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Study · Animal study (in vivo) · mouse · 2019

15 results

NDP-MSH binding melanocortin-1 receptor ameliorates neuroinflammation and BBB disruption through CREB/Nr4a1/NF-κB pathway after intracerebral hemorrhage in mice.

Wu X, Fu S, Liu Y, Luo H, Li F, Wang Y, Gao M, Cheng Y, Xie Z

Journal of neuroinflammation28 Oct 2019Cited by 92 (Europe PMC)

PMID31660977 (opens in a new tab)PMCIDPMC6816206 (opens in a new tab)DOI10.1186/s12974-019-1591-4 (opens in a new tab)PepBankPUB-31660977
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Summary

BackgroundNeuroinflammation and blood-brain barrier (BBB) disruption are two vital mechanisms of secondary brain injury following intracerebral hemorrhage (ICH). Recently, melanocortin-1 receptor (Mc1r) activation by Nle4-D-Phe7-α-MSH (NDP-MSH) was shown to play a neuroprotective role in an experimental autoimmune encephalomyelitis (EAE) mouse model. This study aimed to investigate whether NDP-MSH could alleviate neuroinflammation and BBB disruption after experimental ICH, as well as the potential mechanisms of its neuroprotective roles.MethodsTwo hundred and eighteen male C57BL/6 mice were subjected to autologous blood-injection ICH model. NDP-MSH, an agonist of Mc1r, was administered intraperitoneally injected at 1 h after ICH insult. To further explore the related protective mechanisms, Mc1r small interfering RNA (Mc1r siRNA) and nuclear receptor subfamily 4 group A member 1 (Nr4a1) siRNA were administered via intracerebroventricular (i.c.v) injection before ICH induction. Neurological test, BBB permeability, brain water content, immunofluorescence staining, and Western blot analysis were implemented.ResultsThe Expression of Mc1r was significantly increased after ICH. Mc1r was mainly expressed in microglia, astrocytes, and endothelial cells following ICH. Treatment with NDP-MSH remarkably improved neurological function and reduced BBB disruption, brain water content, and the number of microglia in the peri-hematoma tissue after ICH. Meanwhile, the administration of NDP-MSH significantly reduced the expression of p-NF-κB p65, IL-1β, TNF-α, and MMP-9 and increased the expression of p-CREB, Nr4a1, ZO-1, occludin, and Lama5. Inversely, the knockdown of Mc1r or Nr4a1 abolished the neuroprotective effects of NDP-MSH.ConclusionsTaken together, NDP-MSH binding Mc1r attenuated neuroinflammation and BBB disruption and improved neurological deficits, at least in part through CREB/Nr4a1/NF-κB pathway after ICH.
CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study15

15 results from studies that gave the peptide. No result from this study comes from people.

  1. 01AnimalAnimal study (in vivo)Efficacy outcome

    In mice with intracerebral hemorrhage, NDP-MSH improved neurological function.

    In plain wordsIn mice with a brain bleed, NDP-MSH improved neurological function.

    Peptide
    Melanotan I (afamelanotide)
    Outcome
    IncreaseNeurological function after ICH
    Study

    mousen: not reported in source

    Autologous blood-injection intracerebral hemorrhage (ICH) model
    Outcome group
    Neuroprotection · Nervous system and cognition
    Studied dose
    Dose not stated · intraperitonealAs given in this study (mouse).

    Source sentences

    Summary
    Treatment with NDP-MSH remarkably improved neurological function
    2 context sentences
    Summary · context
    Two hundred and eighteen male C57BL/6 mice were subjected to autologous blood-injection ICH model.
    Summary · context
    NDP-MSH, an agonist of Mc1r, was administered intraperitoneally injected at 1 h after ICH insult.
  2. 02AnimalAnimal study (in vivo)Efficacy outcome

    In mice with intracerebral hemorrhage, NDP-MSH reduced blood-brain barrier disruption.

    In plain wordsIn mice with a brain bleed, NDP-MSH reduced damage to the blood-brain barrier.

