Temporal and regional changes in IGF-1/IGF-1R signaling in the mouse brain after traumatic brain injury.
Although neurotrophic factors such as nerve growth factor, basic fibroblast growth factor, brain-derived neurotrophic factor, and neurotrophin 4/5 are elevated after traumatic brain injury (TBI), little is known about the endogenous response of insulin-like growth factor-1 (IGF-1). We evaluated IGF-1, IGF-1 receptor (IGF-1R), and total and phosphorylated Akt (p-Akt), a known downstream mediator of IGF-1 signaling, using ELISA, Western blotting, and immunohistochemistry at 1, 6, 24, 48, and 72 h following 0.5-mm controlled cortical impact brain injury in adult mice. IGF-1 was transiently upregulated in homogenates of injured cortex at 1 h, and cells with increased IGF-1 immunoreactivity were observed in and around the cortical contusion site up to 48 h. IGF-1R and total Akt levels in cortical homogenates were unchanged, although immunohistochemistry revealed regional changes. In contrast, serine p-Akt levels increased significantly in homogenates at 6 h post-injury. Interestingly, delayed increases in vascular IGF-1R, total Akt, and p-Akt immunostaining were observed in and around the cortical contusion. IGF-1 and its downstream mediators were also upregulated in the subcortical white matter. Our findings indicate that moderate TBI results in a brief induction of IGF-1 and its signaling components in the acute post-traumatic period. This may reflect an attempt at endogenous neuroprotection or repair.
Madathil
Sindhu Kizhakke
SK
Spinal Cord and Brain Injury Research Center, Department of Physiology, University of Kentucky, Lexington, Kentucky 40536-0509, USA.
Evans
Heather N
HN
Saatman
Kathryn E
KE
D000818:Animals; D015153:Blotting, Western; D001921:Brain / Q000378:metabolism* / Q000503:physiopathology; D001930:Brain Injuries / Q000378:metabolism* / Q000503:physiopathology; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D007150:Immunohistochemistry; D007334:Insulin-Like Growth Factor I / Q000032:analysis / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009413:Nerve Fibers, Myelinated / Q000378:metabolism; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D017526:Receptor, IGF Type 1 / Q000032:analysis / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology; D013997:Time Factors; D015854:Up-Regulation / Q000502:physiology
D007334:Insulin-Like Growth Factor I; D017526:Receptor, IGF Type 1; D051057:Proto-Oncogene Proteins c-akt