Increase of insulin-like growth factor (IGF)-1, IGF binding protein-2 and -4 mRNAs following cerebral contusion.
The insulin-like growth factor (IGF) system has a role in repair following hypoxic-ischemic injury in many tissues including the brain. To study the involvement of the IGF system following head trauma, we used a rat contusion model, which produces a focal lesion of the cerebral cortex. Molecules in the IGF system were analyzed using in situ hybridization at different times following impact. We observed a dramatic up-regulation of insulin-like growth factor binding protein-2 (IGFBP-2) mRNA in cortical areas adjacent to the injury 24 h after impact, with a peak 10-fold increase engaging most of the ipsilateral cortex 2 and 3 days post-contusion. Seven days after the contusion, IGFBP-2 expression was only moderately up-regulated and again concentrated around the injury. IGFBP-4 mRNA levels increased 4-fold ipsilateral to the site of injury, with retained pattern of cortical expression. IGFBP-3, IGFBP-5 and IGFBP-6 mRNA all displayed distinct expression patterns in the brain but no significant changes were observed following injury. In contrast, IGF-1 mRNA levels were very low prior to contusion, but increased markedly at the site of injury with a peak at day 3. We were unable to detect any changes in the type 1 IGF-receptor or IGF-2 mRNA following contusion. The neuropeptide cholecystokinin (CCK) mRNA was clearly up-regulated following contusion, with an even distribution over the ipsilateral cortex. The expression pattern of molecules in the IGF system post-contusion differs in part to changes observed following hypoxic-ischemia or ischemia alone, perhaps reflecting different regulatory mechanisms depending on the type of injury.
Sandberg Nordqvist
A C
AC
Department of Molecular Medicine, Karolinska Hospital, Stockholm, Sweden.
von Holst
H
H
Holmin
S
S
Sara
V R
VR
Bellander
B M
BM
Schalling
M
M
D000818:Animals; D015415:Biomarkers; D001924:Brain Concussion / Q000378:metabolism*; D002540:Cerebral Cortex / Q000293:injuries; D002766:Cholecystokinin / Q000096:biosynthesis; D004195:Disease Models, Animal; D015870:Gene Expression; D007091:Image Processing, Computer-Assisted; D017403:In Situ Hybridization; D018971:Insulin-Like Growth Factor Binding Protein 2 / Q000235:genetics*; D018974:Insulin-Like Growth Factor Binding Protein 4 / Q000235:genetics*; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D008297:Male; D009419:Nerve Tissue Proteins / Q000235:genetics*; D012333:RNA, Messenger / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley
D015415:Biomarkers; D018971:Insulin-Like Growth Factor Binding Protein 2; D018974:Insulin-Like Growth Factor Binding Protein 4; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D007334:Insulin-Like Growth Factor I; D002766:Cholecystokinin