title: Hypoxic-ischemic injury in the immature brain--key vascular and cellular players.
abstract: Over the past decade, much has been learned about the cellular and molecular mechanisms underlying hypoxic-ischemic (H-I) injury in the preterm human brain. The pathogenesis of H-I brain injury is now understood to be multifactorial and quite complex, depending on (i) the severity, intensity and timing of asphyxia, (ii) selective ischemic vulnerability, (iii) the degree of maturity of the brain, and (iv) the characteristics of the ensuing reoxygenation/reperfusion phase. Each of these factors has differential effects on the distinct cell populations in the brain, with certain specific cell types being particularly vulnerable in the developing brain. In this review, we discuss the role of the blood vessels and the distinct cell populations, which are the mayor constitutive elements of the immature brain, in the pathophysiology of H-I lesion. The presence of fragile and poorly anastomosed blood vessels and the existence of disturbances in the blood-brain barrier alter blood flow, vascular tone and nutrient delivery. Brain cells are sensitive to the overstimulation of neurotransmitter receptors, particularly glutamate receptors, which can provoke excitotoxicity leading to the death of neurons and other cells such as astrocytes and oligodendrocyte progenitors. Microglial activation by means of excitatory amino acids and by leukocyte migration initiates the inflammatory response giving rise to an increase in regional cerebral blood flow and promoting astrocyte and oligodendrocyte injuries. A better understanding of these aspects of H-I injury will contribute to more efficient strategies for the management of the associated damage.
authors.affiliation: Department of Cell Biology and Histology, University of the Basque Country, Leioa, Spain.
authors.forename: A
authors.initials: A
authors.lastname: Alvarez-Díaz
authors.forename: E
authors.initials: E
authors.lastname: Hilario
authors.forename: F Goñi
authors.initials: FG
authors.lastname: de Cerio
authors.forename: A
authors.initials: A
authors.lastname: Valls-i-Soler
authors.forename: F J
authors.initials: FJ
authors.lastname: Alvarez-Díaz
mesh_terms: D001253:Astrocytes / Q000473:pathology / Q000502:physiology; D001812:Blood-Brain Barrier / Q000473:pathology / Q000503:physiopathology; D001921:Brain / Q000098:blood supply* / Q000196:embryology / Q000473:pathology; D002536:Cerebral Arteries / Q000473:pathology / Q000503:physiopathology; D006801:Humans; D020925:Hypoxia-Ischemia, Brain / Q000503:physiopathology*; D007231:Infant, Newborn; D017628:Microglia / Q000473:pathology / Q000502:physiology; D009836:Oligodendroglia / Q000473:pathology / Q000502:physiology