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.