M Current-Based Therapies for Nerve Agent Seizures
Abstract
This is a proposal to develop novel, mechanism-based therapies for the treatment of organophosphate (OP) nerve agent-induced seizures. We proposed to study the effects of organophosphates anmuscarinic agonists on glutamatergic transmission, and on intrinsic excitability of principal hippocampal neurons test the hypothesis that cholinergic stimulation enhances excitatory synaptic transmission and increases and excitability (Aims 1 & 2). We have completed experiments 1.1-1.4 and 2.1-2.2 as proposed for years 1 &2 of this study and experimental results supported the hypothesis. A manuscript describing these results is now published online: M-type potassium channels modulate Schaffer-collateral CA glutamatergic synaptic transmission. J Physiol. 2012 doi: 10.1113/jphysiol.2012.235820. Third goal was to test whether drugs that open M channels wouterminate status epilepticus induced by an organophosphate and cholinergic agonist (Li/Pilocarpine). Two model of organophasphate-induced seizures were characterized and published: Characterization of status epilepticus induced by two organophosphates in rats. Epilepsy Res. http://dx.doi.org/10.1016/j.eplepsyres.2012.04.014. Experiments reveal M channel opener flupirtine terminates refractory status epilepticus in two models.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 2012
- Accession Number
- ADA574529
Entities
People
- Jaideep Kapur
- Jian L. Sun
- Marko Todorovic
- Terry Zhang
Organizations
- University of Virginia