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bioRxiv · 10.1101/2020.05.29.120220

Complement factor C1q mediates chronic neuron loss and inflammation post-brain injury

Holden, S. S.·Aboubakr, O.·Higashikubo, B.·Cho, F. S.·Chang, A. H.·Morningstar, A.·Mathur, V.·Kuhn, L. J.·Suri, P.·Sankaranarayanan, S.·Andrews-Zwilling, Y.·Aronica, E.·Yednock, T.·Paz, J. T.
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Abstract

While 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 cortical injury that does not directly damage subcortical structures, we found a chronic increase in C1q expression specifically in the corticothalamic circuit. Increased C1q expression co-localized with neuron loss and chronic inflammation, and correlated with altered cortical rhythms. Blocking C1q counteracted most of these outcomes, suggesting that C1q is a disease modifier in TBI. Since the corticothalamic circuit is important for sensory processing, attention, cognition, and sleep, all of which can be impaired by TBI, this circuit could be a new target for treating TBI-related disabilities.

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Holden, S. S., Aboubakr, O., Higashikubo, B., Cho, F. S., Chang, A. H., Morningstar, A., Mathur, V., Kuhn, L. J., Suri, P., Sankaranarayanan, S., Andrews-Zwilling, Y., Aronica, E., Yednock, T., Paz, J. T.. 2020-05-31. Complement factor C1q mediates chronic neuron loss and inflammation post-brain injury. https://doi.org/10.1101/2020.05.29.120220

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