Complement factor C1q mediates sleep spindle loss and epileptic spikes after mild brain injury

Although traumatic brain injury (TBI) acutely disrupts the cortex, most TBI-related disabilities reflect secondary injuries that accrue over time. 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. Single-nucleus RNA sequencing demonstrated that microglia are a source of thalamic C1q. The corticothalamic circuit could thus be a new target for treating TBI-related disabilities.

Automated summary

Traumatic brain injury (TBI) can acutely damage the cortex, but most disabilities associated with TBI are due to secondary injuries that accumulate over time, with the thalamus potentially being a key site. Research in a mouse model of mild TBI (mTBI) revealed chronic elevation of C1q in the corticothalamic system, correlating with neuron loss, chronic inflammation, disrupted sleep spindles, and emergence of epileptic activities. Blocking C1q may counteract these effects, suggesting it as a potential disease modifier in mTBI, with microglia identified as a source of thalamic C1q. Targeting the corticothalamic circuit could offer new avenues for treating TBI-related disabilities.