    Peptide
    Melanotan I (afamelanotide)
    Outcome
    DecreaseBBB disruption after ICH
    Study

    mousen: not reported in source

    Autologous blood-injection intracerebral hemorrhage (ICH) model
    Outcome group
    Neuroprotection · Nervous system and cognition
    Studied dose
    Dose not stated · intraperitonealAs given in this study (mouse).

    Source sentences

    Summary
    reduced BBB disruption, brain water content, and the number of microglia in the peri-hematoma tissue after ICH.
    2 context sentences
    Summary · context
    Two hundred and eighteen male C57BL/6 mice were subjected to autologous blood-injection ICH model.
    Summary · context
    NDP-MSH, an agonist of Mc1r, was administered intraperitoneally injected at 1 h after ICH insult.
  3. 03AnimalAnimal study (in vivo)Efficacy outcome

    In mice with intracerebral hemorrhage, NDP-MSH reduced brain water content.

    In plain wordsIn mice with a brain bleed, NDP-MSH reduced brain swelling as measured by water content.

    Peptide
    Melanotan I (afamelanotide)
    Outcome
    DecreaseBrain water content after ICH
    Study

    mousen: not reported in source

    Autologous blood-injection intracerebral hemorrhage (ICH) model
    Outcome group
    Neuroprotection · Nervous system and cognition
    Studied dose
    Dose not stated · intraperitonealAs given in this study (mouse).

    Source sentences

    Summary
    reduced BBB disruption, brain water content, and the number of microglia in the peri-hematoma tissue after ICH.
    2 context sentences
    Summary · context
    Two hundred and eighteen male C57BL/6 mice were subjected to autologous blood-injection ICH model.
    Summary · context
    NDP-MSH, an agonist of Mc1r, was administered intraperitoneally injected at 1 h after ICH insult.
  4. 04AnimalAnimal study (in vivo)Efficacy outcome

    In mice with intracerebral hemorrhage, NDP-MSH reduced the number of microglia in the peri-hematoma tissue.

    In plain wordsIn mice with a brain bleed, NDP-MSH reduced the number of microglia around the bleed.

    Peptide
    Melanotan I (afamelanotide)
    Outcome
    DecreaseMicroglia number in peri-hematoma tissue
    Study

    mousen: not reported in source

    Autologous blood-injection intracerebral hemorrhage (ICH) model
    Outcome group
    Inflammation markers · Nervous system and cognition
    Studied dose
    Dose not stated · intraperitonealAs given in this study (mouse).

    Source sentences

    Summary
    reduced BBB disruption, brain water content, and the number of microglia in the peri-hematoma tissue after ICH.
    2 context sentences
    Summary · context
    Two hundred and eighteen male C57BL/6 mice were subjected to autologous blood-injection ICH model.
    Summary · context
    NDP-MSH, an agonist of Mc1r, was administered intraperitoneally injected at 1 h after ICH insult.
  5. 05AnimalAnimal study (in vivo)Mechanism

    In mice with intracerebral hemorrhage, NDP-MSH reduced the expression of p-NF-kB p65.

    In plain wordsIn mice with a brain bleed, NDP-MSH lowered the inflammation signal p-NF-kB p65.

    Peptide
    Melanotan I (afamelanotide)
    Outcome
    Decreasep-NF-kB p65 expression
    Study

    mousen: not reported in source

    Autologous blood-injection intracerebral hemorrhage (ICH) model
    Outcome group
    Inflammation markers · Nervous system and cognition
    Studied dose
    Dose not stated · intraperitonealAs given in this study (mouse).

    Source sentences

    Summary
    Meanwhile, the administration of NDP-MSH significantly reduced the expression of p-NF-κB p65, IL-1β, TNF-α, and MMP-9 and increased the expression of p-CREB, Nr4a1, ZO-1, occludin, and Lama5.
    2 context sentences
    Summary · context
    Two hundred and eighteen male C57BL/6 mice were subjected to autologous blood-injection ICH model.
    Summary · context
    NDP-MSH, an agonist of Mc1r, was administered intraperitoneally injected at 1 h after ICH insult.
  6. 06AnimalAnimal study (in vivo)Mechanism

    In mice with intracerebral hemorrhage, NDP-MSH reduced the expression of IL-1beta.

