Neuropediatrics 2022; 53(06): 402-417
DOI: 10.1055/s-0042-1755235
Review Article

Neonatal Hypoxic–Ischemic Encephalopathy: Perspectives of Neuroprotective and Neuroregenerative Treatments

1   Departamento de Fisiología y Farmacología, Laboratorio de Neurofisiología, Centro de Ciencias Básicas, Universidad Autónoma de Aguascalientes, Aguascalientes, México
Denisse Calderón-Vallejo
1   Departamento de Fisiología y Farmacología, Laboratorio de Neurofisiología, Centro de Ciencias Básicas, Universidad Autónoma de Aguascalientes, Aguascalientes, México
2   Departamento de Morfología, Centro de Ciencias Básicas, Universidad Autónoma de Aguascalientes, Aguascalientes, México
J. Luis Quintanar
1   Departamento de Fisiología y Farmacología, Laboratorio de Neurofisiología, Centro de Ciencias Básicas, Universidad Autónoma de Aguascalientes, Aguascalientes, México
› Author Affiliations
Funding This research did not receive any grant from funding agencies in the public, commercial, or not-for-profit sectors.


Hypoxic–ischemic encephalopathy (HIE) is a serious condition that could have deleterious neurological outcomes, such as cerebral palsy, neuromotor disability, developmental disability, epilepsy, and sensitive or cognitive problems, and increase the risk of death in severe cases. Once HIE occurs, molecular cascades are triggered favoring the oxidative stress, excitotoxicity, and inflammation damage that promote cell death via apoptosis or necrosis. Currently, the therapeutic hypothermia is the standard of care in HIE; however, it has a small window of action and only can be used in children of more than 36 gestational weeks; for this reason, it is very important to develop new therapies to prevent the progression of the hypoxic–ischemic injury or to develop neuroregenerative therapies in severe HIE cases. The objective of this revision is to describe the emerging treatments for HIE, either preventing cell death for oxidative stress, excitotoxicity, or exacerbated inflammation, as well as describing a new therapeutic approach for neuroregeneration, such as mesenchymal stem cells, brain-derived neurotrophic factor, and gonadotropin realizing hormone agonists.

Author Contributions

All authors have participated in drafting this manuscript and have approved the final version submitted for publication.


All figures were created with

Publication History

Received: 24 January 2022

Accepted: 21 June 2022

Article published online:
28 August 2022

© 2022. Thieme. All rights reserved.

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

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