IGF-I Promotes the Development of Epilepsy through Activation of Akt-mTOR Cascade

Traumatic brain injury (TBI) is a major risk factor for the development of epilepsy, or epileptogenesis. Approximately 1.5 million people in the United States sustain a TBI annually. Insulin-like Growth Factor-I (IGF-I) is found in the cerebrospinal fluid of healthy individuals, and following head injury, IGF-I levels are elevated in the brain tissue. Akt-mTOR and MAPK are downstream targets of IGF-I signaling that are activated after brain injury. However, both brain injury and mTOR are linked to epilepsy, raising the possibility that IGF-I may be epileptogenic. Here, we considered the role of IGF-1 in development of epilepsy after TBI using controlled cortical impact (CCI) in vivo model of brain trauma and organotypic hippocampal cultures in vitro model of epileptogenesis. We found that IGF-I signaling activated the Akt-mTOR pathway after brain injury, and contributed to epileptogenesis.Modulation of the IGF-I-Akt-mTOR signaling may form the basis of new antiepileptic treatments.https://preserve.lehigh.edu/undergrad-scholarship-freed-posters/1000/thumbnail.jp