    In plain wordsIn mice with a brain bleed, NDP-MSH lowered the inflammation marker IL-1beta.

    Peptide
    Melanotan I (afamelanotide)
    Outcome
    DecreaseIL-1beta expression
    Study

    mousen: not reported in source

    Autologous blood-injection intracerebral hemorrhage (ICH) model
    Outcome group
    Inflammation markers · Nervous system and cognition
    Studied dose
    Dose not stated · intraperitonealAs given in this study (mouse).

    Source sentences

    Summary
    Meanwhile, the administration of NDP-MSH significantly reduced the expression of p-NF-κB p65, IL-1β, TNF-α, and MMP-9 and increased the expression of p-CREB, Nr4a1, ZO-1, occludin, and Lama5.
    2 context sentences
    Summary · context
    Two hundred and eighteen male C57BL/6 mice were subjected to autologous blood-injection ICH model.
    Summary · context
    NDP-MSH, an agonist of Mc1r, was administered intraperitoneally injected at 1 h after ICH insult.
  7. 07AnimalAnimal study (in vivo)Mechanism

    In mice with intracerebral hemorrhage, NDP-MSH reduced the expression of TNF-alpha.

    In plain wordsIn mice with a brain bleed, NDP-MSH lowered the inflammation marker TNF-alpha.

    Peptide
    Melanotan I (afamelanotide)
    Outcome
    DecreaseTNF-alpha expression
    Study

    mousen: not reported in source

    Autologous blood-injection intracerebral hemorrhage (ICH) model
    Outcome group
    Inflammation markers · Nervous system and cognition
    Studied dose
    Dose not stated · intraperitonealAs given in this study (mouse).

    Source sentences

    Summary
    Meanwhile, the administration of NDP-MSH significantly reduced the expression of p-NF-κB p65, IL-1β, TNF-α, and MMP-9 and increased the expression of p-CREB, Nr4a1, ZO-1, occludin, and Lama5.
    2 context sentences
    Summary · context
    Two hundred and eighteen male C57BL/6 mice were subjected to autologous blood-injection ICH model.
    Summary · context
    NDP-MSH, an agonist of Mc1r, was administered intraperitoneally injected at 1 h after ICH insult.
  8. 08AnimalAnimal study (in vivo)Mechanism

    In mice with intracerebral hemorrhage, NDP-MSH reduced the expression of MMP-9.

    In plain wordsIn mice with a brain bleed, NDP-MSH lowered the tissue-damaging enzyme MMP-9.

    Peptide
    Melanotan I (afamelanotide)
    Outcome
    DecreaseMMP-9 expression
    Study

    mousen: not reported in source

    Autologous blood-injection intracerebral hemorrhage (ICH) model
    Outcome group
    Inflammation markers · Nervous system and cognition
    Studied dose
    Dose not stated · intraperitonealAs given in this study (mouse).

    Source sentences

    Summary
    Meanwhile, the administration of NDP-MSH significantly reduced the expression of p-NF-κB p65, IL-1β, TNF-α, and MMP-9 and increased the expression of p-CREB, Nr4a1, ZO-1, occludin, and Lama5.
    2 context sentences
    Summary · context
    Two hundred and eighteen male C57BL/6 mice were subjected to autologous blood-injection ICH model.
    Summary · context
    NDP-MSH, an agonist of Mc1r, was administered intraperitoneally injected at 1 h after ICH insult.
  9. 09AnimalAnimal study (in vivo)Mechanism

    In mice with intracerebral hemorrhage, NDP-MSH increased the expression of p-CREB.

    In plain wordsIn mice with a brain bleed, NDP-MSH raised the protective signal p-CREB.

    Peptide
    Melanotan I (afamelanotide)
    Outcome
    Increasep-CREB expression
    Study

    mousen: not reported in source

    Autologous blood-injection intracerebral hemorrhage (ICH) model
    Outcome group
    Receptor activity and mechanism · Nervous system and cognition
    Studied dose
    Dose not stated · intraperitonealAs given in this study (mouse).

