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 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.
Department of Neurosurgery, School of Medicine, University of Pennsylvania, Philadelphia PA 19104, USA.
U
U
Scherbel
R
R
Raghupathi
M
M
Nakamura
K E
KE
Saatman
J Q
JQ
Trojanowski
E
E
Neugebauer
M W
MW
Marino
T K
TK
McIntosh
D000818:Animals; D001522:Behavior, Animal; D001921:Brain / Q000473:pathology; D001930:Brain Injuries / Q000235:genetics / Q000503:physiopathology*; D018782:Maze Learning; D008568:Memory; D051379:Mice; D018345:Mice, Knockout; D009043:Motor Activity; D004856:Postural Balance; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000172:deficiency* / Q000235:genetics
D014409:Tumor Necrosis Factor-alpha