Beijing Key Laboratory for Biomaterials and Neural Regeneration, School of Engineering Medicine, Beihang University, Beijing, 100191, China.
Guangdong Provincial Key Laboratory of Brain Connectome and Behavior, CAS Key Laboratory of Brain Connectome and Manipulation, The Brain Cognition and Brain Disease Institute (BCBDI), Translational Research Center for the Nervous System (TRCNS), Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences; Shenzhen-Hong Kong Institute of Brain Science-Shenzhen Fundamental Research Institutions, Shenzhen, 518055, China; University of Chinese Academy of Sciences, Beijing, 100049, China.
Biomaterials. 2023 Jan;292:121919. doi: 10.1016/j.biomaterials.2022.121919. Epub 2022 Nov 25.
Activation of endogenous neurogenesis by bioactive materials enables restoration of sensory/motor function after complete spinal cord injury (SCI) via formation of new relay neural circuits. The underlying wiring logic of newborn neurons in adult central nervous system (CNS) is unknown. Here, we report neurotrophin3-loaded chitosan biomaterial substantially recovered bladder function after SCI. Multiple neuro-circuitry tracing technologies using pseudorabies virus (PRV), rabies virus (RV), and anterograde adeno-associated virus (AAV), demonstrated that newborn neurons were integrated into the micturition neural circuits and reconnected higher brain centers and lower spinal cord centers to control voiding, and participated in the restoration of the lower urinary tract function, even in the absence of long-distance axonal regeneration. Opto- and chemo-genetic studies further supported the notion that the supraspinal control of the lower urinary tract function was partially recovered. Our data demonstrated that regenerated relay neurons could be properly integrated into disrupted long-range neural circuits to restore function of adult CNS.
生物活性材料激活内源性神经发生，通过形成新的中继神经回路，使完全性脊髓损伤 (SCI) 后的感觉/运动功能得以恢复。然而，成年中枢神经系统 (CNS) 中新生神经元的潜在连接逻辑尚不清楚。本研究报道了负载神经营养因子 3 的壳聚糖生物材料可显著恢复 SCI 后的膀胱功能。使用伪狂犬病毒 (PRV)、狂犬病病毒 (RV) 和逆行腺相关病毒 (AAV) 的多种神经回路示踪技术表明，新生神经元整合到排尿神经回路中，重新连接大脑高级中枢和脊髓低级中枢以控制排尿，并参与下尿路功能的恢复，即使没有长距离轴突再生。光遗传和化学遗传研究进一步支持了这样的观点，即下尿路功能的中枢神经控制部分得到了恢复。本研究数据表明，再生的中继神经元可以被适当整合到中断的长距离神经回路中，以恢复成年中枢神经系统的功能。
