Journal article
Perineuronal Net Changes Reveal a Distinct Right and Left Spinal Phrenic Circuit
Journal of neurotrauma, v 42(23-24), pp 2204-2216
10 Dec 2025
PMID: 40435933
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Respiratory failure is one of the greatest causes of morbidity and mortality after cervical lesions, the most common type of spinal cord injury (SCI). Fortunately, several pre-clinical and clinical studies have shown spontaneous, but limited, respiratory recovery after injury. However, there are still many unanswered questions about what is driving this recovery, so there is a growing need to further elucidate the neuroplastic potential of the phrenic network. Here, we investigated the structural plasticity of the right and left phrenic networks by analyzing perineuronal net (PNN) changes after a C2 hemisection (C2Hx) in mice. For this purpose, the right and left phrenic systems were traced with a pseudorabies virus, a trans-synaptic retrograde tracer applied to the diaphragm muscle, labeling the entire phrenic motor network. We found most PNN-bearing neurons within the ventral horn in naïve animals, specifically around phrenic motoneurons (PhMNs), but not phrenic spinal interneurons. Right, but not left, C2Hx resulted in a significant increase in PNNs and glutamatergic synapses around ipsilateral PhMNs, suggesting that the right C2Hx requires greater neuroplasticity to overcome respiratory dysfunction. The results from this study uncover profound anatomical and functional asymmetries in left- and right-sided phrenic networks, underlying the complex nature of the spinal respiratory system, and contribute to a more advanced understanding of how the phrenic network adapts to trauma. Overall, this work underscores the importance of studying neuroplasticity and how it holds the potential to help improve outcomes for individuals living with SCI.
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Details
- Title
- Perineuronal Net Changes Reveal a Distinct Right and Left Spinal Phrenic Circuit
- Creators
- Judith Sánchez-Ventura - Centro de Investigación Biomédica en RedKayla Anne Schardien - The Marion Murray Spinal Cord Research Center, College of Medicine, Drexel University, Philadelphia, Pennsylvania, USATara Fortino - Drexel University, Neurobiology and AnatomyLana V Zholudeva - Drexel University, Neurobiology and AnatomyMichael A Lane - Drexel University, Neurobiology and AnatomyEsther Udina - Centro de Investigación Biomédica en Red
- Publication Details
- Journal of neurotrauma, v 42(23-24), pp 2204-2216
- Publisher
- Mary Ann Liebert
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Biochemistry and Molecular Biology; Neurobiology and Anatomy
- Web of Science ID
- WOS:001497600700001
- Scopus ID
- 2-s2.0-105006981362
- Other Identifier
- 991022054406304721
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- Collaboration types
- Domestic collaboration
- International collaboration
- Web of Science research areas
- Clinical Neurology
- Critical Care Medicine
- Neurosciences