Concomitant upregulation of nuclear factor-kB activity, proinflammatory cytokines and ICAM-1 in the injured brain after cortical contusion trauma in a rat model.
BACKGROUND
Nuclear factor kappa B (NF-kB), proinflammatory cytokines and intercellular adhesion molecule 1 (ICAM-1) are frequently upregulated in the injured brain after traumatic brain injury (TBI). However, the temporal pattern of upregulation is not well defined.


OBJECTIVE
The current study was undertaken to investigate the temporal profile of the expression of NF-kB, proinflammatory cytokines and ICAM-1 in the injured brain after cortical contusion trauma of the rat brain.


METHODS
A rat model of cortical contusion was produced by a free-falling weight on the exposed dura of right parietal lobe. The rats were randomly divided into control group and TBI groups at hours 3, 12, 24 and 72, and on day 7.


METHODS
NF-kB binding activity in the surrounding brain of injured area was studied by electrophoretic mobility shift assay (EMSA). The levels of TNF-alpha and IL-6 were detected using ELISA and ICAM-1 expression studied by immunohistochemistry.


METHODS
The data were analyzed by one-way ANOVA followed by Student-Newman-Keuls post hoc test. Relation between variables was analyzed using bivariate correlation with two-tailed test.


RESULTS
Compared with that of control group, NF-kB binding activity in the injured brain was significantly increased through 12 h and 7 days postinjury, with the maximum at 72 h. The concentrations of TNF-alpha and IL-6 in the injured brain were significantly increased from 3 h to 7 days and maximal at 24 h postinjury. The number of ICAM-1 immunostained microvessels was significantly increased in the injured brain from 24 h to 7 days postinjury, with its peak at 72 h. Concomitant upregulation of TNF-alpha, IL-6, ICAM-1 and the cytokine mediators NF-kB in the injured brain was observed in the injured brain after cortical contusion, and there was a highly positive relation among these variables.


CONCLUSIONS
Cortical contusion trauma could induce a concomitant and persistent upregulation of NF-kB binding activity, TNF-alpha, IL-6 and ICAM-1 in the injured rat brain which might play a central role in the injury-induced immune response of brain.
Hang
Chun Hua
CH
Department of Neurosurgery, Jinling Hospital, Clinical School of Medicine, Nanjing University, China. hang1965@public1.ptt.js.cn
Shi
Ji-Xin
JX
Li
Jie-Shou
JS
Wu
Wei
W
Yin
Hong Xia
HX
D000818:Animals; D001930:Brain Injuries / Q000276:immunology / Q000503:physiopathology*; D016207:Cytokines / Q000378:metabolism*; D004195:Disease Models, Animal; D007150:Immunohistochemistry; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism*; D008297:Male; D016328:NF-kappa B / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar
D016207:Cytokines; D016328:NF-kappa B; D018799:Intercellular Adhesion Molecule-1