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Pathophysiology of hypoxic–ischemic encephalopathy: a review of the past and a view on the future

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Abstract

Hypoxic–ischemic encephalopathy, also referred as HIE, is a type of brain injury or damage that is caused by a lack of oxygen to the brain during neonatal period. The incidence is approximately 1.5 cases per 1000 live births in developed countries. In low and middle-income countries, the incidence is much higher (10‒20 per 1000 live births). The treatment for neonatal HIE is hypothermia that is only partially effective (not more than 50% of the neonates treated achieve an improved outcome). HIE pathophysiology involves oxidative stress, mitochondrial energy production failure, glutaminergic excitotoxicity, and apoptosis. So, in the last years, many studies have focused on peptides that act somewhere in the pathway activated by severe anoxic injury leading to HIE. This review describes the pathophysiology of perinatal HIE and the mechanisms that could be the target of innovative HIE treatments.

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Abbreviations

AIF:

Apoptosis-inducing factor

BBB:

Blood–brain barrier

BIP:

Bax-inhibiting peptide

ETC:

Electron transport chain

HI:

Hypoxia–ischemia

HIE:

Hypoxic–ischemic encephalopathy

HNSC:

Human neural stem cells

MMPs:

Matrix metalloproteinases

MPTP:

Mitochondrial permeability transition pore

NAD+ :

Nicotinamide adenine dinucleotide

NO:

Nitric oxide

PARP:

Poly(ADP-ribose) polymerase

PDHC:

Pyruvate dehydrogenase complex

ROS:

Reactive oxygen species

SOD:

Superoxide dismutase

TGF-β:

Transforming growth factor beta

TNF-α:

Tumor necrosis factor alpha

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Authors and Affiliations

  1. Department of Morphology, Surgery and Experimental Medicine, Institute of Obstetrics and Gynaecology, University of Ferrara, 44121, Ferrara, Italy

    P. Greco, G. Nencini & G. Bonaccorsi

  2. Department of Women Health, Infancy and Adolescence, AUSL Ravenna, 48121, Ravenna, Italy

    I. Piva

  3. Department of Obstetrics and Gynaecology, Policlinico Hospital of Abano Terme, Padua, Italy

    M. Scioscia

  4. Section of Anesthesia and Intensive Care, Department of Morphology, Surgery and Experimental Medicine, University of Ferrara, 44121, Ferrara, Italy

    C. A. Volta & S. Spadaro

  5. Section of Forensic Medicine, Department of Morphology, Surgery and Experimental Medicine, University of Ferrara, 44121, Ferrara, Italy

    M. Neri

  6. Department of Medical and Surgical Sciences, Institute of Obstetrics and Gynaecology, University of Foggia, 71121, Foggia, Italy

    F. Greco, I. Cocco, F. Sorrentino, F. D’Antonio & L. Nappi

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Greco, P., Nencini, G., Piva, I. et al. Pathophysiology of hypoxic–ischemic encephalopathy: a review of the past and a view on the future. Acta Neurol Belg 120, 277–288 (2020). https://doi.org/10.1007/s13760-020-01308-3

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