title: New horizons for newborn brain protection: enhancing endogenous neuroprotection.
abstract: Intrapartum-related events are the third leading cause of childhood mortality worldwide and result in one million neurodisabled survivors each year. Infants exposed to a perinatal insult typically present with neonatal encephalopathy (NE). The contribution of pure hypoxia-ischaemia (HI) to NE has been debated; over the last decade, the sensitising effect of inflammation in the aetiology of NE and neurodisability is recognised. Therapeutic hypothermia is standard care for NE in high-income countries; however, its benefit in encephalopathic babies with sepsis or in those born following chorioamnionitis is unclear. It is now recognised that the phases of brain injury extend into a tertiary phase, which lasts for weeks to years after the initial insult and opens up new possibilities for therapy.There has been a recent focus on understanding endogenous neuroprotection and how to boost it or to supplement its effectors therapeutically once damage to the brain has occurred as in NE. In this review, we focus on strategies that can augment the body's own endogenous neuroprotection. We discuss in particular remote ischaemic postconditioning whereby endogenous brain tolerance can be activated through hypoxia/reperfusion stimuli started immediately after the index hypoxic-ischaemic insult. Therapeutic hypothermia, melatonin, erythropoietin and cannabinoids are examples of ways we can supplement the endogenous response to HI to obtain its full neuroprotective potential. Achieving the correct balance of interventions at the correct time in relation to the nature and stage of injury will be a significant challenge in the next decade.
authors.affiliation: Institute for Women's Health, University College London, London, UK.
authors.forename: K Jane
authors.initials: KJ
authors.lastname: Hassell
authors.affiliation: Institute for Women's Health, University College London, London, UK.
authors.forename: Mojgan
authors.initials: M
authors.lastname: Ezzati
authors.affiliation: Institute for Women's Health, University College London, London, UK.
authors.forename: Daniel
authors.initials: D
authors.lastname: Alonso-Alconada
authors.affiliation: The Hatter Cardiovascular Institute, Institute of Cardiovascular Science, NIHR University College London Hospitals Biomedical Research Centre, University College London Hospital & Medical School, London, UK.
authors.forename: Derek J
authors.initials: DJ
authors.lastname: Hausenloy
authors.affiliation: Institute for Women's Health, University College London, London, UK.
authors.forename: Nicola J
authors.initials: NJ
authors.lastname: Robertson
mesh_terms: D001238:Asphyxia Neonatorum / Q000188:drug therapy*; D001921:Brain / Q000503:physiopathology; D002186:Cannabinoids / Q000009:adverse effects / Q000627:therapeutic use; D004921:Erythropoietin / Q000009:adverse effects / Q000627:therapeutic use; D006801:Humans; D007036:Hypothermia, Induced / Q000009:adverse effects / Q000379:methods*; D020925:Hypoxia-Ischemia, Brain / Q000503:physiopathology / Q000628:therapy*; D007231:Infant, Newborn; D008550:Melatonin / Q000009:adverse effects / Q000627:therapeutic use; D000066829:Neuroprotection / Q000187:drug effects*; D018696:Neuroprotective Agents / Q000627:therapeutic use*
chemical_list: D002186:Cannabinoids; D018696:Neuroprotective Agents; D004921:Erythropoietin; D008550:Melatonin
keywords: Birth asphyxia; Melatonin; Neonatal encephalopathy; Neuroprotection; Post Conditioning