    Source sentences

    Summary
    Meanwhile, the administration of NDP-MSH significantly reduced the expression of p-NF-κB p65, IL-1β, TNF-α, and MMP-9 and increased the expression of p-CREB, Nr4a1, ZO-1, occludin, and Lama5.
    2 context sentences
    Summary · context
    Two hundred and eighteen male C57BL/6 mice were subjected to autologous blood-injection ICH model.
    Summary · context
    NDP-MSH, an agonist of Mc1r, was administered intraperitoneally injected at 1 h after ICH insult.
  10. 10AnimalAnimal study (in vivo)Mechanism

    In mice with intracerebral hemorrhage, NDP-MSH increased the expression of Nr4a1.

    In plain wordsIn mice with a brain bleed, NDP-MSH raised the protective protein Nr4a1.

    Peptide
    Melanotan I (afamelanotide)
    Outcome
    IncreaseNr4a1 expression
    Study

    mousen: not reported in source

    Autologous blood-injection intracerebral hemorrhage (ICH) model
    Outcome group
    Receptor activity and mechanism · Nervous system and cognition
    Studied dose
    Dose not stated · intraperitonealAs given in this study (mouse).

    Source sentences

    Summary
    Meanwhile, the administration of NDP-MSH significantly reduced the expression of p-NF-κB p65, IL-1β, TNF-α, and MMP-9 and increased the expression of p-CREB, Nr4a1, ZO-1, occludin, and Lama5.
    2 context sentences
    Summary · context
    Two hundred and eighteen male C57BL/6 mice were subjected to autologous blood-injection ICH model.
    Summary · context
    NDP-MSH, an agonist of Mc1r, was administered intraperitoneally injected at 1 h after ICH insult.
  11. 11AnimalAnimal study (in vivo)Mechanism

    In mice with intracerebral hemorrhage, NDP-MSH increased the expression of the tight-junction protein ZO-1.

    In plain wordsIn mice with a brain bleed, NDP-MSH raised levels of ZO-1, a protein that holds the blood-brain barrier together.

    Peptide
    Melanotan I (afamelanotide)
    Outcome
    IncreaseZO-1 expression
    Study

    mousen: not reported in source

    Autologous blood-injection intracerebral hemorrhage (ICH) model
    Outcome group
    Neuroprotection · Nervous system and cognition
    Studied dose
    Dose not stated · intraperitonealAs given in this study (mouse).

    Source sentences

    Summary
    Meanwhile, the administration of NDP-MSH significantly reduced the expression of p-NF-κB p65, IL-1β, TNF-α, and MMP-9 and increased the expression of p-CREB, Nr4a1, ZO-1, occludin, and Lama5.
    2 context sentences
    Summary · context
    Two hundred and eighteen male C57BL/6 mice were subjected to autologous blood-injection ICH model.
    Summary · context
    NDP-MSH, an agonist of Mc1r, was administered intraperitoneally injected at 1 h after ICH insult.
  12. 12AnimalAnimal study (in vivo)Mechanism

    In mice with intracerebral hemorrhage, NDP-MSH increased the expression of the tight-junction protein occludin.

    In plain wordsIn mice with a brain bleed, NDP-MSH raised levels of occludin, a protein that holds the blood-brain barrier together.

    Peptide
    Melanotan I (afamelanotide)
    Outcome
    IncreaseOccludin expression
    Study

    mousen: not reported in source

    Autologous blood-injection intracerebral hemorrhage (ICH) model
    Outcome group
    Neuroprotection · Nervous system and cognition
    Studied dose
    Dose not stated · intraperitonealAs given in this study (mouse).

    Source sentences

    Summary
    Meanwhile, the administration of NDP-MSH significantly reduced the expression of p-NF-κB p65, IL-1β, TNF-α, and MMP-9 and increased the expression of p-CREB, Nr4a1, ZO-1, occludin, and Lama5.
    2 context sentences
    Summary · context
    Two hundred and eighteen male C57BL/6 mice were subjected to autologous blood-injection ICH model.
    Summary · context
    NDP-MSH, an agonist of Mc1r, was administered intraperitoneally injected at 1 h after ICH insult.
  13. 13AnimalAnimal study (in vivo)Mechanism

    In mice with intracerebral hemorrhage, NDP-MSH increased the expression of Lama5.

