After mild traumatic brain injury (TBI), a molecule called complement factor C1q may play a role in the secondary effects of brain injury, such as sleep disruption, epileptic activity, and inflammation, according to a new study in mice.
The findings suggest that genetic or drug-induced manipulations of the complement pathway could improve the outcomes of mild and severe TBI. Traumatic brain injury (TBI) is a leading cause of disability in children and adults affecting nearly 69 million people worldwide each year. Even mild TBI can lead to cognitive and sensory dysfunction, sleep disruption and epilepsy. However, many of these outcomes are caused by indirect secondary injuries that develop as consequences of TBI and can appear months – even years – after the initial impact. Understanding where, when and how these secondary injuries arise is critical for preventing and treating TBI-related disabilities.
Previous work has suggested that a potential mediator of post-TBI disabilities is the complement pathway, which can promote increased inflammation and neurotoxicity near brain injury sites. Using a mouse model of mild TBI, Stephanie Holden and colleagues evaluated the role of complement component 1q (C1q), a mediator of the complement pathway. They found that increased C1q expression was responsible for chronic inflammation and secondary neuronal loss, specifically in the cortico-thalamo-cortical circuit, and that it correlated with the disruption of sleep and the development of epileptic activities in the brain.
What's more, Holden et al. show that blocking C1q expression counteracted these outcomes, findings that suggest that this molecule plays a role in modifying post-TBI disease.
Holden, S.S., et al. (2021) Complement factor C1q mediates sleep spindle loss and epileptic spikes after mild brain injury. Science. doi.org/10.1126/science.abj2685.