Dose-dependent neuroprotection of delta-opioid peptide [D-Ala 2 , D-Leu 5 ] enkephalin on spinal cord ischemia-reperfusion injury by regional perfusion into the abdominal aorta in rabbits

Liu, Haitong; Chen, Binbin; Li, Shitong; Yao, Junyan

doi:10.1016/j.jvs.2014.11.074

Cited by 12 publications

(8 citation statements)

References 24 publications

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“…The median number of viable α-motor neurons at 48 h after reperfusion was 3.5 (range, 2–4) in the D per group, which was significantly higher than the median value of 0.5 (range, 0–1) in the NS group (corrected P=0.0060), but lower than the median value of 7 (range, 5.25–7) in the Sham group (corrected P=0.0018). The results of the Tarlov scores and histopathological examination of the spinal cords of the rabbits that received DADLE were consistent with a previous study (15).…”

Section: Resultssupporting

confidence: 91%

“…The model of 30 min aortic occlusion in rabbits was established, as previously described (15,17). Briefly, under general anesthesia, the femoral arteries of the rabbits were exposed.…”

Section: Methodsmentioning

confidence: 99%

“…A previous study has demonstrated that administration of 0.05 mg/kg DADLE by regional perfusion into the clamped aorta during the ischemic period, could induce neuroprotective efficacy against spinal cord I/R in rabbits (15). Whether an improved effect may be acquired when DADLE was delivered prior to ischemia onset or in the early reperfusion phase remains unclear.…”

Section: Introductionmentioning

confidence: 99%

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

Liu

et al. 2019

Mol Med Report

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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.

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Section: Resultssupporting

confidence: 91%

“…The model of 30 min aortic occlusion in rabbits was established, as previously described (15,17). Briefly, under general anesthesia, the femoral arteries of the rabbits were exposed.…”

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

Liu

et al. 2019

Mol Med Report

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“…Despite intensive efforts to develop new neuroprotective agents for experimental central nervous system ischemia models, most so far have failed to show clinical effects. Our previous studies showed that DADLE could attenuate spinal cord I/R injury during the ischemic period and the neuroprotective effect appeared most significant at a dose of 0.05 mg/kg (Liu et al, 2016 ). Antioxidative and antiapoptotic properties of DADLE were only reported in vitro experiments or in the model of cerebral I/R injury (Tsao et al, 1998 ; Hayashi et al, 2002 ).…”

Section: Discussionmentioning

confidence: 99%

“…The model of spinal cord ischemia was established as described previously (Liu et al, 2016 ). In brief, an incision was made in the right iliac region and the right femoral artery was exposed.…”

Section: Methodsmentioning

confidence: 99%

Antioxidative and Antiapoptotic Effects of Delta-Opioid Peptide [D-Ala2, D-Leu5] Enkephalin on Spinal Cord Ischemia-Reperfusion Injury in Rabbits

Liu

et al. 2017

Front. Neurosci.

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Background: In our previous study, we found that regional administration of delta-opioid peptide [D-Ala2, D-Leu5] enkephalin (DADLE) could provide dose-dependent protection on spinal cord ischemia-reperfusion (I/R) injury in rabbits. However, the relative protective molecular mechanisms underlying this neuroprotection remain unclear. The purpose of this study was to investigate whether DADLE provided the protection in spinal cord I/R injury through its antioxidant property by decreasing malondialdehyde (MDA) and nitric oxide (NO) levels and increasing glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD) levels and through its antiapoptotic capacity by inhibiting caspase-3 and p53 expression.Methods: The rabbits were divided into three groups. The animals in Group NS and Group DADLE were administered with normal saline (NS) or DADLE via aorta during 30 min of ischemia respectively, while the one in Group Sham received no intervention. During the period of reperfusion, the rabbit's blood samples were collected for enzyme-linked immunoabsorbent assay (ELISA) examinations of MDA, NO, GSH-Px and SOD. At 48 h after reperfusion, the lumbar spinal cords were harvested for immunohistochemical, real-time polymerase chain reaction (PCR) and western blot studies to detect the caspase-3 and p53 expressions.Results: The activities of serum MDA and NO showed significant reductions in the DADLE group as compared with the control group. By contrast, the levels of serum GSH-Px and SOD were significantly higher in the DADLE group than those in the NS group. In addition, caspase-3 and p53 expression were significantly increased in the NS group, while DADLE mitigated these changes.Conclusions: The protective effects of DADLE at the dosage of 0.05 mg/kg may be related to its antioxidant and antiapoptosis properties in the rabbit model of spinal cord I/R injury.

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Delta Opioid Receptor and Peptide: A Dynamic Therapy for Stroke and Other Neurological Disorders

Liska

Crowley

Lippert

et al. 2017

Handbook of Experimental Pharmacology

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Research of the opioid system and its composite receptors and ligands has revealed its promise as a potential therapy for neurodegenerative diseases such as stroke and Parkinson's Disease. In particular, delta opioid receptors (DORs) have been elucidated as a therapeutically distinguished subset of opioid receptors and a compelling target for novel intervention techniques. Research is progressively shedding light on the underlying mechanism of DORs and has revealed two mechanisms of DOR neuroprotection; DORs function to maintain ionic homeostasis and also to trigger endogenous neuroprotective pathways. Delta opioid agonists such as (D-Ala2, D-Leu5) enkephalin (DADLE) have been shown to promote neuronal survival and decrease apoptosis, resulting in a substantial amount of research for its application as a neurological therapeutic. Most notably, DADLE has demonstrated significant potential to reduce cell death following ischemic events. Current research is working to reveal the complex mechanisms of DADLE's neuroprotective properties. Ultimately, our knowledge of the DOR receptors and agonists has made the opioid system a promising target for therapeutic intervention in many neurological disorders.

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Dose-dependent neuroprotection of delta-opioid peptide [D-Ala 2 , D-Leu 5 ] enkephalin on spinal cord ischemia-reperfusion injury by regional perfusion into the abdominal aorta in rabbits

Abstract: These data revealed that regional administration of DADLE through the abdominal aorta provided dose-dependent protection on spinal cord I/R in rabbits.

Cited by 12 publications

References 24 publications

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

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

Antioxidative and Antiapoptotic Effects of Delta-Opioid Peptide [D-Ala2, D-Leu5] Enkephalin on Spinal Cord Ischemia-Reperfusion Injury in Rabbits

Delta Opioid Receptor and Peptide: A Dynamic Therapy for Stroke and Other Neurological Disorders

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