Differential acute and chronic responses of tumor necrosis factor-deficient mice to experimental brain injury
AUTOR(ES)
Scherbel, Uwe
FONTE
The National Academy of Sciences
RESUMO
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.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=17583Documentos Relacionados
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