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

The present study evaluated behavioral and histopathological outcome after controlled cortical impact (CCI) brain injury in mice deficient in tumor ne crosis factor [TNF(-/-)] and their wild-type (wt) littermates. Mice were su bjected to CCI brain injury [TNF(-/-), n = 10; wt, n = 10] or served as uni njured controls [TNF(-/-), n = 10; wt, n = 10] and were evaluated for defic its in memory retention at 7 days postinjury, Although both brain-injured w t and TNF(-/-) mice exhibited significant memory dysfunction compared to un injured controls (P < 0.02), the deficits in memory retention in injured TN F(-/-) mice were significantly less severe than in injured wt mice (P < 0.0 2). 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 functio n. 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) te sts. 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 postinj ury revealed that brain-injured TNF(-/-) mice had significantly more cortic al tissue loss than wt mice (P < 0.02). Our results suggest that although t he presence of TNF in the acute posttraumatic period may be deleterious, th is cytokine may play a role in facilitating long-term behavioral recovery a nd histological repair after brain injury.