Dose-dependent neuroprotection of delta-opioid peptide [D-Ala2, D-Leu5] enkephalin on spinal cord ischemia-reperfusion injury by regional perfusion into the abdominal aorta in rabbits

Abstract

In our prior study, we showed that delta-opioid peptide [D-Ala(2), D-Leu(5)] enkephalin (DADLE), by regional perfusion into the abdominal aorta, could protect the spinal cord against ischemia-reperfusion (I/R) injury caused by aortic occlusion. However, the relative dose-response effects of DADLE still remain unclear. This study investigated whether DADLE has a dose-dependent efficiency on spinal cord I/R injury. New Zealand White rabbits were randomly divided into one of six groups: normal saline (NS; n= 8), DADLE (D) groups D0.0005 (n= 8), D0.005 (n= 8), D0.05 (n= 8), and D0.5mg/kg (n= 8), and a sham group (n= 6). In the NS and DADLE groups, spinal cord ischemia was induced by infrarenal aortic occlusion for 30minutes. During the occlusion, the same volume of NS or DADLE at the indicated doses was infused continuously through a catheter to the distally clamped abdominal aorta. Heart rate, blood pressure, and core temperature were monitored continuously to evaluate the potential adverse effects of DADLE. Neurologic behavioral function was assessed with the Tarlov scale system at 1, 6, 24, 48, and 72hours after reperfusion. Neuronal injury evaluation in the ventral horn of the gray matter was evaluated by counting the normal motor neurons at 72hours after reperfusion. The therapeutic benefits increased at the doses of DADLE from 0.0005 to 0.05mg/kg and decreased at 0.5mg/kg, whereas the hemodynamic parameter was suppressed temporarily at the dose of 0.5mg/kg. These data revealed that regional administration of DADLE through the abdominal aorta provided dose-dependent protection on spinal cord I/R in rabbits.