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Therapies for neonatal encephalopathy: Targeting the latent, secondary and tertiary phases of evolving brain injury

Chakkarapani, AA; Aly, H; Benders, M; Cotten, CM; El-Dib, M; Gressens, P; Hagberg, H; ... Newborn Brain Society Guidelines and Publications Committee; + view all (2021) Therapies for neonatal encephalopathy: Targeting the latent, secondary and tertiary phases of evolving brain injury. Seminars in Fetal & Neonatal Medicine , 26 (5) , Article 101256. 10.1016/j.siny.2021.101256. Green open access

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Abstract

In term and near-term neonates with neonatal encephalopathy, therapeutic hypothermia protocols are well established. The current focus is on how to improve outcomes further and the challenge is to find safe and complementary therapies that confer additional protection, regeneration or repair in addition to cooling. Following hypoxia-ischemia, brain injury evolves over three main phases (latent, secondary and tertiary), each with a different brain energy, perfusion, neurochemical and inflammatory milieu. While therapeutic hypothermia has targeted the latent and secondary phase, we now need therapies that cover the continuum of brain injury that spans hours, days, weeks and months after the initial event. Most agents have several therapeutic actions but can be broadly classified under a predominant action (e.g., free radical scavenging, anti-apoptotic, anti-inflammatory, neuroregeneration, and vascular effects). Promising early/secondary phase therapies include Allopurinol, Azithromycin, Exendin-4, Magnesium, Melatonin, Noble gases and Sildenafil. Tertiary phase agents include Erythropoietin, Stem cells and others. We review a selection of promising therapeutic agents on the translational pipeline and suggest a framework for neuroprotection and neurorestoration that targets the evolving injury.

Type: Article
Title: Therapies for neonatal encephalopathy: Targeting the latent, secondary and tertiary phases of evolving brain injury
Location: Netherlands
Open access status: An open access version is available from UCL Discovery
DOI: 10.1016/j.siny.2021.101256
Publisher version: https://doi.org/10.1016/j.siny.2021.101256
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
Keywords: Neonatal encephalopathy, Neuroprotection, Neurorestoration, Therapeutic hypothermia
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL EGA Institute for Womens Health
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL EGA Institute for Womens Health > Neonatology
URI: https://discovery.ucl.ac.uk/id/eprint/10131235
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