Anticonvulsant Treatments
Annual rept. 26 Sep 2012 25 Sep 2013
UTAH UNIV SALT LAKE CITY
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Organophosphate OP poisoning can result in status epilepticus SE, a medical emergency which can become pharmacoresistant if treatment is delayed. Little to no data exists on pediatric models of OP-induced SE, even though the immature brain is likely to respond differently to OPs, and the optimal therapies are also likely to differ from adults. Our aim is to identify novel drugs that block pharmacoresistant OP-induced SE in children. In the past year, we have provided USAMRICD investigators with the miniature telemetry devices and recording apparatus for recording from P7 and P14 rats. We have developed rat models for DPF exposure for ages P7, P14, P21, and P28. We have found that P7 and P14 rat pups have brief minutes seizure behavior in response to DFP, while P21 and P28 animals develop SE which is robust and lasts for several hours. We see extensive neuronal injury in P28 rats using Fluoro-Jade B as a marker. We have developed an electrographic profile for the EEG activity of DFP-treated P21 and P28 animals, and are working on profiles for P7 and P14 DFP-treated rat pups. We have begun characterizing the effects of midazolam on DFP-induced SE in P21 and P28 rat pups, and we find that midazolam ameliorates the SE triggered by the organophosphate.
- Medicine and Medical Research