Neuroinflammatory responses after experimental diffuse traumatic brain injury

Brian Joseph Kelley, Jonathan Lifshitz, John Theodore Povlishock

Research output: Contribution to journalArticle

124 Citations (Scopus)

Abstract

Little is known about microglial activation and macrophage localization after diffuse brain injury (DBI). DBI-mediated perisomatic traumatic axonal injury (TAI) was recently identified within the neocortex, hippocampus, and thalamus, providing an opportunity to characterize immune cell responses within diffusely injured brain loci uncomplicated by contusion. By using moderate midline/central fluid percussion injury, microglial/macrophage responses were examined with antibodies targeting immune cell phenotypes and amyloid precursor protein, a marker of TAI. Parallel assessments of blood-brain barrier alterations were also performed. Within 6 to 48 hours postinjury, microglial activation within injured loci was observed, whereas microglia within non-TAI-containing regions maintained a resting phenotype. Microglial activation shared a spatiotemporal relationship with TAI though no clear interactions were observed. By 7 to 28 days postinjury, activated microglia contained myelin debris, yet revealed limited aggregation. Immunophenotypic macrophages were also localized to injured loci. Select macrophages approximated somatic membranes of perisomatically axotomized neurons with evidence of bouton disruption. No causality was established between blood-brain barrier alterations and these inflammatory responses. These findings indicate rapid, yet initially nonspecific, and persistent microglial/macrophage responses to DBI. DBI-mediated inflammatory responses suggest further expansion of traumatic brain injury histopathologic evaluations to identify neuroinflammation indicative of diffuse pathology.

Original languageEnglish (US)
Pages (from-to)989-1001
Number of pages13
JournalJournal of Neuropathology and Experimental Neurology
Volume66
Issue number11
DOIs
StatePublished - Nov 2007
Externally publishedYes

Fingerprint

Macrophages
Wounds and Injuries
Microglia
Blood-Brain Barrier
Percussion
Phenotype
Macrophage Activation
Amyloid beta-Protein Precursor
Contusions
Neocortex
Myelin Sheath
Thalamus
Causality
Hippocampus
Traumatic Brain Injury
Diffuse Brain Injury
Pathology
Neurons
Membranes
Antibodies

Keywords

  • Fluid percussion
  • Macrophage
  • Microglia
  • Rat
  • Traumatic axonal injury

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Neuroscience(all)

Cite this

Neuroinflammatory responses after experimental diffuse traumatic brain injury. / Kelley, Brian Joseph; Lifshitz, Jonathan; Povlishock, John Theodore.

In: Journal of Neuropathology and Experimental Neurology, Vol. 66, No. 11, 11.2007, p. 989-1001.

Research output: Contribution to journalArticle

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