Accession Number : ADA275955


Title :   Mechanisms and Treatment of OP-Induced Seizures and Neuropathology


Descriptive Note : Midterm rept. 30 Jun 1991-29 Jun 1993


Corporate Author : CINCINNATI UNIV OH COLL OF MEDICINE


Personal Author(s) : Shipley, Michael T ; Ennis, M ; El-Etri, M ; Zimmer, L ; Jiang, M


Full Text : https://apps.dtic.mil/dtic/tr/fulltext/u2/a275955.pdf


Report Date : 18 Aug 1993


Pagination or Media Count : 154


Abstract : This report summarizes studies on the mechanisms and treatment of soman-induced seizures and neuropathology. Major goals of this work are to identify the first sites exhibiting soman-induced hyperactivity and neuropathology, and to determine if neurotransmitters other than acetylcholine (ACh) are altered by soman. Markers for c-fos and reactive astrocytes pinpointed sites of seizures and neuropathology, and neurochemistry quantified neurotransmitter levels. Piriform cortex (PC) and the noradrenergic (NE) nucleus locus coeruleus (LC) first exhibited c-fos and reactive astrocytes after soman. Seizures, c-fos and reactive astrocytes in PC were also produced by stimulation of endogenous ACh inputs to PC. Soman caused increased LC neuronal activity, producing sustained NE release leading to depletion in convulsive but not nonconvulsive rats. As NE is proconvulsant in several seizure models, we hypothesize that soman-induced NE release plays a critical role in seizure induction and/or maintenance. This work indicates that increased ACh and NE play important roles in soman-induced seizures, and suggests new therapeutic approaches involving NE antagonists. Since many NE antagonists are used clinically, their combination with ACh antagonists could provide an improved, rapidly deployed postexposure protective regimen. Soman, Acetylcholine, Acetylcholinesterase, Piriform cortex, Norepinephrine, Locus coeruleus, Seizures, Convulsions.


Descriptors :   *NEUROCHEMISTRY , *NEUROTRANSMITTERS , MAINTENANCE , INPUT , DEPLETION , NEURAL NETS , BRAIN , MODELS , RATS , PROTEINS , SITES , RELEASE , POISONING , NOREPINEPHRINE , MARKERS , WORK , ANATOMY , RECREATION , ACETYLCHOLINESTERASE , ORGANOPHOSPHATES , CEREBRAL CORTEX , ACETYLCHOLINE , LOCUS , APPROACH , ASTROCYTES , OLFACTORY NERVE


Subject Categories : Anatomy and Physiology
      Medicine and Medical Research


Distribution Statement : APPROVED FOR PUBLIC RELEASE