Cerebral Ischemia and the Developing Brain

Abstract

HomeStrokeVol. 38, No. 2Cerebral Ischemia and the Developing Brain Free AccessResearch ArticlePDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessResearch ArticlePDF/EPUBCerebral Ischemia and the Developing BrainIntroduction Susan J. Vannucci, PhD Susan J. VannucciSusan J. Vannucci From the Department of Pediatrics and the Institute of Human Nutrition, Columbia University, New York, New York. Search for more papers by this author Originally published1 Feb 2007https://doi.org/10.1161/01.STR.0000247898.71423.ffStroke. 2007;38:723The Princeton Conference has focused almost exclusively on cerebrovascular disease in the mature, or adult, brain. This session at the 25th Princeton Conference was quite unique in that the focus was on cerebral ischemia in the developing brain, ie, in both preterm and term infant. Hypoxic-ischemic injury to the developing brain is a major cause of acute mortality and chronic neurological morbidity in infants and children. Statistics suggest an incidence of systemic asphyxia in 2 to 4/1000 full-term births and an incidence approaching 60% in low birth weight, premature newborns.1,2 Between 20% to 50% of asphyxiated newborns with hypoxic-ischemic encephalopathy die within the newborn period, and up to 25% of the survivors go on to exhibit permanent neuropsychological handicaps, including mental retardation, cerebral palsy, epilepsy or learning disability. Care of the fetus and newborn human infant at risk for developing cerebral hypoxia-ischemia is clearly a high priority in current health care, and an understanding of the pathophysiology of perinatal hypoxic-ischemic brain damage is essential to the design of effective therapeutic interventions.Much of our current understanding of the pathophysiology of hypoxic-ischemic brain damage derives from the vast body of experimental literature on stroke in the adult brain. From these studies, it is now well established that a cerebral hypoxic-ischemic event severe enough to cause cellular energy depletion initiates a cascade of events including early events of acidosis, glutamate excitotoxicity, and generation of reactive oxygen species, followed by prolonged periods of delayed cell death and inflammation.3 To a certain extent this cascade is also characteristic of hypoxic-ischemic damage in the immature brain but with some very notable, and important, differences. Whereas the immature brain has long been considered to be “resistant” to the damaging effects of hypoxia-ischemia, we now appreciate that this is not the case but that hypoxic-ischemic injury in the immature brain is different from that in the adult and actually exhibits periods of heightened sensitivity to injury depending on the developmental stage of the brain at the time of injury. Thus, it must be appreciated that the effects of the cascade of events initiated by hypoxia-ischemia will be determined by what normal developmental processes are occurring in the brain at the time of injury, and what developmental processes occur subsequent to the injury.In this regard, hypoxic-ischemic injury to the preterm brain differs substantially to that in the term brain. Aspects and outcomes of injury along the developmental timeline are presented in this symposium.FootnotesCorrespondence to Susan J. Vannucci, Department of Pediatrics and the Institute of Human Nutrition, Columbia University, 3959 Broadway, CHN 10-24, New York, NY, United States 10032. E-mail [email protected]References1 Volpe JJ. Brain injury in the premature infant–current concepts of pathogenesis and prevention. Biol Neonate. 1992; 62: 231–242.CrossrefMedlineGoogle Scholar2 Vannucci RC. Hypoxic-ischemic encephalopathy. Am J Perinatol. 2000; 17: 113–120.CrossrefMedlineGoogle Scholar3 Dirnagl U, Iadecola C, Moskowitz MA. Pathobiology of ischaemic stroke: an integrated view. Trends Neurosci. 1999; 22: 391–397.CrossrefMedlineGoogle Scholar Previous Back to top Next FiguresReferencesRelatedDetailsCited By Wong R, Abussaud A, Leung J, Xu B, Li F, Huang S, Chen N, Wang G, Feng Z and Sun H (2018) Blockade of the swelling-induced chloride current attenuates the mouse neonatal hypoxic-ischemic brain injury in vivo, Acta Pharmacologica Sinica, 10.1038/aps.2018.1, 39:5, (858-865), Online publication date: 1-May-2018. Sun H and Feng Z (2017) TRPM7 Channels as Potential Therapeutic Targets for Stroke Neuroprotective Therapy for Stroke and Ischemic Disease, 10.1007/978-3-319-45345-3_16, (415-432), . Xu B, Xiao A, Chen W, Turlova E, Liu R, Barszczyk A, Sun C, Liu L, Tymianski M, Feng Z and Sun H (2015) Neuroprotective Effects of a PSD-95 Inhibitor in Neonatal Hypoxic-Ischemic Brain Injury, Molecular Neurobiology, 10.1007/s12035-015-9488-4, 53:9, (5962-5970), Online publication date: 1-Nov-2016. Sun H, Xu B, Chen W, Xiao A, Turlova E, Alibraham A, Barszczyk A, Bae C, Quan Y, Liu B, Pei L, Sun C, Deurloo M and Feng Z (2015) Neuronal KATP channels mediate hypoxic preconditioning and reduce subsequent neonatal hypoxic–ischemic brain injury, Experimental Neurology, 10.1016/j.expneurol.2014.10.003, 263, (161-171), Online publication date: 1-Jan-2015. Alibrahim A, Zhao L, Bae C, Barszczyk A, Lf Sun C, Wang G and Sun H (2012) Neuroprotective effects of volume-regulated anion channel blocker DCPIB on neonatal hypoxic-ischemic injury, Acta Pharmacologica Sinica, 10.1038/aps.2012.148, 34:1, (113-118), Online publication date: 1-Jan-2013. February 2007Vol 38, Issue 2 Advertisement Article InformationMetrics https://doi.org/10.1161/01.STR.0000247898.71423.ff Manuscript receivedJune 27, 2006Manuscript acceptedAugust 6, 2006Originally publishedFebruary 1, 2007 PDF download Advertisement