Combinatorial Biosignatures of Network Dysfunction to Predict Posttraumatic Epilepsy: Clinical Translation from a Robust Mouse Model
Abstract
Traumatic brain injury (TBI) is a leading cause of mortality and morbidity. Early life-saving treatments have improved survival but optimal development of preventive and therapeutic interventions for late sequelae such as post-traumatic epilepsy (PTE) require additional work. The latent period between the biomechanical insult and epilepsy onset presents a unique window of opportunity for antiepileptogenesis treatments in high-risk patients, and effective early preventive treatments in high PTE risk subgroups could provide substantial clinical benefit. The development of preventive interventions has been hampered however by the limited knowledge of the mechanisms underlying TBI-induced epileptogenesis and by the lack of validated non-invasive biomarkers for identifying patients at-risk for PTE. Using an in vivo mouse model of PTE, we will investigate whether changes in specific pathologic neuronal network leading to epilepsy after TBI, can be detected early post-injury by combining EEG and brain MRI analyses, together with measurements of selected blood neuroinflammatory molecules, autoantibodies and circulating micro(mi)RNAs. The key drivers/ key biosignatures identified in the preclinical model will be subjected to preliminary clinical verification using archived acute, subacute and chronic serum samples from TBI patients with/without PTE.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 2021
- Accession Number
- AD1158155
Entities
People
- Elisa R Zanier
Organizations
- University of Milan