Posted November 13, 2015
Note: Bolded hyperlinks will direct you to the investigators' public and technical abstracts, and publications, if applicable.
Dr. Peter Crino (FY05; University of Pennsylvania) identified stem cell markers as well as altered expression of many growth factors, including VEGF, as possible markers for inflammation in human TSC brain lesions. This work has helped to demonstrate the activation of inflammatory pathways in the brain that are characteristic of TSC and the role of mTOR signaling in lesion formation. It is now believed that inflammation may be an important process in the development of refractory seizures.
Dr. Michael Wong (FY11; Washington University in St. Louis) demonstrated that specific inflammatory cytokines and chemokines are abnormally activated during epileptogenesis in a mouse model of TSC. Treatment with an anti-inflammatory drug that inhibited specific cytokine and chemokine expression inhibited pathological abnormalities, decreased seizures, and improved survival in this mouse model. Overall, these findings implicate inflammatory mechanisms in epileptogenesis and provide proof-of-principle that anti-inflammatory treatments targeting these mechanisms may be a rational therapeutic approach for epilepsy and other neurological manifestations of TSC.