Abstract
Background. The adenosine A 2A agonist ATL-146e ameliorates reperfusion inflammation, reducing subsequent paralysis and neuronal apoptosis after spinal cord ischemia. We hypothesized that neuroprotection with ATL-146e involves inducible neuronal adenosine A 2A receptors (A 2A-R) that are upregulated after ischemia. Methods. Eighteen rabbits underwent laparotomy, and 14 sustained spinal cord ischemia from cross-clamping the infrarenal aorta for 45 minutes. One group (ischemia-reperfusion [I/R] + ATL) received ATL-146e intravenously for 3 hours during spinal cord reperfusion. A second group (I/R) received equivolume intravenous saline solution for 3 hours and served as an ischemic control, and a third group (Sham) underwent sham laparotomy. At 48 hours, all subjects were assessed for motor impairment using the Tarlov scoring system (0 to 5). Lumbar spinal cord sections were immunolabeled for A 2A-R and graded in a blinded fashion using light microscopy. Results. There was a significant improvement in Tarlov scores in I/R + ATL animals compared with the I/R group. Sham-operated animals demonstrated no A 2A-R immunoreactivity. There was a dramatic increase in A 2A-R immunoreactivity in neurons of lumbar spinal cord sections from I/R compared with I/R + ATL and sham-operated animals. Conclusions. Reduction in paralysis in animals receiving ATL-146e correlates with the new finding of A 2A-R expression on lumbar spinal cord motor neurons after ischemia. Adenosine A 2A agonists may exert neuroprotective effects by binding to inducible neuronal A 2A-R that are upregulated during spinal cord reperfusion, and reduced in response to administration of an A 2A-R-specific agonist.
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