Oligodendrocyte degeneration and recovery after focal cerebral ischemia

S. R. McIver, M. Muccigrosso, E. R. Gonzales, J. M. Lee, M. S. Roberts, M. S. Sands, M. P. Goldberg

Research output: Contribution to journalArticle

39 Citations (Scopus)

Abstract

The vulnerability of oligodendrocytes to ischemic injury may contribute to functional loss in diseases of central white matter. Immunocytochemical methods to identify oligodendrocyte injury in experimental models rely on epitope availability, and fail to discriminate structural changes in oligodendrocyte morphology. We previously described the use of a lentiviral vector (LV) carrying enhanced green fluorescent protein (eGFP) under the myelin basic protein (MBP) promoter for selective visualization of oligodendrocyte cell bodies and processes. In this study, we used LV-MBP-eGFP to label oligodendrocytes in rat cerebral white matter prior to transient focal cerebral ischemia, and examined oligodendrocyte injury 24 h, 48 h and 1 week post-reperfusion by quantifying cell survival and assaying the integrity of myelin processes. There was progressive loss of GFP+ oligodendrocytes in ischemic white matter at 24 and 48 h. Surviving GFP+ cells had non-pyknotic nuclear morphology and were terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL)-negative, but there was marked fragmentation of myelin processes as early as 24 h after stroke. One week after stroke, we observed a restoration of GFP+ oligodendrocytes in ischemic white matter, reflected both by cell counts and by structural integrity of myelin processes. Proliferating cells were not the main source of GFP+ oligodendrocytes, as revealed by bromodeoxyuridine (BrdU) incorporation. These observations identify novel transient structural changes in oligodendrocyte cell bodies and myelinating processes, which may have consequences for white matter function after stroke.

Original languageEnglish (US)
Pages (from-to)1364-1375
Number of pages12
JournalNeuroscience
Volume169
Issue number3
DOIs
StatePublished - Sep 2010

Fingerprint

Oligodendroglia
Brain Ischemia
Myelin Sheath
Myelin Basic Protein
Stroke
Wounds and Injuries
DNA Nucleotidylexotransferase
Transient Ischemic Attack
Bromodeoxyuridine
Reperfusion
Epitopes
Cell Survival
Theoretical Models
Cell Count
White Matter

Keywords

  • Ischemia
  • Lentivirus transduction
  • Oligodendrocyte progenitor
  • White matter

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

McIver, S. R., Muccigrosso, M., Gonzales, E. R., Lee, J. M., Roberts, M. S., Sands, M. S., & Goldberg, M. P. (2010). Oligodendrocyte degeneration and recovery after focal cerebral ischemia. Neuroscience, 169(3), 1364-1375. https://doi.org/10.1016/j.neuroscience.2010.04.070

Oligodendrocyte degeneration and recovery after focal cerebral ischemia. / McIver, S. R.; Muccigrosso, M.; Gonzales, E. R.; Lee, J. M.; Roberts, M. S.; Sands, M. S.; Goldberg, M. P.

In: Neuroscience, Vol. 169, No. 3, 09.2010, p. 1364-1375.

Research output: Contribution to journalArticle

McIver, SR, Muccigrosso, M, Gonzales, ER, Lee, JM, Roberts, MS, Sands, MS & Goldberg, MP 2010, 'Oligodendrocyte degeneration and recovery after focal cerebral ischemia', Neuroscience, vol. 169, no. 3, pp. 1364-1375. https://doi.org/10.1016/j.neuroscience.2010.04.070
McIver SR, Muccigrosso M, Gonzales ER, Lee JM, Roberts MS, Sands MS et al. Oligodendrocyte degeneration and recovery after focal cerebral ischemia. Neuroscience. 2010 Sep;169(3):1364-1375. https://doi.org/10.1016/j.neuroscience.2010.04.070
McIver, S. R. ; Muccigrosso, M. ; Gonzales, E. R. ; Lee, J. M. ; Roberts, M. S. ; Sands, M. S. ; Goldberg, M. P. / Oligodendrocyte degeneration and recovery after focal cerebral ischemia. In: Neuroscience. 2010 ; Vol. 169, No. 3. pp. 1364-1375.
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