Single administration of tripeptide α-MSH(11-13) attenuates brain damage by reduced inflammation and apoptosis after experimental traumatic brain injury in mice.
Following traumatic brain injury (TBI) neuroinflammatory processes promote neuronal cell loss. Alpha-melanocyte-stimulating hormone (α-MSH) is a neuropeptide with immunomodulatory properties, which may offer neuroprotection. Due to short half-life and pigmentary side-effects of α-MSH, the C-terminal tripeptide α-MSH(11-13) may be an anti-inflammatory alternative. The present study investigated the mRNA concentrations of the precursor hormone proopiomelanocortin (POMC) and of melanocortin receptors 1 and 4 (MC1R/MC4R) in naive mice and 15 min, 6, 12, 24, and 48 h after controlled cortical impact (CCI). Regulation of POMC and MC4R expression did not change after trauma, while MC1R levels increased over time with a 3-fold maximum at 12 h compared to naive brain tissue. The effect of α-MSH(11-13) on secondary lesion volume determined in cresyl violet stained sections (intraperitoneal injection 30 min after insult of 1 mg/kg α-MSH(11-13) or 0.9% NaCl) showed a considerable smaller trauma in α-MSH(11-13) injected mice. The expression of the inflammatory markers TNF-α and IL-1β as well as the total amount of Iba-1 positive cells were not reduced. However, cell branch counting of Iba-1 positive cells revealed a reduced activation of microglia. Furthermore, tripeptide injection reduced neuronal apoptosis analyzed by cleaved caspase-3 and NeuN staining. Based on the results single α-MSH(11-13) administration offers a promising neuroprotective property by modulation of inflammation and prevention of apoptosis after traumatic brain injury.
Department of Anesthesiology, Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany.
Eva-Verena
EV
Schaible
Arne
A
Steinsträßer
Antje
A
Jahn-Eimermacher
Clara
C
Luh
Anne
A
Sebastiani
Frida
F
Kornes
Dana
D
Pieter
Michael K
MK
Schäfer
Kristin
K
Engelhard
Serge C
SC
Thal
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage*; D017209:Apoptosis / Q000187:drug effects*; D001921:Brain / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D001930:Brain Injuries / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism; D002135:Calcium-Binding Proteins / Q000378:metabolism; D015870:Gene Expression; D018836:Inflammation Mediators / Q000378:metabolism; D008297:Male; D009074:Melanocyte-Stimulating Hormones / Q000008:administration & dosage*; D051379:Mice; D008810:Mice, Inbred C57BL; D008840:Microfilament Proteins / Q000378:metabolism; D017628:Microglia / Q000187:drug effects / Q000378:metabolism; D010446:Peptide Fragments / Q000008:administration & dosage*; D011333:Pro-Opiomelanocortin / Q000235:genetics / Q000378:metabolism; D044102:Receptor, Melanocortin, Type 1 / Q000235:genetics / Q000378:metabolism; D044105:Receptor, Melanocortin, Type 4 / Q000235:genetics / Q000378:metabolism
C491049:Aif1 protein, mouse; D000893:Anti-Inflammatory Agents; D002135:Calcium-Binding Proteins; D018836:Inflammation Mediators; C574273:MC4R protein, mouse; D008840:Microfilament Proteins; D010446:Peptide Fragments; D044102:Receptor, Melanocortin, Type 1; D044105:Receptor, Melanocortin, Type 4; D011333:Pro-Opiomelanocortin; C043156:MSH (11-13); D009074:Melanocyte-Stimulating Hormones