Skip to content

Study · Animal study (in vivo) · mouse · 2018

10 results

Neuroprotective exendin-4 enhances hypothermia therapy in a model of hypoxic-ischaemic encephalopathy.

Rocha-Ferreira E, Poupon L, Zelco A, Leverin AL, Nair S, Jonsdotter A, Carlsson Y, Thornton C, Hagberg H, Rahim AA

Brain : a journal of neurology1 Oct 2018Cited by 47 (Europe PMC)

PMID30165597 (opens in a new tab)PMCIDPMC6158761 (opens in a new tab)DOI10.1093/brain/awy220 (opens in a new tab)PepBankPUB-30165597
Download PDFPubMedAsk about this study
Jump to 10 results

Summary

Hypoxic-ischaemic encephalopathy remains a global health burden. Despite medical advances and treatment with therapeutic hypothermia, over 50% of cooled infants are not protected and still develop lifelong neurodisabilities, including cerebral palsy. Furthermore, hypothermia is not used in preterm cases or low resource settings. Alternatives or adjunct therapies are urgently needed. Exendin-4 is a drug used to treat type 2 diabetes mellitus that has also demonstrated neuroprotective properties, and is currently being tested in clinical trials for Alzheimer's and Parkinson's diseases. Therefore, we hypothesized a neuroprotective effect for exendin-4 in neonatal neurodisorders, particularly in the treatment of neonatal hypoxic-ischaemic encephalopathy. Initially, we confirmed that the glucagon like peptide 1 receptor (GLP1R) was expressed in the human neonatal brain and in murine neurons at postnatal Day 7 (human equivalent late preterm) and postnatal Day 10 (term). Using a well characterized mouse model of neonatal hypoxic-ischaemic brain injury, we investigated the potential neuroprotective effect of exendin-4 in both postnatal Day 7 and 10 mice. An optimal exendin-4 treatment dosing regimen was identified, where four high doses (0.5 µg/g) starting at 0 h, then at 12 h, 24 h and 36 h after postnatal Day 7 hypoxic-ischaemic insult resulted in significant brain neuroprotection. Furthermore, neuroprotection was sustained even when treatment using exendin-4 was delayed by 2 h post hypoxic-ischaemic brain injury. This protective effect was observed in various histopathological markers: tissue infarction, cell death, astrogliosis, microglial and endothelial activation. Blood glucose levels were not altered by high dose exendin-4 administration when compared to controls. Exendin-4 administration did not result in adverse organ histopathology (haematoxylin and eosin) or inflammation (CD68). Despite initial reduced weight gain, animals restored weight gain following end of treatment. Overall high dose exendin-4 administration was well tolerated. To mimic the clinical scenario, postnatal Day 10 mice underwent exendin-4 and therapeutic hypothermia treatment, either alone or in combination, and brain tissue loss was assessed after 1 week. Exendin-4 treatment resulted in significant neuroprotection alone, and enhanced the cerebroprotective effect of therapeutic hypothermia. In summary, the safety and tolerance of high dose exendin-4 administrations, combined with its neuroprotective effect alone or in conjunction with clinically relevant hypothermia make the repurposing of exendin-4 for the treatment of neonatal hypoxic-ischaemic encephalopathy particularly promising.
CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study10

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

  1. 01AnimalAnimal study (in vivo)Efficacy outcome

    In postnatal Day 7 mice with hypoxic-ischaemic injury, four high exendin‑4 doses starting immediately produced significant brain neuroprotection.

    In plain wordsIn mice with neonatal brain injury, four high exendin‑4 doses starting immediately significantly protected the brain.

    Peptide
    Exenatide (exendin-4)
    Outcome
    IncreaseBrain neuroprotection with immediate treatment
    Study

    mousen: not reported in source

    neonatal hypoxic-ischaemic brain injury
    Outcome group
    Neuroprotection · Nervous system and cognition
    Studied dose
    four doses of 0.5 µg/g at 0, 12, 24 and 36 hAs given in this study (mouse).

    Source sentences

    Summary
    An optimal exendin-4 treatment dosing regimen was identified, where four high doses (0.5 µg/g) starting at 0 h, then at 12 h, 24 h and 36 h after postnatal Day 7 hypoxic-ischaemic insult resulted in significant brain neuroprotection.
    1 context sentence
    Summary · context
    Using a well characterized mouse model of neonatal hypoxic-ischaemic brain injury, we investigated the potential neuroprotective effect of exendin-4 in both postnatal Day 7 and 10 mice.
  2. 02AnimalAnimal study (in vivo)Efficacy outcome

    In mice with neonatal hypoxic-ischaemic injury, exendin‑4 retained neuroprotection when treatment started 2 h after injury.

