Neuropeptide role of α-Melanocyte-stimulating hormone against cerebral ischemia/reperfusion injury in type 1 diabetes

Abstract

Type 1 diabetic patients have higher risk of stroke than the general population. α-Melanocyte stimulating hormone (α-MSH) is a peptide derived from a precursor polypeptide, proopiomelanocortin. Several studies showed that α-MSH has protective effects against ischemia/reperfusion (I/R) induced organ damages. Therefore, we aimed to find the neuroprotective role of this peptide on I/R induced cerebral damage after experimental stroke associated with hyperglycemia using C57BL/6J Ins2Akita/+ mice. I/R injury was induced by blocking the right middle cerebral artery for 2 hours with reperfusion for 2 hours and 22 hours, respectively using the intraluminal method. Animals were treated intraperitoneally with either vehicle or α-MSH at 1 hour after ischemia and 1 hour after reperfusion. α-MSH treated animals has significantly higher survival rate with lower neurological scores. α-MSH significantly decreased relative infarct area, hemorrhage, glial cells activation as well as oxidative and nitrosative stress. Relative intensities of matrix metallopeptidases 9, cyclooxygenase 2 and nuclear factor-κB were significantly decreased while intensities of protein kinase b (also known as Akt), heme oxygenase (HO) 1, HO-2 and B-cell lymphoma 2 were significantly increased after α-MSH treatment. In addition, gene expressions of monocarboxylate transporter (MCT) 1, MCT-2 and activity-regulated cytoskeleton-associated protein were significantly higher in brain samples treated with α-MSH. Finally, % TUNEL was significantly lower in α-MSH treated brain slices. In conclusion, α-MSH is neuroprotective under hyperglycemic condition against I/R induced brain damage by its anti-inflammatory, anti-oxidative and anti-apoptotic properties. The α-MSH analogues may be potential therapeutic agents against stroke under hyperglycemic condition.