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Vol. 23, No. 3, 2001
Issue release date: 2001
Dev Neurosci 2001;23:234–247
(DOI:10.1159/000046149)

Hypoxia/Ischemia Depletes the Rat Perinatal Subventricular Zone of Oligodendrocyte Progenitors and Neural Stem Cells

Levison S.W. · Rothstein R.P. · Romanko M.J. · Snyder M.J. · Meyers R.L. · Vannucci S.J.
Department of Neuroscience and Anatomy, Pennsylvania State University, College of Medicine, Hershey, Pa., USA

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Abstract

Cerebral hypoxia/ischemia of the newborn has a frequency of 4/1,000 births and remains a major cause of cerebral palsy, epilepsy, and mental retardation. Despite progress in understanding the pathogenesis of hypoxic-ischemic injury, the data are incomplete regarding the mechanisms leading to permanent brain injury. Here we tested the hypothesis that cerebral hypoxia/ischemia damages stem/progenitor cells in the subventricular zone (SVZ), resulting in a permanent depletion of oligodendrocytes. We used a widely accepted rat model and examined animals at recovery intervals ranging from 4 h to 3 weeks. Within hours after the hypoxic-ischemic insult 20% of the total cells were deleted from the SVZ. The residual damaged cells appeared necrotic. During 48 h of recovery deaths accumulated; however, these later deaths were predominantly apoptotic. Many apoptotic SVZ cells stained with a marker for immature oligodendrocytes. At 3 weeks survival, the SVZ was smaller and markedly less cellular, and it contained less than 1/4 the normal complement of neural stem cells. The corresponding subcortical white matter was dysmyelinated, relatively devoid of oligodendrocytes and enriched in astrocytes. We conclude that neural stem cells and oligodendrocyte progenitors in the SVZ are vulnerable to hypoxia/ischemia. Consequently, the developmental production of oligodendrocytes is compromised and regeneration of damaged white matter oligodendrocytes does not occur resulting in failed regeneration of CNS myelin in periventricular loci. The resulting dysgenesis of the brain that occurs subsequent to perinatal hypoxic/ischemic injury may contribute to the cognitive and motor dysfunction that results from asphyxia of the newborn.



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References

  1. Rothstein RP, Vannucci SJ, Levison SW: Necrotic death in the subependymal zone after hypoxia/ischemia in the newborn rat. Soc Neurosci Abst 1999;25:843.822.
  2. Romanko MJ, Rothstein RP, Vannucci SJ, Meyers RL, Levison SW: Stem/progenitor cells in the rat subependymal zone are vulnerable to hypoxia/ischemia. Soc Neurosci Abst 2000;26:281–288.
  3. Volpe JJ: Neurology of the Newborn, ed3. Philadelphia, Saunders, 1995.
  4. Dobbing J, Sands J: Quantitative growth and development of human brain. Arch Dis Child Fetal Neonat Ed 1973;48:757.
  5. Scheffler B, Horn M, Blumcke I, Laywell ED, Coomes D, Kukekov VG, Steindler DA: Marrow-mindedness: A perspective on neuropoiesis. TINS 1999;22:348–357.
  6. Goldman SA: Adult neurogenesis: From canaries to the clinic. J Neurobiol 1998;36:267–286.
  7. Levison SW, Goldman JE: Multipotential and lineage restricted precursors coexist in the mammalian perinatal subventricular zone. J Neurosci Res 1997;48:83–94.
  8. Young GM, Levison SW: Persistence of multipotential progenitors in the juvenile rat subventricular zone. Dev Neurosci 1996;18:255–265.
  9. Levison SW, Goldman JE: Both oligodendrocytes and astrocytes develop from progenitors in the subventricular zone of postnatal rat forebrain. Neuron 1993;10:201–212.
  10. Levison SW, Chuang C, Abramson BJ, Goldman JE: The migrational patterns and developmental fates of glial precursors in the rat subventricular zone are temporally regulated. Development 1993;119:611–623.
  11. Goldman JE: Lineage, migration, and fate determination of postnatal subventricular zone cells in the mammalian CNS. J Neurooncol 1995;24:61–64.
  12. Vannucci SJ, Seaman LB, Vannucci RC: Effects of hypoxia-ischemia on GLUT1 and GLUT3 glucose transporters in immature rat brain. J Cereb Blood Flow Met 1996;16:77–81.
  13. Rice JE, Vannucci RC, Brierley JB: The influence of immaturity on hypoxic-ischemic brain damage in the rat. Ann Neurol 1981;9:131–141.
  14. Gross CG: Neurogenesis in the adult brain: Death of a dogma. Nature Rev 2000;1:67–73.
  15. Levison SW, Rothstein RP, Brazel CY, Young GM, Albrecht PJ: Selective apoptosis within the rat subependymal zone: A plausible mechanism for determining which lineages develop from neural stem cells. Dev Neurosci 2000;22:106–115.
  16. Levison SW, Ducceschi MH, Young GM, Wood TL: Acute exposure to CNTF in vivo induces multiple components of reactive gliosis. Exp Neurol 1996;141:256–268.

    External Resources

  17. Towfighi J, Mauger D: Temporal evolution of neuronal changes in cerebral hypoxia-ischemia in developing rats: A quantitative light microscopic study. Dev Brain Res 1998;109:169–177.

