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. α-Melanocyte-stimulating hormone (α-MSH) is a neuropeptide that has protective effects against ischemia/reperfusion (I/R) induced organ damages. In this study, we aimed to investigate the neuroprotect...

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Bibliographic Details
Published in:Neurochemical research 2022-02, Vol.47 (2), p.394-408
Main Authors: Goit, Rajesh Kumar, Ng, Tsz Chung, Tam, Ka Cheung, Tsang, Jessica K. W., Taylor, Andrew W., Lo, Amy C. Y.
Format: Article
Language:English
Subjects:
AKT protein
alpha-MSH - pharmacology
alpha-MSH - therapeutic use
Animals
Apoptosis
ARC protein
B-cell lymphoma
Beta cells
Biochemistry
Biomedical and Life Sciences
Biomedicine
Brain
Brain damage
Brain injury
Brain Ischemia - drug therapy
Cell activation
Cell Biology
Cell death
Chemical compounds
Cyclooxygenase-2
Cytoskeleton
Diabetes
Diabetes mellitus
Diabetes mellitus (insulin dependent)
Diabetes Mellitus, Type 1 - drug therapy
Glial cells
Health risks
Heme
Humans
Hyperglycemia
Inflammation
Ischemia
Lactic acid
Lymphoma
Matrix metalloproteinases
Melanocyte-stimulating hormone
Metabolism
Mice
Mice, Inbred C57BL
Neurochemistry
Neurology
Neuronal-glial interactions
Neuropeptides
Neuroprotection
Neurosciences
Original Paper
Oxidative stress
Oxygenase
Peptides
Pharmacology
Reperfusion
Reperfusion Injury - metabolism
Stroke
Survival
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Summary:Persons with type 1 diabetes have an increased risk of stroke compared with the general population. α-Melanocyte-stimulating hormone (α-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 α-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 α-MSH. Similarly, neuron death, glial cells activation as well as oxidative and nitrosative stress were significantly decreased in α-MSH treated group. Relative intensities of matrix metallopeptidases 9, cyclooxygenase 2 and nuclear factor-κB were significantly decreased while intensities of 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, suggesting this peptide may have role in neuron survival by an involvement of lactate metabolism. 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 use of α-MSH analogues may be potential therapeutic agents for diabetic stroke.
ISSN:0364-3190
1573-6903
DOI:10.1007/s11064-021-03453-4