The Neuroprotective Benefits of Central Adenosine Receptor Stimulation in a Soman Nerve Agent Rat Model
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.
Document Details
- Document Type
- Technical Report
- Publication Date
- Apr 01, 2014
- Accession Number
- ADA600940
Entities
People
- Thaddeus P. Thomas
- Tsung-ming A. Shih
Organizations
- United States Army Medical Research Institute of Chemical Defense