    External Resources

  18. Gundersen HJ, Bendtsen TF, Korbo L, Marcussen N, Moller A, Nielsen K, Nyengaard JR, Pakkenberg B, Sorensen FB, Vesterby A, et al: Some new, simple and efficient stereological methods and their use in pathological research and diagnosis. APMIS 1988;96:379–394.
  19. Palmer TD, Markakis EA, Willhoite AR, Safar F, Gage FH: Fibroblast growth factor-2 activates a latent neurogenic program in neural stem cells from diverse regions of the adult CNS. J Neurosci 1999;19:8487–8497.
  20. Martin LJ, Al-Abdulla NA, Brambrink AM, Kirsch JR, Sieber FE, Portera-Cailliau C: Neurodegeneration in excitotoxicity, global cerebral ischemia, and target deprivation: A perspective on the contributions of apoptosis and necrosis. Brain Res Bull 1998;46:281–309.

    External Resources

  21. Doetsch F, Garcia-Verdugo JM, Alvarez-Buylla A: Regeneration of a germinal layer in the adult mammalian brain. Proc Natl Acad Sci USA 1999;96:11619–11624.
  22. Morshead CM, Reynolds BA, Craig CG, McBurney MW, Staines WA, Morassutti D, Weiss S, Van der Kooy D: Neural stem cells in the adult mammalian forebrain: A relatively quiescent subpopulation of subependymal cells. Neuron 1994;13:1071–1082.
  23. Gritti A, Frolichsthal-Schoeller P, Galli R, Parata EA, Cova L, Pagano SF, Bjornson CR, Vescovi AL: Epidermal and fibroblast growth factors behave as mitogenic regulators for a single multipotent stem cell-like population from the subventricular region of the adult mouse forebrain. J Neurosci 1999;19:3287–3297.
  24. Cammer W, Zhang H: II. Localization of Pi class glutathione-S-transferase in the forebrains of neonatal and young rats: Evidence for separation of astrocytic and oligodendrocytic lineages. J Comp Neurol 1992;321:40–45.

    External Resources

  25. Mito T, Ando Y, Takeshita K, Takada K, Takashima S: Ultrasonographical and morphological examination of subependymal cystic lesions of maturely born infants. Neuropediatrics 1989;20:211–214.

    External Resources

  26. Kaplan MS: Neurogenesis in the 3-month-old rat visual cortex. J Comp Neurol 1981;195:323–338.
  27. Kaplan MS: Formation and turnover of neurons in young and senescent animals: An electronmicroscopic and morphometric analysis. Ann NY Acad Sci 1985;457:173–192.

    External Resources

  28. Altman J: Autoradiographic investigation of cell proliferation in the brains of rats and cats. Anat Rec 1963;145:573–591.
  29. Altman J, Das GD: Autoradiographic and histological studies of postnatal neurogenesis: A longitudinal investigation of the kinetics, migration and transformation of cells incorporating thymidine in neonate rats, with special reference to postnatal neurogenesis in some brain regions. J Comp Neurol 1966;126:337–390.

    External Resources

  30. Gould E, Reeves AJ, Graziano MS, Gross CG: Neurogenesis in the neocortex of adult primates [see comments]. Science 1999;286:548–552.
  31. Oka A, Belliveau MJ, Rosenberg PA, Volpe JJ: Vulnerability of oligodendroglia to glutamate: Pharmacology, mechanisms, and prevention. J Neurosci 1993;13:1441–1453.
  32. Paterson JA, Privat A, Ling EA, Leblond CP: Investigation of glial cells in semithin sections. III. Transformation of subependymal cells into glial cells as shown by radioautography after 3H-thymidine injection into the lateral ventricle of the brain of young rats. J Comp Neurol 1973;149:83–102.

    External Resources

  33. Zerlin M, Levison SW, Goldman JE: Early stages of dispersion and differentiation of glial progenitors in the postnatal mammalian forebrain. J Neurosci 1995;15:7238–7249.
  34. Zerlin M, Goldman JE: Interactions between glial progenitors and blood vessels during early postnatal corticogenesis: Blood vessel contact represents an early stage of astrocyte differentiation. J Comp Neurol 1997;387:537–546.
  35. Levison SW, Young GM, Goldman JE: Cycling cells in the neocortex preferentially generate oligodendroglia. J Neurosci Res 1999;57:435–447.
  36. Pfrieger FW, Barres BA: Synaptic efficacy enhanced by glial cells in vitro. Science 1997;277:1684–1687.
  37. Levi G, Gallo V, Ciotti MT: Bipotential precursors of putative fibrous astrocytes and oligodendrocytes in rat cerebellar cultures express distinct surface features and ‘neuron-like’ gamma-aminobutyric acid transport. Proc Natl Acad Sci USA 1986;83:1504–1508.

    External Resources

  38. Reynolds R, Herschkowitz N: Uptake of 3H-GABA by oligodendrocytes in dissociated brain cell culture: A combined autoradiographic and immunocytochemical study. Brain Res 1984;322:17–31.
  39. Kettenmann H, Sonnhof U, Schachner M: Exclusive potassium dependence of the membrane potential in cultured mouse oligodendrocytes. J Neurosci 1983;3:500–505.

    External Resources

  40. Sapirstein VS, Strocchi P, Gilbert JM: Properties and function of brain carbonic anhydrase. Ann NY Acad Sci 1984;429:481–493.

    External Resources

  41. Byravan S, Foster LM, Phan T, Verity AN, Campagnoni AT: Murine oligodendroglial cells express nerve growth factor. Proc Natl Acad Sci USA 1994;91:8812–8816.

    External Resources



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