Deconstruction and Control of Neural Circuits in Posttraumatic Epilepsy

We pinpointed the hyperexcitable hot spots in the brain responsible for epileptic activities after TBI. These are located in the anterior portion of the injured neocortex in the S1 somatosensory cortex and in the functionally connected somatosensory portion of the thalamus. We found two anatomical and physiological biomarkers of the hot spots 1 a massive upregulation of the C1q molecule, and 2 a reduced synaptic inhibition in these hot spots. These discoveries we made during the first funded year of the award pinpoint the neural circuits that we can now target to test two treatments in parallel. One treatment will consist in blocking the C1q effects by using the anti-C1q ANX005 drug and the second treatment will consist in enhancing synaptic inhibition by human stem cell transplants in the hot spots. We showed the feasibility of these two approaches and are starting to perform chronic recordings to determine the disease-modifying efficacy of the treatments. The results we will obtain during the next two years may lead to two treatments for preventing andor treating the post-traumatic epilepsy after TBI. The long-term impact of this work will be to prevent, control, and cure post-traumatic epilepsy with no side effects, in contrast with the systemic treatment currently provided by anticonvulsants