TY - JOUR
T1 - Traumatic brain injury leads to increased expression of peripheral-type benzodiazepine receptors, neuronal death, and activation of astrocytes and microglia in rat thalamus
AU - Raghavendra Rao, Vemuganti L.
AU - Dogan, Aclan
AU - Bowen, Kellie K.
AU - Dempsey, Robert J.
N1 - Funding Information:
This work was funded by grants from the American Heart Association National (to V.L.R.R.), American Heart Association Wisconsin Affiliate (to V.L.R.R.), the University of Wisconsin-Madison Medical School Research Committee (to V.L.R.R.) and the National Institute of Health (to R.J.D.). The authors thank Dr. Kathryn Todd and Ms. Carol Gabel for help in conducting the immunohistochemistry and brain sectioning.
PY - 2000/1
Y1 - 2000/1
N2 - 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.
AB - 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.
KW - Astrocytes
KW - Microglia
KW - PK11195
KW - Peripheral-type benzodiazepine receptor
KW - Quantitative autoradiography
KW - Traumatic brain injury
KW - mRNA
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U2 - 10.1006/exnr.1999.7269
DO - 10.1006/exnr.1999.7269
M3 - Article
C2 - 10683277
AN - SCOPUS:0042213235
SN - 0014-4886
VL - 161
SP - 102
EP - 114
JO - Experimental Neurology
JF - Experimental Neurology
IS - 1
ER -