Accession Number : ADA600940


Title :   The Neuroprotective Benefits of Central Adenosine Receptor Stimulation in a Soman Nerve Agent Rat Model


Descriptive Note : Technical rept. Sep 2012-Mar 2013


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


Personal Author(s) : Thomas, Thaddeus P ; Shih, Tsung-Ming A


Full Text : https://apps.dtic.mil/dtic/tr/fulltext/u2/a600940.pdf


Report Date : Apr 2014


Pagination or Media Count : 25


Abstract : The primary aim of this study was to investigate the role of central adenosine receptor (AR) stimulation in neuroprotection by directly injecting (6)-cyclopentyladenosine (CPA), an adenosine agonist specific to the A1 receptor subtype (A1R), into the brain intracerebroventricularly (ICV) in a soman seizure rat model. In addition to general A1R stimulation, we hypothesized that bilateral micro-injection of CPA into the cholinergic basal forebrain (BF) and of the adenosine A2AR agonist CGS21680 into the GABAergic ventrolateral pre-optic area (VLPO) could also suppress excitotoxic activity. The results from these studies demonstrated that centrally administered adenosine agonists are anti-seizure and neuroprotective. CPA-delivered ICV prevented seizure and convulsion in 100% of the animals. Moreover, neuropathological evaluation indicated that adenosine treatments reduced brain damage from severe to minimal. Inhibition of the BF via CPA and stimulation of the VLPO via CGS21680 had varied results. Some animals were protected by treatment; however, others displayed similar pathology to the control. Overall, these data suggest that stimulating central ARs could be an effective target for the next generation countermeasures for nerve agent intoxication.


Descriptors :   *ADENOSINE , *GD AGENT , *NEUROBIOLOGY , *RECEPTOR SITES(PHYSIOLOGY) , DOSAGE , NERVE AGENTS , NEUROBLASTOMA , RATS


Subject Categories : Biology
      Anatomy and Physiology
      Organic Chemistry
      Chemical, Biological and Radiological Warfare


Distribution Statement : APPROVED FOR PUBLIC RELEASE