Journal article
Differential acute and chronic responses of tumor necrosis factor-deficient mice to experimental brain injury
Proceedings of the National Academy of Sciences - PNAS, v 96(15), pp 8721-8726
20 Jul 1999
PMID: 10411942
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Abstract
The present study evaluated behavioral and histopathological 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 (
P
< 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.
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Details
- Title
- Differential acute and chronic responses of tumor necrosis factor-deficient mice to experimental brain injury
- Creators
- Uwe Scherbel - Departments ofRamesh Raghupathi - Departments ofMichio Nakamura - Departments ofKathryn E Saatman - Departments ofJohn Q Trojanowski - Departments ofEdmund Neugebauer - Departments ofMichael W Marino - Departments ofTracy K McIntosh - Departments of
- Publication Details
- Proceedings of the National Academy of Sciences - PNAS, v 96(15), pp 8721-8726
- Publisher
- The National Academy of Sciences
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Neurobiology and Anatomy
- Web of Science ID
- WOS:000081589400079
- Other Identifier
- 991014878567404721
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- Collaboration types
- Domestic collaboration
- International collaboration
- Web of Science research areas
- Neurosciences