ArticlePloS one2013
Targeted delivery of TrkB receptor to phrenic motoneurons enhances functional recovery of rhythmic phrenic activity after cervical spinal hemisection.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 59 papers.
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Who cites it
59 citing papers in PubMed, 75 citations in OpenAlex.
- Motor Neuron Size-Dependent Differences in mRNA Expression of Tropomyosin-Related Kinase Receptor B in Adult Rats.Journal of neurochemistry · 2026Article
- Labeling phrenic afferents with intrapleural AAV-PHP.S.Journal of neuroscience methods · 2025Article
- An update on spinal cord injury and diaphragm neuromotor control.Expert review of respiratory medicine · 2025Review
- Article
- Review
- BDNF-TrkB Signaling Pathway in Spinal Cord Injury: Insights and Implications.Molecular neurobiology · 2025Review
- Assessing Functional Recovery of Eupneic Diaphragm Activity Following Unilateral Cervical Spinal Cord Injury in Rats.Journal of visualized experiments : JoVE · 2024Article
- Inactivity-induced phrenic motor facilitation requires PKCζ activity within phrenic motor neurons.Journal of neurophysiology · 2024Article
- Cervical spinal cord hemisection impacts sigh and the respiratory reset in male rats.Physiological reports · 2024Article
- Neurotrophic Natural Products.Progress in the chemistry of organic natural products · 2024Article
- Novel regenerative drug, SPG302 promotes functional recovery of diaphragm muscle activity after cervical spinal cord injury.The Journal of physiology · 2023Article
- Review
- Targeting drug or gene delivery to the phrenic motoneuron pool.Journal of neurophysiology · 2023Review
- Respiratory plasticity following spinal cord injury: perspectives from mouse to man.Neural regeneration research · 2022Review
- Cervical spinal hemisection alters phrenic motor neuron glutamatergic mRNA receptor expression.Experimental neurology · 2022Article
- The phrenic neuromuscular system.Handbook of clinical neurology · 2022Review
- Phrenic motor neuron survival below cervical spinal cord hemisection.Experimental neurology · 2021Article
- Electrical epidural stimulation of the cervical spinal cord: implications for spinal respiratory neuroplasticity after spinal cord injury.Journal of neurophysiology · 2021Review
- Acute intrathecal BDNF enhances functional recovery after cervical spinal cord injury in rats.Journal of neurophysiology · 2021Article
- Quantifying mitochondrial volume density in phrenic motor neurons.Journal of neuroscience methods · 2021Article
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
Progressive recovery of rhythmic phrenic activity occurs over time after a spinal cord hemisection involving unilateral transection of anterolateral funiculi at C2 (SH). Brain-derived neurotrophic factor (BDNF) acting through its full-length tropomyosin related kinase receptor subtype B (TrkB.FL) contributes to neuroplasticity after spinal cord injury, but the specific cellular substrates remain unclear. We hypothesized that selectively targeting increased TrkB.FL expression to phrenic motoneurons would be sufficient to enhance recovery of rhythmic phrenic activity after SH. Several adeno-associated virus (AAV) serotypes expressing GFP were screened to determine specificity for phrenic motoneuron transduction via intrapleural injection in adult rats. GFP expression was present in the cervical spinal cord 3 weeks after treatment with AAV serotypes 7, 8, and 9, but not with AAV2, 6, or rhesus-10. Overall, AAV7 produced the most consistent GFP expression in phrenic motoneurons. SH was performed 3 weeks after intrapleural injection of AAV7 expressing human TrkB.FL-FLAG or saline. Delivery of TrkB.FL-FLAG to phrenic motoneurons was confirmed by FLAG protein expression in the phrenic motor nucleus and human TrkB.FL mRNA expression in microdissected phrenic motoneurons. In all SH rats, absence of ipsilateral diaphragm EMG activity was confirmed at 3 days post-SH, verifying complete interruption of ipsilateral descending drive to phrenic motoneurons. At 14 days post-SH, all AAV7-TrkB.FL treated rats (n = 11) displayed recovery of ipsilateral diaphragm EMG activity compared to 3 out of 8 untreated SH rats (p<0.01). During eupnea, AAV7-TrkB.FL treated rats exhibited 73±7% of pre-SH root mean squared EMG vs. only 31±11% in untreated SH rats displaying recovery (p<0.01). This study provides direct evidence that increased TrkB.FL expression in phrenic motoneurons is sufficient to enhance recovery of ipsilateral rhythmic phrenic activity after SH, indicating that selectively targeting gene expression in spared motoneurons below the level of spinal cord injury may promote functional recovery.
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