Proper wiring of newborn neurons to control bladder function after complete spinal cord injury

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 rep...

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Bibliographic Details
Published in:Biomaterials 2023-01, Vol.292, p.121919-121919, Article 121919
Main Authors: Hao, Fei, Jia, Fan, Hao, Peng, Duan, Hongmei, Wang, Zijue, Fan, Yubo, Zhao, Wen, Gao, Yudan, Fan, Orion R., Xu, Fuqiang, Yang, Zhaoyang, Sun, Yi E., Li, Xiaoguang
Format: Article
Language:English
Subjects:
Adult endogenous neurogenesis
Animals
Herpesvirus 1, Suid
Humans
Infant, Newborn
Micturition neural circuits
Neurogenic lower urinary tract dysfunction
Neurons
NT3-chitosan
Retrograde transneuronal tracing
Spinal Cord
Spinal Cord Injuries - therapy
Spinal cord injury
Urinary Bladder
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Summary: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.
ISSN:0142-9612
1878-5905
DOI:10.1016/j.biomaterials.2022.121919