Accession Number : ADA465923


Title :   Efficacy of 2-APB (2-Aminoethyldiphenylborate) in Rescuing Neurons After Soman-Induced Brain Injury


Corporate Author : ARMY MEDICAL RESEARCH INST OF CHEMICAL DEFENSE ABERDEEN PROVING GROUND MD


Personal Author(s) : Ballough, Gerald P ; Kan, Robert K ; Nicholson, James D ; Fath, Denise M ; Tompkins, Christina P ; Filbert, Margaret G


Full Text : http://www.dtic.mil/dtic/tr/fulltext/u2/a465923.pdf


Report Date : Aug 2005


Pagination or Media Count : 18


Abstract : Soman produces seizures and seizure-related brain damage (SRBD). It is well known that termination of seizures using anticonvulsant drug therapy is the most effective means of preventing soman-induced SRBD. However, soman-induced seizures become refractive to anticonvulsant therapy within 40 minutes after their onset and the development of status epilepticus. Medical care for some battlefield casualties will likely be delayed beyond the therapeutic window of opportunity to terminate soman-induced seizures. Thus, there is a need for adjunct drug therapy that is neuroprotective when administered more than 40 minutes following soman exposure. Numerous evidence supports a pivotal role of sustained elevations in intracellular calcium (i.e., delayed calcium overload) in the development of brain damage resulting from seizures and status epilepticus. In addition, recent reports indicate that a sizable calcium influx occurs through transient receptor potential (TRP) channels, and this influx can be blocked by 2-aminoethyl diphenylborinate (2-APB; also called 2-aminoethoxy diphenylbroane and, misleadingly, 2-aminoethoxy diphenylborate). This study examined the possible neuroprotective effectiveness of 2-APB against soman-induced SRBD. Our results indicate that 2-APB (5.0 - 22.5 mg/kg in DMSO) was unable to ameliorate somaninduced SRBD. Moreover, we provide evidence that the DMSO vehicle (0.5 - 1.0 ml/kg) augmented temporal lobe lesions by soman.


Descriptors :   *EXPOSURE(PHYSIOLOGY) , *GD AGENT , *BRAIN DAMAGE , *CONVULSIVE DISORDERS , *NECROSIS , NERVE CELLS , DRUGS , ANTICONVULSANTS , EPILEPSY , NERVE AGENTS


Subject Categories : Medicine and Medical Research
      Chemical, Biological and Radiological Warfare


Distribution Statement : APPROVED FOR PUBLIC RELEASE