Effects of D‑Ala2, D‑Leu5‑Enkephalin pre‑ and post‑conditioning in a rabbit model of spinal cord ischemia and reperfusion injury

Abstract

It has recently been revealed that during the aorta-clamped period, D-Ala2, D-Leu5-Enkephalin (DADLE) infusion can protect the spinal cord against ischemia and reperfusion (I/R) injury. However, the protective effects of DADLE administration prior to ischemia or at the time of early reperfusion have not yet been investigated. Drug pre- or post-conditioning can serve as a more valuable clinical strategy. Therefore, the present study was designed to investigate the neuroprotective effect of DADLE infusion at different time intervals in order to determine the optimum time point for ischemic spinal cord protection. A total of 40 New Zealand white rabbits were randomly divided into 5 groups: Sham-operated (Sham), normal saline pre-conditioning (NS), DADLE per-conditioning (Dper), DADLE pre-conditioning (Dpre) and DADLE post-conditioning (Dpost). All animals were subjected to spinal cord ischemia for 30 min followed by 48 h reperfusion. Hind limb motor functions were assessed according to the Tarlov criterion when the animals regained consciousness, 6, 24 and 48 h after reperfusion. Histological analysis and the number of viable α-motor neurons were also used to assess the extent of spinal cord injury. Compared with the NS group, the Tarlov scores and the number of normal neurons were significantly higher in the Dper group (P<0.05), which were consistent with the results of a previous study. In addition, the paraplegia rate and loss of normal motor neurons were lower in the DADLE per- and post-conditioning groups compared with the DADLE pre-conditioning; however, these were not statistically significant. DADLE 0.05 mg/kg administration at three time points all mitigated normal motor neuron injury in the anterior horn and decreased the paraplegia rates in rabbits. The therapeutic benefits appeared best in the post-conditioning group with DADLE, and worst in the pre-conditioning group.

DADLE promotes autophagic flux and depresses necroptosis by inhibiting cytosolic phospholipase A2 mediated lysosomal membrane permeabilization after spinal cord injury

“…DADLE is a synthetic opioid peptide that functions by interacting with DOR. In the past, researchers have studied the pharmacological function of DADLE in brain ischaemia-reperfusion injury, oxygen-glucose deprivation (OGD) and spinal cord ischaemia and reperfusion injury [51,53]. This evidence indicates that DOR activation by DADLE may exert a neuroprotective role after neural injury.…”