The Neuroprotective Benefits of Central Adenosine Receptor Stimulation in a Soman Nerve Agent Rat Model
Technical rept. Sep 2012-Mar 2013
ARMY MEDICAL RESEARCH INST OF CHEMICAL DEFENSE ABERDEEN PROVING GROUND MD
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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.
- Anatomy and Physiology
- Organic Chemistry
- Chemical, Biological and Radiological Warfare