Jeanne Paz from Gladstone Institutes, University of California, San Francisco at NYU Langone Health

Traumatic brain injury (TBI) is a leading cause of disability in children and adults. TBI affects 69 million people worldwide yearly and can lead to cognitive dysfunction, difficulty with sensory processing, sleep disruption, and epilepsy. Although TBI acutely disrupts the cortex, most TBI-related disabilities reflect secondary injuries that accrue over time. Our work aims to understand where, when, and how secondary injuries develop, which is crucial for preventing or disability following TBI. The thalamus is a likely site of secondary damage because of its reciprocal connections with the cortex. Using a mouse model of mild TBI (mTBI), we found a chronic increase in C1q expression specifically in the corticothalamic system. Increased C1q expression colocalized with neuron loss and chronic inflammation and correlated with disruption in sleep spindles and emergence of epileptic activities. Blocking C1q counteracted these outcomes, suggesting that C1q is a disease modifier in mTBI. The corticothalamic circuit could thus be a new target for treating TBI-related disabilities. Dr. Paz will present the ongoing work in her laboratory that aims to identify the cellular and circuit mechanisms behind complement-mediated neural plasticity after TBI and its role in post-traumatic epileptogenesis.

This seminar is generously supported by the Nussenbaum-Vogelstein Family.