Neurosciences Graduate Program, University of California, San Francisco, San Francisco, CA 94158, USA.
Gladstone Institute of Neurological Disease, Gladstone Institutes, San Francisco, CA 94158, USA.
Science. 2021 Sep 10;373(6560):eabj2685. doi: 10.1126/science.abj2685.
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.
尽管创伤性脑损伤 (TBI) 会急性破坏皮质，但大多数与 TBI 相关的残疾反映了随着时间的推移而累积的继发性损伤。丘脑是继发性损伤的可能部位，因为它与皮质有相互连接。使用轻度 TBI (mTBI) 的小鼠模型，我们发现 C1q 的表达在皮质丘脑系统中特异性地慢性增加。C1q 表达的增加与神经元丢失和慢性炎症相一致，并与睡眠纺锤波的中断和癫痫活动的出现相关。阻断 C1q 可逆转这些结果，表明 C1q 是 mTBI 的疾病修饰因子。单细胞 RNA 测序表明，小胶质细胞是丘脑 C1q 的来源。因此，皮质丘脑回路可能成为治疗与 TBI 相关残疾的新靶点。
