Selective vulnerability of late oligodendrocyte progenitors to hypoxia-ischemia

Stephen Back, Byung Hee Han, Ning Ling Luo, Charlene A. Chricton, Steve Xanthoudakis, John Tam, Kara L. Arvin, David M. Holtzman

Research output: Contribution to journalArticle

575 Citations (Scopus)

Abstract

In the premature infant, hypoxic-ischemic damage to the cerebral white matter [periventricular leukomalacia (PVL)] is a common and leading cause of brain injury that often results in chronic neurologic disability from cerebral palsy. The cellular basis for the propensity of white matter injury to occur in the developing brain and the greater resistance of the adult white matter to similar injury remains unknown. By using a neonatal rat model of hypoxic-ischemic injury, we found that the mechanism of perinatal white matter injury involved maturation-dependent vulnerability in the oligodendroctye (OL) lineage. The timing of appearance of late OL progenitors was the major developmental factor that accounted for the susceptibility of the neonatal white matter to injury. Late OL progenitors were the major OL lineage stage killed by apoptosis, whereas early OL progenitors and more mature OLs were highly resistant. The density of pyknotic late OL progenitors was significantly increased in the ischemic hemisphere (67 ± 31 cells/mm2) versus the control hemisphere (2.2 ± 0.4 cells/mm2; mean ± SEM; p = 0.05), which resulted in the death of 72 ± 6% of this OL stage. Surviving late OL progenitors displayed a reactive response in which an increase in cell density was accompanied by accelerated maturation to a P27/kip1-positive oligodendrocyte. Because we showed recently that late OL progenitors populate human cerebral white matter during the high risk period for PVL (Back et al., 2001), maturation-dependent vulnerability of OL progenitors to hypoxia-ischemia may underlie the selective vulnerability to PVL of the white matter in the premature infant.

Original languageEnglish (US)
Pages (from-to)455-463
Number of pages9
JournalJournal of Neuroscience
Volume22
Issue number2
StatePublished - Jan 15 2002

Fingerprint

Oligodendroglia
Ischemia
Periventricular Leukomalacia
Wounds and Injuries
Premature Infants
Cerebral Palsy
Hypoxia
White Matter
Brain Injuries
Nervous System
Cell Count
Apoptosis
Brain

Keywords

  • Actin
  • Caspase-3
  • Cell lineage
  • Cerebral cortex
  • Cerebral white matter
  • Cytochrome c
  • Development
  • Hypoxia-ischemia
  • Immunohistochemistry
  • Ki-67
  • MIB-5
  • Microglia
  • NG2
  • O1 antibody
  • O4 antibody
  • P27
  • Periventricular leukomalacia
  • Prematurity
  • Progenitor
  • Spectrin

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Back, S., Han, B. H., Luo, N. L., Chricton, C. A., Xanthoudakis, S., Tam, J., ... Holtzman, D. M. (2002). Selective vulnerability of late oligodendrocyte progenitors to hypoxia-ischemia. Journal of Neuroscience, 22(2), 455-463.

Selective vulnerability of late oligodendrocyte progenitors to hypoxia-ischemia. / Back, Stephen; Han, Byung Hee; Luo, Ning Ling; Chricton, Charlene A.; Xanthoudakis, Steve; Tam, John; Arvin, Kara L.; Holtzman, David M.

In: Journal of Neuroscience, Vol. 22, No. 2, 15.01.2002, p. 455-463.

Research output: Contribution to journalArticle

Back, S, Han, BH, Luo, NL, Chricton, CA, Xanthoudakis, S, Tam, J, Arvin, KL & Holtzman, DM 2002, 'Selective vulnerability of late oligodendrocyte progenitors to hypoxia-ischemia', Journal of Neuroscience, vol. 22, no. 2, pp. 455-463.
Back S, Han BH, Luo NL, Chricton CA, Xanthoudakis S, Tam J et al. Selective vulnerability of late oligodendrocyte progenitors to hypoxia-ischemia. Journal of Neuroscience. 2002 Jan 15;22(2):455-463.
Back, Stephen ; Han, Byung Hee ; Luo, Ning Ling ; Chricton, Charlene A. ; Xanthoudakis, Steve ; Tam, John ; Arvin, Kara L. ; Holtzman, David M. / Selective vulnerability of late oligodendrocyte progenitors to hypoxia-ischemia. In: Journal of Neuroscience. 2002 ; Vol. 22, No. 2. pp. 455-463.
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AU - Han, Byung Hee

AU - Luo, Ning Ling

AU - Chricton, Charlene A.

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AU - Tam, John

AU - Arvin, Kara L.

AU - Holtzman, David M.

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AB - In the premature infant, hypoxic-ischemic damage to the cerebral white matter [periventricular leukomalacia (PVL)] is a common and leading cause of brain injury that often results in chronic neurologic disability from cerebral palsy. The cellular basis for the propensity of white matter injury to occur in the developing brain and the greater resistance of the adult white matter to similar injury remains unknown. By using a neonatal rat model of hypoxic-ischemic injury, we found that the mechanism of perinatal white matter injury involved maturation-dependent vulnerability in the oligodendroctye (OL) lineage. The timing of appearance of late OL progenitors was the major developmental factor that accounted for the susceptibility of the neonatal white matter to injury. Late OL progenitors were the major OL lineage stage killed by apoptosis, whereas early OL progenitors and more mature OLs were highly resistant. The density of pyknotic late OL progenitors was significantly increased in the ischemic hemisphere (67 ± 31 cells/mm2) versus the control hemisphere (2.2 ± 0.4 cells/mm2; mean ± SEM; p = 0.05), which resulted in the death of 72 ± 6% of this OL stage. Surviving late OL progenitors displayed a reactive response in which an increase in cell density was accompanied by accelerated maturation to a P27/kip1-positive oligodendrocyte. Because we showed recently that late OL progenitors populate human cerebral white matter during the high risk period for PVL (Back et al., 2001), maturation-dependent vulnerability of OL progenitors to hypoxia-ischemia may underlie the selective vulnerability to PVL of the white matter in the premature infant.

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KW - O4 antibody

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KW - Prematurity

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