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PMID: 10414954 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S.

Exacerbation of damage and altered NF-kappaB activation in mice lacking tumor necrosis factor receptors after traumatic brain injury.

The Journal of neuroscience : the official journal of the Society for Neuroscience ·Vol. 19 ·No. 15 ·1999-08-01 ·Pages 6248-56

Sullivan PG, Bruce-Keller AJ, Rabchevsky AG, Christakos S, Clair DK, Mattson MP, Scheff SW

Abstract

Tumor necrosis factor alpha (TNFalpha) is widely expressed in both neurons and glia and has been shown to be upregulated after traumatic brain injury (TBI). TNFalpha receptor activation results in activation of the transcription factor nuclear factor kappaB (NF-kappaB), which may serve an antiapoptotic role via the induction of target genes manganese superoxide dismutase (MnSOD) and/or calbindin. In the present study, we used a controlled cortical impact model of TBI with pertinent lines of transgenic mice to combine both morphological characterization and molecular analysis to elucidate the role of TNFalpha after TBI. Measurements of both the lesion volume and the blood-brain barrier breach indicated exacerbations in mice rendered genetically deficient in both the p55 and p75 TNFalpha receptors (TNFR-KO) compared with wild-type animals. Additionally, animals genetically altered to overexpress MnSOD showed a significant decrease in lesion volume compared with that of control littermates, whereas no alterations were observed in mice lacking the calcium-binding protein calbindin D28k. Analysis of NF-kappaB activation and relative levels of MnSOD revealed delayed responses in the injured cortex of TNFR-KO animals compared with wild-type animals, implying that endogenous TNFalpha may be neuroprotective after TBI.

MeSH Terms
Animals Blood-Brain Barrier/physiology Brain Injuries/metabolism,pathology Calbindin 1 Calbindins Cerebral Cortex/injuries,metabolism,pathology Female Mice Mice, Knockout/genetics NF-kappa B/physiology Receptors, Tumor Necrosis Factor/deficiency,genetics S100 Calcium Binding Protein G/genetics,metabolism Superoxide Dismutase/metabolism Wounds, Nonpenetrating/metabolism,pathology
Chemicals
Calb1 protein, mouse Calbindin 1 Calbindins NF-kappa B Receptors, Tumor Necrosis Factor S100 Calcium Binding Protein G Superoxide Dismutase
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Sullivan P G
Sanders-Brown Center on Aging, University of Kentucky, Lexington, Kentucky 40536-0230, USA.
Bruce-Keller A J
Rabchevsky A G
Christakos S
Clair D K
Mattson M P
Scheff S W
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Article Info
Journal
The Journal of neuroscience : the official journal of the Society for Neuroscience
Abbr.
J Neurosci
ISSN
0270-6474
Published
1999-08-01
Pages
6248-56
Language
English
Region
United States
NLM ID
8102140
PMCID
PMC6782813
Subset
IM
Grants
NCI NIH HHS · CA59835 · United States
NINDS NIH HHS · NS29001 · United States
NINDS NIH HHS · NS31220 · United States
External Links
PubMed source PMC Full Text View journal details
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