TY - JOUR
T1 - Therapies for neonatal encephalopathy
T2 - Targeting the latent, secondary and tertiary phases of evolving brain injury
AU - Newborn Brain Society Guidelines and Publications Committee
AU - Chakkarapani, Aravanan A.
AU - Aly, Hany
AU - Benders, Manon
AU - Cotten, C. Michael
AU - El-Dib, Mohamed
AU - Gressens, Pierre
AU - Hagberg, Henrik
AU - Sabir, Hemmen
AU - Wintermark, Pia
AU - Robertson, Nicola J.
N1 - Funding Information:
As described in detail in the present issue (Gunn et al.), NE evolves over time; key phases of brain damage have been described, largely based on HI animal models [9] and supported by magnetic resonance spectroscopy (MRS) data in human term neonates with NE [10] (Fig. 1).
Publisher Copyright:
© 2021 Elsevier Ltd
Copyright:
Copyright 2021 Elsevier B.V., All rights reserved.
PY - 2021/11/22
Y1 - 2021/11/22
N2 - 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.
AB - 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.
KW - Neonatal encephalopathy
KW - Neuroprotection
KW - Neurorestoration
KW - Therapeutic hypothermia
UR - http://www.scopus.com/inward/record.url?scp=85108271933&partnerID=8YFLogxK
U2 - 10.1016/j.siny.2021.101256
DO - 10.1016/j.siny.2021.101256
M3 - Article
AN - SCOPUS:85108271933
SN - 1744-165X
VL - 26
JO - Seminars in Fetal and Neonatal Medicine
JF - Seminars in Fetal and Neonatal Medicine
IS - 5
M1 - 101256
ER -