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

Brain : a Journal of Neurology
E Rocha-FerreiraAhad A Rahim

Abstract

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 dose...Continue Reading

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Citations

Apr 3, 2019·Brain Injury : [BI]·Damla ErbilHale Yapıcı Eser
Apr 8, 2020·Journal of Psychopharmacology·Patrícia Maidana MiguelLenir Orlandi Pereira
Jul 3, 2020·Developmental Medicine and Child Neurology·Kelly Q ZhouAlistair J Gunn
Jan 9, 2019·Frontiers in Cellular Neuroscience·Marco SancandiAudrey Mercer
Jun 28, 2019·Frontiers in Neuroscience·Ying-Jian SunGuang-Yu Li
Aug 2, 2019·Acta neurologica Belgica·Anqi Huang, Lihua Jia
May 22, 2020·Frontiers in Cellular Neuroscience·Laura Poupon-BejuitAhad A Rahim
Jan 1, 2021·Biochemical and Biophysical Research Communications·Saige YinXinwang Yang
Jun 23, 2021·Seminars in Fetal & Neonatal Medicine·Aravanan A ChakkarapaniUNKNOWN Newborn Brain Society Guidelines and Publications Committee

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