1. Mitochondrial dysfunction in perinatal asphyxia: role in pathogenesis and potential therapeutic interventions.
- Author
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Samaiya PK, Krishnamurthy S, and Kumar A
- Subjects
- Animals, Asphyxia Neonatorum etiology, Asphyxia Neonatorum metabolism, Female, Humans, Hypoxia-Ischemia, Brain pathology, Infant, Newborn, Mitochondria metabolism, Oxidative Stress, Pregnancy, Asphyxia Neonatorum pathology, Asphyxia Neonatorum therapy, Hypothermia, Induced methods, Hypoxia-Ischemia, Brain metabolism, Mitochondria pathology, Neuroprotective Agents pharmacology
- Abstract
Perinatal asphyxia (PA)-induced brain injury may present as hypoxic-ischemic encephalopathy in the neonatal period, and long-term sequelae such as spastic motor deficits, intellectual disability, seizure disorders and learning disabilities. The brain injury is secondary to both the hypoxic-ischemic event and oxygenation-reperfusion following resuscitation. Following PA, a time-dependent progression of neuronal insult takes place in terms of transition of cell death from necrosis to apoptosis. This transition is the result of time-dependent progression of pathomechanisms which involve excitotoxicity, oxidative stress, and ultimately mitochondrial dysfunction in developing brain. More precisely mitochondrial respiration is suppressed and calcium signalling is dysregulated. Consequently, Bax-dependent mitochondrial permeabilization occurs leading to release of cytochrome c and activation of caspases leading to transition of cell death in developing brain. The therapeutic window lies within this transition process. At present, therapeutic hypothermia (TH) is the only clinical treatment available for treating moderate as well as severe asphyxia in new-born as it attenuates secondary loss of high-energy phosphates (ATP) (Solevåg et al. in Free Radic Biol Med 142:113-122, 2019; Gunn et al. in Pediatr Res 81:202-209, 2017), improving both short- and long-term outcomes. Mitoprotective therapies can offer a new avenue of intervention alone or in combination with therapeutic hypothermia for babies with birth asphyxia. This review will explore these mitochondrial pathways, and finally will summarize past and current efforts in targeting these pathways after PA, as a means of identifying new avenues of therapeutic intervention., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)
- Published
- 2021
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