Morphological and genetic activation of microglia after diffuse traumatic brain injury in the rat

T. Cao, T. C. Thomas, J. M. Ziebell, J. R. Pauly, Jonathan Lifshitz

Research output: Contribution to journalArticle

89 Citations (Scopus)

Abstract

Traumatic brain injury (TBI) survivors experience long-term post-traumatic morbidities. In diffuse brain-injured rats, a chronic sensory sensitivity to whisker stimulation models the agitation of TBI survivors and provides anatomical landmarks across the whisker-barrel circuit to evaluate post-traumatic neuropathology. As a consequence of TBI, acute and chronic microglial activation can contribute to degenerative and reparative events underlying post-traumatic morbidity. Here we hypothesize that a temporal sequence of microglial activation states contributes to the circuit pathology responsible for post-traumatic morbidity, and test the hypothesis by examining microglial morphological activation and neuroinflammatory markers for activation states through gene expression and receptor-binding affinity. Adult male, Sprague-Dawley rats were subjected to a single moderate midline fluid percussion injury (FPI) or sham injury. Microglial activation was determined by immunohistochemistry, quantitative real-time PCR and receptor autoradiography in the primary somatosensory barrel field (S1BF) and ventral posterior medial nucleus (VPM) of the thalamus at 7 and 28 days following FPI. Morphological changes indicative of microglial activation, including swollen cell body with thicker, shrunken processes, were evident in S1BF and VPM at 7 and 28. days post-injury. Principally at 7. days post-injury in VPM, general inflammatory gene expression (major histocompatibility complex I, major histocompatibility complex II, translocator protein 18. kDa [TSPO]) is increased above sham level and TSPO gene expression confirmed by receptor autoradiography. Further, CD45, a marker of classical activation, and TGF-βI, an acquired deactivation marker, were elevated significantly above sham at 7. days post-injury. Daily administration of the anti-inflammatory ibuprofen (20. mg/kg, i.p.) significantly reduced the expression of these genes. Evidence for alternative activation (arginase 1) was not observed. Thus, these data demonstrate concomitant classical activation and acquired deactivation phenotypes of microglia in diffuse TBI in the absence of overt contusion or cavitation. Anti-inflammatory treatment may further alleviate the neuropathological burden of post-traumatic inflammation.

Original languageEnglish (US)
Pages (from-to)65-75
Number of pages11
JournalNeuroscience
Volume225
DOIs
StatePublished - Dec 6 2012
Externally publishedYes

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Microglia
Ventral Thalamic Nuclei
Wounds and Injuries
Percussion
Gene Expression
Vibrissae
Major Histocompatibility Complex
Morbidity
Autoradiography
Survivors
Anti-Inflammatory Agents
Posterior Thalamic Nuclei
Arginase
Contusions
Ibuprofen
Sprague Dawley Rats
Traumatic Brain Injury
Diffuse Brain Injury
Real-Time Polymerase Chain Reaction
Immunohistochemistry

Keywords

  • Alternate activation
  • Anti-inflammatory
  • Classical activation
  • Neuroplasticity

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Morphological and genetic activation of microglia after diffuse traumatic brain injury in the rat. / Cao, T.; Thomas, T. C.; Ziebell, J. M.; Pauly, J. R.; Lifshitz, Jonathan.

In: Neuroscience, Vol. 225, 06.12.2012, p. 65-75.

Research output: Contribution to journalArticle

Cao, T. ; Thomas, T. C. ; Ziebell, J. M. ; Pauly, J. R. ; Lifshitz, Jonathan. / Morphological and genetic activation of microglia after diffuse traumatic brain injury in the rat. In: Neuroscience. 2012 ; Vol. 225. pp. 65-75.
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