Accession Number:

ADA465923

Title:

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

Descriptive Note:

Corporate Author:

ARMY MEDICAL RESEARCH INST OF CHEMICAL DEFENSE ABERDEEN PROVING GROUND MD

Report Date:

2005-08-01

Pagination or Media Count:

18.0

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 mgkg in DMSO was unable to ameliorate somaninduced SRBD. Moreover, we provide evidence that the DMSO vehicle 0.5 - 1.0 mlkg augmented temporal lobe lesions by soman.

Subject Categories:

  • Medicine and Medical Research
  • Chemical, Biological and Radiological Warfare

Distribution Statement:

APPROVED FOR PUBLIC RELEASE