    In plain wordsIn mice with neonatal brain injury, exendin‑4 remained protective when treatment started 2 h after injury.

    Peptide
    Exenatide (exendin-4)
    Outcome
    IncreaseBrain neuroprotection with delayed treatment
    Study

    mousen: not reported in source

    neonatal hypoxic-ischaemic brain injury
    Outcome group
    Neuroprotection · Nervous system and cognition
    Studied dose
    Dose not stated

    Source sentences

    Summary
    Furthermore, neuroprotection was sustained even when treatment using exendin-4 was delayed by 2 h post hypoxic-ischaemic brain injury.
    1 context sentence
    Summary · context
    Using a well characterized mouse model of neonatal hypoxic-ischaemic brain injury, we investigated the potential neuroprotective effect of exendin-4 in both postnatal Day 7 and 10 mice.
  3. 03AnimalAnimal study (in vivo)Efficacy outcome

    In mice with neonatal hypoxic-ischaemic injury, exendin‑4 neuroprotection appeared across several histopathological markers without separately stated marker results.

    In plain wordsIn mice with neonatal brain injury, exendin‑4 showed protection across several tissue markers.

    Peptide
    Exenatide (exendin-4)
    Outcome
    IncreaseHistopathological neuroprotection
    Study

    mousen: not reported in source

    neonatal hypoxic-ischaemic brain injury
    Outcome group
    Neuroprotection · Nervous system and cognition
    Studied dose
    Dose not stated

    Source sentences

    Summary
    This protective effect was observed in various histopathological markers: tissue infarction, cell death, astrogliosis, microglial and endothelial activation.
    2 context sentences
    Summary · context
    An optimal exendin-4 treatment dosing regimen was identified, where four high doses (0.5 µg/g) starting at 0 h, then at 12 h, 24 h and 36 h after postnatal Day 7 hypoxic-ischaemic insult resulted in significant brain neuroprotection.
    Summary · context
    Using a well characterized mouse model of neonatal hypoxic-ischaemic brain injury, we investigated the potential neuroprotective effect of exendin-4 in both postnatal Day 7 and 10 mice.
  4. 04AnimalAnimal study (in vivo)Safety outcome

    In mice with neonatal brain injury, high-dose exendin‑4 did not alter blood glucose versus controls.

    In plain wordsIn mice with neonatal brain injury, high-dose exendin‑4 did not change blood glucose compared with controls.

    Peptide
    Exenatide (exendin-4)
    Outcome
    No significant changeBlood glucose
    Study

    mousen: not reported in source

    neonatal hypoxic-ischaemic brain injury
    Comparator
    controls
    Outcome group
    Glycemic control · Metabolic and weight
    Studied dose
    Dose not stated

    Source sentences

    Summary
    Blood glucose levels were not altered by high dose exendin-4 administration when compared to controls.
    1 context sentence
    Summary · context
    Using a well characterized mouse model of neonatal hypoxic-ischaemic brain injury, we investigated the potential neuroprotective effect of exendin-4 in both postnatal Day 7 and 10 mice.
  5. 05AnimalAnimal study (in vivo)Safety outcome

    In mice with neonatal brain injury, exendin‑4 did not cause adverse organ histopathology on haematoxylin and eosin examination.

    In plain wordsIn mice with neonatal brain injury, exendin‑4 did not produce adverse organ histopathology.

    Peptide
    Exenatide (exendin-4)
    Outcome
    Not applicableAdverse organ histopathology
    Study

    mousen: not reported in source

    neonatal hypoxic-ischaemic brain injury
    Outcome group
    Adverse events · Whole body
    Studied dose
    Dose not stated

    Source sentences

    Summary
    Exendin-4 administration did not result in adverse organ histopathology (haematoxylin and eosin) or inflammation (CD68).
    1 context sentence
    Summary · context
    Using a well characterized mouse model of neonatal hypoxic-ischaemic brain injury, we investigated the potential neuroprotective effect of exendin-4 in both postnatal Day 7 and 10 mice.
  6. 06AnimalAnimal study (in vivo)Safety outcome

    In mice with neonatal brain injury, exendin‑4 did not cause organ inflammation assessed by CD68.

    In plain wordsIn mice with neonatal brain injury, exendin‑4 did not produce organ inflammation assessed by CD68.

    Peptide
    Exenatide (exendin-4)
    Outcome
    Not applicableOrgan inflammation
    Study

    mousen: not reported in source

    neonatal hypoxic-ischaemic brain injury
    Outcome group
    Inflammation markers · Immune and inflammation
    Studied dose
    Dose not stated

    Source sentences

    Summary
    Exendin-4 administration did not result in adverse organ histopathology (haematoxylin and eosin) or inflammation (CD68).
    1 context sentence
    Summary · context
    Using a well characterized mouse model of neonatal hypoxic-ischaemic brain injury, we investigated the potential neuroprotective effect of exendin-4 in both postnatal Day 7 and 10 mice.
  7. 07AnimalAnimal study (in vivo)Safety outcome

    In mice with neonatal brain injury, exendin‑4 initially reduced weight gain, which recovered after treatment ended.

