Perisomatic thalamic axotomy after diffuse traumatic brain injury is associated with atrophy rather than cell death

Jonathan Lifshitz, Brian Joseph Kelley, John Theodore Povlishock

Research output: Contribution to journalArticle

69 Scopus citations

Abstract

Morbidity and mortality associated with traumatic brain injury (TBI) stem from diffuse axonal injury (DAI) throughout subcortical and brainstem white matter and subcortical nuclei. After midline fluid percussion brain injury, DAI in the thalamus includes perisomatic axotomy and resembles human post-traumatic pathology where the degree of morbidity correlates with thalamic damage. After axotomy, acute somatic perturbations resolve and appear compatible with cell survival; however, the long-term fate of neurons in an area with perisomatic axotomy is unknown. From brain-injured and uninjured rats at 1, 7 and 28 days after injury (injury, n = 5/group; sham, n = 4), alternate sections were immunostained for amyloid precursor protein (APP) to detect perisomatic axotomy or Giemsa stained for quantification of neuronal number, neuronal density, regional volume, and neuronal nuclear volume using design-based stereology. One day postinjury, APP-immunoreactive axons were identified consistently within the perisomatic domains of thalamic neurons of the ventral basal complex. Bilateral systematic-random quantification of the ventral basal complex indicated a significant reduction in neuronal density (number per mm, but not number alone) at 1 week after injury, compared with sham and 1 day postinjury. Furthermore, by 1 day and persisting through 1 week after injury, the mean neuronal nuclear volume was atrophied significantly compared with sham. Therefore, diffuse TBI results in early perisomatic axonal injury followed by neuronal atrophy in the ventral basal complex, without gross degeneration. Enduring atrophy in thalamic relays could underlie circuit disruption responsible for post-traumatic morbidity.

Original languageEnglish (US)
Pages (from-to)218-229
Number of pages12
JournalJournal of Neuropathology and Experimental Neurology
Volume66
Issue number3
DOIs
StatePublished - Mar 1 2007
Externally publishedYes

Keywords

  • Disector
  • Fractionator
  • Head injury
  • Nucleator
  • Stereology
  • Thalamus
  • Traumatic brain injury

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Neurology
  • Clinical Neurology
  • Cellular and Molecular Neuroscience

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