Differential acute and chronic responses of tumor necrosis factor-deficient mice to experimental brain injury

Uwe Scherbel, Ramesh Raghupathi, Michio Nakamura, Kathryn E. Saatman, John Q. Trojanowski, Edmund Neugebauer, Michael W. Marino, Tracy K. McIntosh

Research output: Contribution to journalArticlepeer-review

351 Scopus citations

Abstract

The present study evaluated behavioral and bistopathological outcome after controlled cortical impact (CCI) brain injury in mice deficient in tumor necrosis factor [TNF(-/-)] and their wild-type (wt) littermates. Mice were subjected to CCI brain injury [TNF(-/-), n = 10; wt, n = 10] or served as uninjured controls [TNF(-/-),n = 10;wt, n = 10] and were evaluated for deficits in memory retention at 7 days postinjury. Although both brain-injured wt and TNF(-/-) mice exhibited significant memory dysfunction compared to uninjured controls (P < 0.02), the deficits in memory retention in injured TNF(-/-) mice were significantly less severe than in injured wt mice (P < 0.02). A second group of mice was subjected to CCI brain injury [TNF(-/-), n = 20; wt, n = 20] or served as uninjured controls [TNF(-/-), n = 15; wt, n = 15] and were evaluated over a 4-week period for neurological motor function. In the acute posttraumatic period (48 h postinjury), brain-injured TNF(-/-) mice were significantly less impaired than injured wt mice on composite neuroscore (P < 0.001), rotarod (P < 0.05), and beam balance (F < 0.02) tests. However, wt mice recovered from brain injury by 2-3 weeks postinjury, whereas TNF(-/-) mice continued to demonstrate persistent motor deficits up to 4 weeks postinjury. Histopathological analysis at 2 and 4 weeks postinjury revealed that brain-injured TNF(-/-) mice had significantly more cortical tissue loss than wt mice (P < 0.02). Our results suggest that although the presence of TNF in the acute posttraumatic period may be deleterious, this cytokine may play a role in facilitating long-term behavioral recovery and histological repair after brain injury.

Original languageEnglish
Pages (from-to)8721-8726
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume96
Issue number15
DOIs
StatePublished - Jul 20 1999

Keywords

  • Central nervous system trauma
  • Cognition
  • Cytokines
  • Histopathology
  • Neuromotor function

ASJC Scopus subject areas

  • General

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