Oligodendrocyte lineage and subventricular zone response to traumatic axonal injury in the corpus callosum

Genevieve M. Sullivan, Amanda J. Mierzwa, Naruchorn Kijpaisalratana, Haiying Tang, Yong Wang, Sheng Kwei Song, Reed Selwyn, Regina C. Armstrong

Research output: Contribution to journalArticle

47 Scopus citations

Abstract

Traumatic brain injury frequently causes traumatic axonal injury (TAI) in white matter tracts. Experimental TAI in the corpus callosum of adult mice was used to examine the effects on oligodendrocyte lineage cells and myelin in conjunction with neuroimaging. The injury targeted the corpus callosum over the subventricular zone, a source of neural stem/progenitor cells. Traumatic axonal injury was produced in the rostral body of the corpus callosum by impact onto the skull at the bregma. During the first week after injury, magnetic resonance diffusion tensor imaging showed that axial diffusivity decreased in the corpus callosum and that corresponding regions exhibited significant axon damage accompanied by hypertrophic microglia and reactive astrocytes. Oligodendrocyte progenitor proliferation increased in the subventricular zone and corpus callosum. Oligodendrocytes in the corpus callosum shifted toward upregulation of myelin gene transcription. Plp/CreERT:R26IAP reporter mice showed normal reporter labeling of myelin sheaths 0 to 2 days after injury but labeling was increased between 2 and 7 days after injury. Electron microscopy revealed axon degeneration, demyelination, and redundant myelin figures. These findings expand the cell types and responses to white matter injuries that inform diffusion tensor imaging evaluation and identify pivotal white matter changes after TAI that may affect axon vulnerability vs. recovery after brain injury.

Original languageEnglish
Pages (from-to)1106-1125
Number of pages20
JournalJournal of neuropathology and experimental neurology
Volume72
Issue number12
DOIs
StatePublished - Dec 1 2013

Keywords

  • Axonal damage
  • Corpus callosum
  • Diffusion tensor imaging
  • Oligodendrocyte progenitor
  • Redundant myelin
  • Regeneration
  • Traumatic brain injury

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