Pathophysiology of Perinatal Hypoxic-Ischemic Encephalopathy – Biomarkers, Animal Models and Treatment Perspectives

Abstract

Hypoxic-ischemic encephalopathy (HIE) is one of the leading pediatric neurological conditions causing long-term disabilities and socio-economical burdens. Nearly 20-50 % of asphyxiated newborns with HIE die within the newborn period and another third will develop severe health consequences and permanent handicaps. HIE is the result of severe systemic oxygen deprivation and reduced cerebral blood flow, commonly occurring in full-term infants. Hypoxic-ischemic changes trigger several molecular and cellular processes leading to cell death and inflammation. Generated reactive oxygen species attack surrounding cellular components resulting in functional deficits and mitochondrial dysfunction. The aim of the present paper is to review present knowledge about the pathophysiology of perinatal hypoxic-ischemic encephalopathy, especially with respect to novel treatment strategies and biomarkers that might enhance early detection of this disorder and thus improve the general outcome of patients.

Alterations in inter‐alpha inhibitor protein expression after hypoxic‐ischemic brain injury in neonatal rats

“…Neuroinflammation is increasingly recognized as an important factor in the normal development of the brain Schwarz, 2009, 2012;Schafer and Stevens, 2015) and is a major contributor to the evolution of HI related brain injury (Ferriero, 2004;Lai et al, 2017;Riljak et al, 2016). On another hand, the immune system also participates in CNS repair processes (Vidale et al, 2017;Wattananit et al, 2016).…”

“…Post-ischemic neuroinflammation is a key pathophysiological factor in the evolution of HI-related brain injury (Ferriero, 2004;Hagberg et al, 2015;Lai et al, 2017;Riljak et al, 2016;Rocha-Ferreira and Hristova, 2016). The first phase of HI injury lasts minutes to hours after the initial insult and is marked by oxidative stress and depletion of energy stores.…”

Neuroprotective effect of licochalcone A against oxygen‐glucose deprivation/reperfusion in rat primary cortical neurons by attenuating oxidative stress injury and inflammatory response via the SIRT1/Nrf2 pathway

“…Perinatal hypoxic‐ischemic encephalopathy (HIE) is currently one of the leading causes of neonatal mortality and long‐term neurodevelopmental disability in children, despite the enormous improvements in perinatal care . HIE in the newborn often results from a hypoxic event and subsequent insufficient cerebral blood flow to the brain, leading to millions of neonatal death or long‐term disabilities every year .…”

Ivabradine does not Impair Anxiety-Like Behavior and Memory in Both Healthy and L-NAME-Induced Hypertensive Rats

“…Especially the prominent proteosynthetic and proliferative effects of L-NAME administration in the brain, reflected by increased concentrations of ribonucleic and deoxyribonucleic acids in the brain tissue (Bernatova et al 1999), suggest the potential of behavioral changes in this model. Second, in addition to hemodynamic changes, prominent neurohumoral alterations (Simko and Simko 2000, Sestakova et al 2013, Riljak et al 2016 as a result of endothelial dysfunction-induced vasoconstriction of the renal artery and concomitant renin-angiotensin-aldosterone system activation, may contribute to structural and functional changes of organs and potential behavioral alterations; whereas aldosterone seems to play an important or even dominant role (Simko et al 2018). Third, we have quite a large experience with the testing of the potential protective effect of various drugs on the cardiovascular system in the L-NAMEmodel, such as captopril (Pechanova et al 1997, Bernatova 2000), spironolactone (Simko et al 2007), L-arginine (Simko et al 2005), simvastatin (Simko et al 2004) and melatonin (Paulis et al 2009.…”