Prolonged activation of NF-kappaB following traumatic brain injury in rats.
Activation of transcription factor, nuclear factor kappa B (NF-kappaB), has been shown to play a key role in inflammatory response, neuronal survival and signaling. We investigated the regional and temporal distribution of activated NF-kappaB in rats at 1 h, 2 h, 24 h, 48 h, 1 week, 2 weeks, 1 month, 2 months, 6 months, and 1 year following brain injury in rats. Early after trauma (1-2 h), activated NF-kappaB was detected in axons, and subsequently found in the cytoplasm and nucleus of neurons by 24 h and lasting up to 1 week. In addition, by 24 h posttrauma, activated NF-kappaB was detected in microglia/macrophages and astrocytes in injured cortex. Surprisingly, this activation persisted for at least 1 year following injury in the cortex, primarily at the margins of progressively enlarging ventricle. Activated NF-kappaB was also detected in endothelial cells, as early as 1 h, and persisted for up to 1 year. These results suggest that a neuronal response to brain trauma includes the activation of NF-kappaB first in the axon with subsequent translocation to the nucleus. Furthermore, these results demonstrate that remarkably prolonged activation of NF-kappaB in glia is found in the same regions undergoing persistent atrophy, suggesting NF-kappaB activation may play a role in long-term inflammatory processes following brain trauma.
Nonaka
M
M
Department of Neurosurgery, University of Pennsylvania Medical Center, Philadelphia 19104, USA.
Chen
X H
XH
Pierce
J E
JE
Leoni
M J
MJ
McIntosh
T K
TK
Wolf
J A
JA
Smith
D H
DH
D000818:Animals; D001930:Brain Injuries / Q000378:metabolism* / Q000503:physiopathology; D004727:Endothelium / Q000166:cytology / Q000378:metabolism*; D008297:Male; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism*; D009457:Neuroglia / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
D016328:NF-kappa B