    In plain wordsIn mice with neonatal brain injury, weight gain initially decreased during exendin‑4 treatment and recovered after treatment ended.

    Peptide
    Exenatide (exendin-4)
    Outcome
    MixedWeight gain
    Study

    mousen: not reported in source

    neonatal hypoxic-ischaemic brain injury
    Outcome group
    Body weight · Metabolic and weight
    Studied dose
    Dose not stated

    Source sentences

    Summary
    Despite initial reduced weight gain, animals restored weight gain following end of treatment.
    1 context sentence
    Summary · context
    Using a well characterized mouse model of neonatal hypoxic-ischaemic brain injury, we investigated the potential neuroprotective effect of exendin-4 in both postnatal Day 7 and 10 mice.
  8. 08AnimalAnimal study (in vivo)Safety outcome

    In mice with neonatal brain injury, high-dose exendin‑4 was well tolerated overall.

    In plain wordsIn mice with neonatal brain injury, high-dose exendin‑4 was well tolerated overall.

    Peptide
    Exenatide (exendin-4)
    Outcome
    Not applicableHigh-dose tolerability
    Study

    mousen: not reported in source

    neonatal hypoxic-ischaemic brain injury
    Outcome group
    Adverse events · Whole body
    Studied dose
    Dose not stated

    Source sentences

    Summary
    Overall high dose exendin-4 administration was well tolerated.
    1 context sentence
    Summary · context
    Using a well characterized mouse model of neonatal hypoxic-ischaemic brain injury, we investigated the potential neuroprotective effect of exendin-4 in both postnatal Day 7 and 10 mice.
  9. 09AnimalAnimal study (in vivo)Efficacy outcome

    In postnatal Day 10 mice with hypoxic-ischaemic injury, exendin‑4 alone produced significant neuroprotection.

    In plain wordsIn mice with neonatal brain injury, exendin‑4 alone significantly protected the brain.

    Peptide
    Exenatide (exendin-4)
    Outcome
    IncreaseNeuroprotection at postnatal Day 10
    Study

    mousen: not reported in source

    neonatal hypoxic-ischaemic brain injury
    Outcome group
    Neuroprotection · Nervous system and cognition
    Studied dose
    Dose not stated

    Source sentences

    Summary
    Exendin-4 treatment resulted in significant neuroprotection alone, and enhanced the cerebroprotective effect of therapeutic hypothermia.
    2 context sentences
    Summary · context
    To mimic the clinical scenario, postnatal Day 10 mice underwent exendin-4 and therapeutic hypothermia treatment, either alone or in combination, and brain tissue loss was assessed after 1 week.
    Summary · context
    Using a well characterized mouse model of neonatal hypoxic-ischaemic brain injury, we investigated the potential neuroprotective effect of exendin-4 in both postnatal Day 7 and 10 mice.
  10. 10AnimalAnimal study (in vivo)Efficacy outcome

    In postnatal Day 10 mice with hypoxic-ischaemic injury, exendin‑4 enhanced the cerebroprotective effect of therapeutic hypothermia.

    In plain wordsIn mice with neonatal brain injury, exendin‑4 increased brain protection compared with hypothermia alone.

    Peptide
    Exenatide (exendin-4)
    Outcome
    IncreaseAdjunct neuroprotection with hypothermia
    Study

    mousen: not reported in source

    neonatal hypoxic-ischaemic brain injury
    Comparator
    therapeutic hypothermia alone
    Outcome group
    Neuroprotection · Nervous system and cognition
    Studied dose
    Dose not stated

    Source sentences

    Summary
    Exendin-4 treatment resulted in significant neuroprotection alone, and enhanced the cerebroprotective effect of therapeutic hypothermia.
    2 context sentences
    Summary · context
    To mimic the clinical scenario, postnatal Day 10 mice underwent exendin-4 and therapeutic hypothermia treatment, either alone or in combination, and brain tissue loss was assessed after 1 week.
    Summary · context
    Using a well characterized mouse model of neonatal hypoxic-ischaemic brain injury, we investigated the potential neuroprotective effect of exendin-4 in both postnatal Day 7 and 10 mice.

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

    22 Oct 2026, 02:26 UTC

    Study results updated

  2. Version 1

    21 Oct 2026, 18:59 UTC

    First added · source update from Europe PMC

Subjects

Terms as the source lists them.

PepBank is a research reference. Talk to a doctor before you use any peptide.