Cyclopentyl-adenosine decreases caspase-3 activity and LDH release following simulated ischemia in cerebellar granule neurons

Activation of adenosine A1 receptors in vivo or in vitro, prior to simulated ischemic insults have been demonstrated to be neuroprotective. Preconditioning with A1 receptor agonists, both in vivo and in vitro, has been shown to induce neuroprotective effects against necrosis even when administered 24–72 hours before ischemic insult. This thesis examined the neuroprotective effects of the selective A1 receptor agonist, N6-cyclopentyl-adenosine (CPA), against both apoptotic and necrotic cell death following simulated ischemia in cultured rat cerebellar granule neurons. Using antibodies directed towards neuronal nuclear protein and glial fibrillary acid protein, the purity of cerebellar granule cell cultures was found to be 98.6 ± 0.4%. This indicates that the results from these experiments were likely mediated by effects of the drugs and simulated ischemia on neurons and not astrocytes. To determine if the neuroprotection induced by CPA treatment was mediated by activation of A1 receptors, a concentration response curve for DPCPX was generated in the presence and absence of 1μM CPA. (Abstract shortened by UMI.).