    In plain wordsIn mice with a brain bleed, NDP-MSH raised levels of Lama5, a blood-brain barrier protein.

    Peptide
    Melanotan I (afamelanotide)
    Outcome
    IncreaseLama5 expression
    Study

    mousen: not reported in source

    Autologous blood-injection intracerebral hemorrhage (ICH) model
    Outcome group
    Neuroprotection · Nervous system and cognition
    Studied dose
    Dose not stated · intraperitonealAs given in this study (mouse).

    Source sentences

    Summary
    Meanwhile, the administration of NDP-MSH significantly reduced the expression of p-NF-κB p65, IL-1β, TNF-α, and MMP-9 and increased the expression of p-CREB, Nr4a1, ZO-1, occludin, and Lama5.
    2 context sentences
    Summary · context
    Two hundred and eighteen male C57BL/6 mice were subjected to autologous blood-injection ICH model.
    Summary · context
    NDP-MSH, an agonist of Mc1r, was administered intraperitoneally injected at 1 h after ICH insult.
  14. 14AnimalAnimal study (in vivo)Mechanism

    In mice with intracerebral hemorrhage, knockdown of Mc1r abolished the neuroprotective effects of NDP-MSH.

    In plain wordsIn mice with a brain bleed, switching off the Mc1r receptor removed the protective effects of NDP-MSH.

    Peptide
    Melanotan I (afamelanotide)
    Outcome
    Not applicableEffect of Mc1r knockdown on NDP-MSH protection
    Study

    mousen: not reported in source

    Autologous blood-injection intracerebral hemorrhage (ICH) model
    Outcome group
    Receptor activity and mechanism · Nervous system and cognition
    Studied dose
    Dose not stated · intraperitonealAs given in this study (mouse).

    Source sentences

    Summary
    Inversely, the knockdown of Mc1r or Nr4a1 abolished the neuroprotective effects of NDP-MSH.
    2 context sentences
    Summary · context
    Two hundred and eighteen male C57BL/6 mice were subjected to autologous blood-injection ICH model.
    Summary · context
    NDP-MSH, an agonist of Mc1r, was administered intraperitoneally injected at 1 h after ICH insult.
  15. 15AnimalAnimal study (in vivo)Mechanism

    In mice with intracerebral hemorrhage, knockdown of Nr4a1 abolished the neuroprotective effects of NDP-MSH.

    In plain wordsIn mice with a brain bleed, switching off Nr4a1 removed the protective effects of NDP-MSH.

    Peptide
    Melanotan I (afamelanotide)
    Outcome
    Not applicableEffect of Nr4a1 knockdown on NDP-MSH protection
    Study

    mousen: not reported in source

    Autologous blood-injection intracerebral hemorrhage (ICH) model
    Outcome group
    Receptor activity and mechanism · Nervous system and cognition
    Studied dose
    Dose not stated · intraperitonealAs given in this study (mouse).

    Source sentences

    Summary
    Inversely, the knockdown of Mc1r or Nr4a1 abolished the neuroprotective effects of NDP-MSH.
    2 context sentences
    Summary · context
    Two hundred and eighteen male C57BL/6 mice were subjected to autologous blood-injection ICH model.
    Summary · context
    NDP-MSH, an agonist of Mc1r, was administered intraperitoneally injected at 1 h after ICH insult.

AI wrote and checked these results. AI can make mistakes, so check important results against the source.

Version history

PepBank keeps every version of the data on this study. Status changes from Retraction Watch, Europe PMC and Crossref are listed with their source.

  1. Version 2Current

    13 Oct 2026, 21:44 UTC

    Study results updated

  2. Version 1

    13 Oct 2026, 16:31 UTC

    First added · source update from Europe PMC

Subjects

Terms as the source lists them.

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