Protective effect of delta opioid receptor agonist (D-Ala2, D-Leu5) enkephalin on permanent focal cerebral ischemia in rats

Abstract

To investigate the effect of delta opioid receptor agonist (D-Ala, D-Leu) enkephalin (DADLE) on the permanent focal cerebral ischemia in rats. Thirty four male Sprague-Dawley rats were assigned randomly into three groups: sham group (group Sham, n=10), artificial cerebrospinal fluid group (group ACSF, n=12), and DADLE group (group DADLE, n=12). Permanent middle cerebral artery occlusion was performed to induce permanent focal cerebral ischemia in rats. Then, the animals in group DADLE and group ACSF were treated with DADLE or ACSF by an intracerebroventricular injection at 45 min after ischemia. Neurologic deficit scores were assessed according to the Garcia criterion at 24 h after ischemia. Infarct volume was determined using the 2,3,5-triphenyltetrazolium chloride staining method. The histological analysis was used to evaluate the extent of cerebral injury. Compared with the control group, the Garcia scores were significantly higher (P=0.000) and the infarct volumes (P=0.018) were significantly smaller in the DADLE treatment group at 24 h after ischemia. These neurologic changes were closely correlated with the outcome of the infarct volumes. In addition, the histological examination showed more intact neurons in rats treated with DADLE than those treated with ACSF at 24 h after ischemia (P=0.000). DADLE by intracerebroventricular administration at 45 min after ischemia can improve neurologic outcome and mitigate cortical neuronal injury induced by permanent focal cerebral ischemia in rats.

δ-Opioid receptor activation ameliorates lipopolysaccharide-induced inflammation and apoptosis by inhibiting the MAPK/caspase-3 pathway in BV2 microglial cells

“…More importantly, a growing body of evidence has shown that the neuroprotective effect of DOR activation is related to MAPK signalling during ischaemia/hypoxia. For example, treatment with the DOR agonist [D-Ala2, D-Leu5]-enkephalin (DADLE) extends the neuronal survival rate during permanent focal cerebral ischaemia in rats (Fu et al 2016). Perfusion with DADLE also provides neuroprotection against oxygen-glucose deprivation (OGD)-induced neuronal injury by affecting the phosphorylation of extracellular signal-regulated kinases (ERKs) and p38 but not c-Jun N-terminal kinase (JNK) (Ke et al 2009).…”

Synthesis of [18F]Fluoroarenes by Nucleophilic Radiofluorination of N‐Arylsydnones

“…Peptide 23 is a selective delta-opioid receptor agonist which displays protective effects towards the preservation of neurologic function and neuronal damage against hypoxic or ischemic induced brain injury. [27] Peptide 23 was functionalized with succinimidyl ester 22 to afford DIBAC-peptide conjugate 24 . The desired 4-[ 18 F]fluorophenyl sydnone 4b (6–10 mCi) was purified and isolated within 62 min from the end of bombardment in 21 ± 3% non-decay-corrected radiochemical yield (RCY) (n=17) with a specific activity of 1.3 Ci μmol −1 .…”

Delta Opioid Peptide Targets Brain Microvascular Endothelial Cells Reducing Apoptosis to Relieve Hypoxia-Ischemic/Reperfusion Injury

“…The rats in the sham group underwent the same surgical operations except for the monofilament insertion. Statistically, the total mortality was 21% [ 23 , 25 ].…”