Traumatic brain injury leads to increased expression of peripheral-type benzodiazepine receptors, neuronal death, and activation of astrocytes and microglia in rat thalamus

Vemuganti L. Raghavendra Rao, Aclan Dogan, Kellie K. Bowen, Robert J. Dempsey

Research output: Contribution to journalArticle

137 Scopus citations

Abstract

In mammalian CNS, the peripheral-type benzodiazepine receptor (PTBR) is localized on the outer mitochondrial membrane within the astrocytes and microglia. PTBR transports cholesterol to the site of neurosteroid biosynthesis. Several neurodegenerative disorders were reported to be associated with increased densities of PTBR. In the present study, we evaluated the changes in the PTBR density and gene expression in the brains of rats as a function of time (6 h to 14 days) after traumatic brain injury (TBI). Sham-operated rats served as control. Between 3 and 14 days after TBI, there was a significant increased in the binding of PTBR antagonist [3H]PK11195 (by 106 to 185%, P < 0.01, as assessed by quantitative autoradiography and in vitro filtration binding) and PTBR mRNA expression (by 2- to 3.4-fold, P < 0.01, as assessed by RT-PCR) in the ipsilateral thalamus. At 14 days after the injury, the neuronal number decreased significantly (by 85 to 90%, P < 0.01) in the ipsilateral thalamus. At the same time point, the ipsilateral thalamus also showed increased numbers of the glial fibrillary acidic protein positive cells (astrocytes, by ~3.5-fold) and the ED-1 positive cells (microglia/macrophages, by ~36-fold), the two cell types known to be associated with PTBR. Increased PTBR expression following TBI seems to be associated with microglia/macrophages than astrocytes as PTBR density at different periods after TBI correlated better with the number of ED-1 positive cells (r2 = 0.95) than the GFAP positive cells (r2 = 0.56). TBI-induced increased PTBR expression is possibly an adaptive response to cellular injury and may play a role in the pathophysiology of TBI. (C) 2000 Academic Press.

Original languageEnglish (US)
Pages (from-to)102-114
Number of pages13
JournalExperimental Neurology
Volume161
Issue number1
DOIs
StatePublished - Jan 2000
Externally publishedYes

Keywords

  • Astrocytes
  • Microglia
  • PK11195
  • Peripheral-type benzodiazepine receptor
  • Quantitative autoradiography
  • Traumatic brain injury
  • mRNA

ASJC Scopus subject areas

  • Neurology
  • Developmental Neuroscience

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