Gut Microbiome and Posttraumatic Epilepsy: Biomarker and Mechanistic Implications
Abstract
The project examines the role of gut dysbiosis in post-traumatic epilepsy (PTE). Using a rat model of PTE - lateral fluid percussion injury (LFPI), the project tests the hypothesis that natural premorbid variations and/or post-LFPI perturbations of gut microbiome contribute to PTE. The goals Year 1 were to (i) obtain administrative approvals (Task 1); (ii) generate rats with LFPI and sham LFPI (iii) collect samples for, and perform longitudinal analysis of microbiome, blood and brain biomarkers of inflammation, biomarkers of intestinal barrier (IB) and blood-brain barrier (BBB) permeability (iv) gather and analyze data of chronic epilepsy after LFPI; (v) collect microbiome samples for subsequent microbiome transfer to recipients for Aim 2/Task 3 (ii-v - Task 2). According to plan, by the end of Year 1, Task 2 is to be 66 percent completed. By the end of the reporting period, generating of experimental subjects and sample collection is on schedule. Sample processing is behind schedule due to the COVID-19 - related research shutdown. Analysis of samples and specimens processed up to-date shows that after LFPI (i) 1/3 of experimental subjects develop PTE; (ii) there are robust changes in microbiome composition (i.e., dysbiosis); (iii) there is significant increase of plasma inflammatory cytokines, which points to peripheral inflammation; (iv) there are disruptions of intestinal and blood-brain barrier; (v) there is pronounced of microglia activation which points to central inflammation. Overall the results confirm the hypothesis on the dysbiosis-PTE connection.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 2020
- Accession Number
- AD1117420
Entities
People
- Andréy Mazarati
Organizations
- University of California, Los Angeles