Preclinical and mechanistic study of the beneficial effects of M-current increase after a traumatic brain injury

Project: Research

Investigators

  • Fabio Vigil (PI)

Description

In recent publication, we have shown that after a traumatic brain injury (TBI), an increase of K+ M-current with retigabine treatment results in decreased seizures, metabolic stress, inflammation, cell death, and blood-brain barrier breakdown. The first aim of this proposal is to perform in mice the necessary preclinical tests to proceed toward clinical trials. We will use EEG/video recording and IVIS imaging of cell death to test optimum retigabine dose and therapeutic window after a blunt TBI. To compare the efficiency of one or repetitive doses of retigabine treatment, we will test for TBI-induced long-term behavioral impairments. The second aim of this proposal is to probe for mechanistic explanations for the beneficial effects of M-current increase following TBI. We will use in vivo two-photon imaging and slice electrophysiology experiments to study the effects of TBI and RTG treatment, on neuronal activity and on the diameter and permeability of the brain's blood vessels. Our expertise in all the experiments proposed is verified by our previous publications and preliminary results. This is a promising project that could help millions of patients. It has even caught the attention of the media, which led to a few interviews (see Lay summary).
Award amount$135,352.00
Award date01/01/2020
Program typePostdoctoral Fellowship
Award ID20POST35180050
Effective start/end date01/01/202012/31/2021
StatusActive