Abstract
The role of tumor necrosis factor (TNF) and its receptors after traumatic brain injury (TBI) remains unclear. We evaluated the effects of genetic deletion of either p55 or p75 TNF receptor on neurobehavioral outcome, histopathology, DNA damage and apoptosis-related cell death/survival gene expression (bcl-2/bax), and microglia/macrophage (M/M) activation in wild-type (WT) and knockout mice after TBI. Injured p55 (-/-) mice showed a significant attenuation while p75 (-/-) mice showed a significant worsening of sensorimotor deficits compared with WT mice over 4 weeks postinjury. At the same time point, contusion volume in p55 (-/-) mice (11.1±3.3 mm 3) was significantly reduced compared with WT (19.7±3.4 mm 3) and p75 (-/-) mice (20.9±3.2 mm 3). At 4 hours postinjury, bcl-2/bax ratio mRNA expression was increased in p55 (-/-) compared with p75 (-/-) mice and was associated with reduced DNA damage terminal deoxynucleotidyl transferaseYmediated dUTP nick end labeling (TUNEL-positivity), reduced CD11b expression and increased Ym1 expression at 24 hours postinjury in p55 (-/-) compared with p75 (-/-) mice, indicative of a protective M/M response. These data suggest that TNF may exacerbate neurobehavioral deficits and tissue damage via p55 TNF receptor whose inhibition may represent a specific therapeutic target after TBI.
| Original language | English |
|---|---|
| Pages (from-to) | 1182-1189 |
| Number of pages | 8 |
| Journal | Journal of Cerebral Blood Flow and Metabolism |
| Volume | 33 |
| Issue number | 8 |
| DOIs | |
| Publication status | Published - Aug 2013 |
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Keywords
- apoptosis
- inflammation
- microglia
- pathophysiology
- traumatic brain injury
- tumor necrosis factor
ASJC Scopus subject areas
- Cardiology and Cardiovascular Medicine
- Clinical Neurology
- Neurology
Cite this
Tumor necrosis factor in traumatic brain injury : Effects of genetic deletion of p55 or p75 receptor. / Longhi, Luca; Perego, Carlo; Ortolano, Fabrizio; Aresi, Silvia; Fumagalli, Stefano; Zanier, Elisa R.; Stocchetti, Nino; De Simoni, Maria Grazia.
In: Journal of Cerebral Blood Flow and Metabolism, Vol. 33, No. 8, 08.2013, p. 1182-1189.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Tumor necrosis factor in traumatic brain injury
T2 - Effects of genetic deletion of p55 or p75 receptor
AU - Longhi, Luca
AU - Perego, Carlo
AU - Ortolano, Fabrizio
AU - Aresi, Silvia
AU - Fumagalli, Stefano
AU - Zanier, Elisa R.
AU - Stocchetti, Nino
AU - De Simoni, Maria Grazia
PY - 2013/8
Y1 - 2013/8
N2 - The role of tumor necrosis factor (TNF) and its receptors after traumatic brain injury (TBI) remains unclear. We evaluated the effects of genetic deletion of either p55 or p75 TNF receptor on neurobehavioral outcome, histopathology, DNA damage and apoptosis-related cell death/survival gene expression (bcl-2/bax), and microglia/macrophage (M/M) activation in wild-type (WT) and knockout mice after TBI. Injured p55 (-/-) mice showed a significant attenuation while p75 (-/-) mice showed a significant worsening of sensorimotor deficits compared with WT mice over 4 weeks postinjury. At the same time point, contusion volume in p55 (-/-) mice (11.1±3.3 mm 3) was significantly reduced compared with WT (19.7±3.4 mm 3) and p75 (-/-) mice (20.9±3.2 mm 3). At 4 hours postinjury, bcl-2/bax ratio mRNA expression was increased in p55 (-/-) compared with p75 (-/-) mice and was associated with reduced DNA damage terminal deoxynucleotidyl transferaseYmediated dUTP nick end labeling (TUNEL-positivity), reduced CD11b expression and increased Ym1 expression at 24 hours postinjury in p55 (-/-) compared with p75 (-/-) mice, indicative of a protective M/M response. These data suggest that TNF may exacerbate neurobehavioral deficits and tissue damage via p55 TNF receptor whose inhibition may represent a specific therapeutic target after TBI.
AB - The role of tumor necrosis factor (TNF) and its receptors after traumatic brain injury (TBI) remains unclear. We evaluated the effects of genetic deletion of either p55 or p75 TNF receptor on neurobehavioral outcome, histopathology, DNA damage and apoptosis-related cell death/survival gene expression (bcl-2/bax), and microglia/macrophage (M/M) activation in wild-type (WT) and knockout mice after TBI. Injured p55 (-/-) mice showed a significant attenuation while p75 (-/-) mice showed a significant worsening of sensorimotor deficits compared with WT mice over 4 weeks postinjury. At the same time point, contusion volume in p55 (-/-) mice (11.1±3.3 mm 3) was significantly reduced compared with WT (19.7±3.4 mm 3) and p75 (-/-) mice (20.9±3.2 mm 3). At 4 hours postinjury, bcl-2/bax ratio mRNA expression was increased in p55 (-/-) compared with p75 (-/-) mice and was associated with reduced DNA damage terminal deoxynucleotidyl transferaseYmediated dUTP nick end labeling (TUNEL-positivity), reduced CD11b expression and increased Ym1 expression at 24 hours postinjury in p55 (-/-) compared with p75 (-/-) mice, indicative of a protective M/M response. These data suggest that TNF may exacerbate neurobehavioral deficits and tissue damage via p55 TNF receptor whose inhibition may represent a specific therapeutic target after TBI.
KW - apoptosis
KW - inflammation
KW - microglia
KW - pathophysiology
KW - traumatic brain injury
KW - tumor necrosis factor
UR - http://www.scopus.com/inward/record.url?scp=84881190695&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84881190695&partnerID=8YFLogxK
U2 - 10.1038/jcbfm.2013.65
DO - 10.1038/jcbfm.2013.65
M3 - Article
VL - 33
SP - 1182
EP - 1189
JO - Journal of Cerebral Blood Flow and Metabolism
JF - Journal of Cerebral Blood Flow and Metabolism
SN - 0271-678X
IS - 8
ER -