Neuroprotection From Op-Induced Seizures and Neuropathology.
Abstract
This report summarizes studies on the mechanisms and treatment of soman-induced seizures and neuropathology. Our previous contract work showed that piriform cortex (PC) is the earliest cortical are involved in soman-induced seizures. Work in our laboratory and others indicate that seizure activity is maintained by NMDA receptors (NRs). Recent studies have shown that NRs exhibit varying subunit composition and the specific subunit composition determines the functional properties of NRs. The diversity of NR subtypes poses a serious challenge to the development of specific pharmacological interventions to block soman induced seizures. Ultimately, protective strategies will benefit from a description of the NR makeup of PC neurons. Thus, characterization of the composition of NRs in PC, a major goal of this contract, is an important step in the understanding and treatment of soman-induced seizures. This report summarizes the results of experiments using reverse transcriptase-polymerase chain reaction (RT-PCR) techniques to compare the relative levels of NR subunits in the PC and other cortical regions. The comparative expressions of NR1, NR2A, NR2B, NR2C, NR2D and NR3 subunits were analyzed in the PC, entorhinal, visual and motor cortices, and the olfactory bulb. This analysis showed that NR2B was the most heavily expressed subunit in all of the brain regions examined. These results suggest that NR2B is an important component of the NRs while NR2C, NR2D and NR-L are not essential for activities of most NRs in the forebrain areas examined. Strategies aimed at blocking seizures may need to focus on selective antagonists to the NR2B subunit. This report also describes a novel, long variant of the NR3 subunit identified in this contract work.
Document Details
- Document Type
- Technical Report
- Publication Date
- Mar 01, 1999
- Accession Number
- ADA366659
Entities
People
- Micahel T. Shipley
Organizations
- University of Maryland, Baltimore