Neuropeptide α-Melanocyte-Stimulating Hormone Promotes Neurological Recovery and Repairs Cerebral Ischemia/Reperfusion Injury in Type 1 Diabetes

Persons with type 1 diabetes have an increased risk of stroke compared with the general population. alpha-Melanocyte-stimulating hormone (alpha-MSH) is a neuropeptide that has protective effects against ischemia/reperfusion (I/R) induced organ damages. In this study, we aimed to investigate the neuroprotective role of this peptide on I/R induced brain damage after experimental stroke associated with hyperglycemia using C57BL/6J Ins2(Akita/+) mice. Experimental stroke was induced by blocking the right middle cerebral artery for 2 h with reperfusion for 2 and 22 h, respectively using the intraluminal method. Animals were treated intraperitoneally with or without alpha-MSH at 1 h after ischemia and 1 h after reperfusion. Significantly higher survival rate and lower neurological scores were recorded in animals injected with alpha-MSH. Similarly, neuron death, glial cells activation as well as oxidative and nitrosative stress were significantly decreased in alpha-MSH treated group. Relative intensities of matrix metallopeptidases 9, cyclooxygenase 2 and nuclear factor-kappa B were significantly decreased while intensities of Akt, heme oxygenase (HO) 1, HO-2 and B-cell lymphoma 2 were significantly increased after alpha-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 alpha-MSH, suggesting this peptide may have role in neuron survival by an involvement of lactate metabolism. In conclusion, alpha-MSH is neuroprotective under hyperglycemic condition against I/R induced brain damage by its anti-inflammatory, anti-oxidative and anti-apoptotic properties. The use of alpha-MSH analogues may be potential therapeutic agents for diabetic stroke.

Automated summary

alpha-Melanocyte-stimulating hormone (alpha-MSH) has neuroprotective effects against ischemia/reperfusion (I/R) induced brain damage in experimental stroke associated with hyperglycemia, reducing neuron death, inflammation, and oxidative stress. The use of alpha-MSH analogues may be a potential therapeutic strategy for diabetic stroke.