Hypoxic-Ischemic Encephalopathy in the Term Infant

Abstract

SynopsisHypoxia-ischemia in the perinatal period is an important cause of cerebral palsy and associated disabilities in children. There has been significant research progress in hypoxic-ischemic encephalopathy over the last two decades and many new molecular mechanisms have been identified. Despite all these advances, therapeutic interventions are still limited. In this review paper, we discuss a number of molecular pathways involved in hypoxia-ischemia, and potential therapeutic targets. KeywordsHypoxia ischemia; neonatal encephalopathy; apoptosis; oxidative stress; hypothermia IntroductionHypoxia-ischemia in the perinatal period is an important cause of cerebral palsy and associated disabilities in children. Cerebral palsy is one of the most costly neurologic disabilities because of its frequency (2/1000 births) and persistence over the life span. 1 In the term infant, the most common mechanism of hypoxic injury is intrauterine asphyxia brought on by circulatory problems, such as clotting of placental arteries, placental abruption, or inflammatory processes. 2 These result in perinatal depression leading to diminished exchange of oxygen and carbon dioxide and severe lactic acidosis. 2 A recent study by Graham et al showed that the incidence of neonatal neurologic morbidity and mortality for term infants born with cord pH < 7.0 is approximately 25%. 3 Reduced cardiac output in the setting of hypoxia is referred to as hypoxiaischemia (HI). 4 If an episode of HI is severe enough to damage the brain, it leads within 12 to 36 hours to a neonatal encephalopathy known as hypoxic-ischemic encephalopathy (HIE). 5 This clinical syndrome includes seizures, epileptic activity on electroencephalogram (EEG), Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. NIH Public Access Author ManuscriptClin Perinatol. Author manuscript; available in PMC 2010 December 1. Published in final edited form as:Clin Perinatol. 2009 December ; 36(4): 835-vii. doi:10.1016/j.clp.2009.011. NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript hypotonia, poor feeding, and a depressed level of consciousness that typically lasts from 7-14 days. 6 Pathology studies of term neonates who sustained a profound hypoxic-ischemic event show relative cortical sparing and deep gray matter injury particularly involving hippocampi, lateral geniculate nuclei, putamen, ventrolateral thalami, and dorsal mesencephalon. 7 There is no effective pharmacologic therapy, although hypothermia has shown promise in several clinical trials. 8,9 Magnetic resonance imaging (MRI) has markedly improved the understanding ...

Feature Extraction and Classification to Diagnose Hypoxic-Ischemic Encephalopathy Patients by Using Susceptibility-Weighted MRI Images

“…Hypoxic-ischemic encephalopathy (HIE) is a type of neurological impairment or injury in infants caused by low oxygen during the perinatal period, and it is a long-term, frequent, severe disease [1][2]. In the developed world, HIE is a common illness affecting approximately 1.5-2 patients per 1,000 new-born infants per year [3].…”

Recent Information on the Pathogenesis and Treatment of Hypoxic-Ischemic Brain Lesions in Newborns

“…Традиционно основные лечебные тактики в острый период гипоксически-ишемических перинатальных поражений головного мозга (ГИППГМ) предусма-тривают медикаментозное поддержание сердечно-легочных функций и противосудорожную защиту [1]. Послед ние достижения в раскрытии патофизиологи-ческих механизмов непосредственно ГИП дают опору для поиска и внедрения новых лечебных технологий.…”

“…Механизмы этого повреждения связывают с глиозом, активаци-ей рецептора стойкого воспаления и эпигенетически-ми изменениями. С целью более детальной проработ-ки терапевтических мишеней ученые концентрируются на отдельных звеньях представленных выше механиз-мов -некрозе и апоптозе, глутаматной эксайтотоксич-ности, окислительном стрессе, воспалении, ангио-и ней-рогенезе [1,5].…”

“…Однако, высокая нейрональная активность, с одной сто-роны, и уязвимость для эксайтотоксичности -с дру-гой -созда ют парадоксальную ситуацию: незрелый мозг способен дольше выдерживать ситуацию низкого энер-гообеспечения по сравнению со взрослым (за счет высо-кой возбудимости глутаматных рецепторов), но, с другой стороны, при достижении определенного критического порога энергодефицита нейрональная деструкция раз-вивается гораздо сильней и за счет разворачивания эк-сайтотоксичности -необратимо [1]. Это важный нюанс, объясняющий выраженность органических дефектов и низкую эффективность лечебных мероприятий в случае тяжелого эпизода гипоксии-ишемии, а также отсутствие подобных драматических эффектов на развивающийся мозг длительных, но невыраженных экспозиций стрес-соров (недостаточность питания, подострая гипоксия и т.…”

Therapeutic Hypothermia for Management of Neonatal Asphyxia: What Nurses Need to Know

“…Cell edema and lysis follow the influx of sodium and water. 5 Elevated levels of glutamate and intracellular calcium cause further cell damage by breaking down cell proteins and hydrolyzing lipids in Nevart Chirinian, BSc, MSc, NP (BC) Nancy Mann, RN …”