期刊
JOURNAL OF NEUROTRAUMA
卷 34, 期 21, 页码 3058-3065出版社
MARY ANN LIEBERT, INC
DOI: 10.1089/neu.2017.5045
关键词
crossed-phrenic phenomenon; interneurons; plasticity; respiration; spinal cord injury
资金
- NIH [R01 NS081112, R01 NS095366, P01 NS 055976, 338432]
- Spinal Cord Research Center at Drexel University, College of Medicine
- Lynn Enquist (Princeton University) as part of Virus Center [P40 RR018604]
- NINDS
More than half of all spinal cord injuries (SCIs) occur at the cervical level, often resulting in impaired respiration. Despite this devastating outcome, there is substantial evidence for endogenous neuroplasticity after cervical SCI. Spinal interneurons are widely recognized as being an essential anatomical component of this plasticity by contributing to novel neuronal pathways that can result in functional improvement. The identity of spinal interneurons involved with respiratory plasticity post-SCI, however, has remained largely unknown. Using a transgenic Chx10-eGFP mouse line (Strain 011391-UCD), the present study is the first to demonstrate the recruitment of excitatory interneurons into injured phrenic circuitry after a high cervical SCI. Diaphragm electromyography and anatomical analysis were used to confirm lesion-induced functional deficits and document extent of the lesion, respectively. Transneuronal tracing with pseudorabies virus (PRV) was used to identify interneurons within the phrenic circuitry. There was a robust increase in the number of PRV-labeled V2a interneurons ipsilateral to the C2 hemisection, demonstrating that significant numbers of these excitatory spinal interneurons were anatomically recruited into the phrenic motor pathway two weeks after injury, a time known to correspond with functional phrenic plasticity. Understanding this anatomical spinal plasticity and the neural substrates associated with functional compensation or recovery post-SCI in a controlled, experimental setting may help shed light onto possible cellular therapeutic candidates that can be targeted to enhance spontaneous recovery.
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