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Perineuronal Net Changes Reveal a Distinct Right and Left Spinal Phrenic Circuit
Journal article   Peer reviewed

Perineuronal Net Changes Reveal a Distinct Right and Left Spinal Phrenic Circuit

Judith Sánchez-Ventura, Kayla Anne Schardien, Tara Fortino, Lana V Zholudeva, Michael A Lane and Esther Udina
Journal of neurotrauma, v 42(23-24), pp 2204-2216
10 Dec 2025
PMID: 40435933
url
https://pmc.ncbi.nlm.nih.gov/articles/PMC13048106/View
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Abstract

Animals Diaphragm - innervation Female Male Mice Mice, Inbred C57BL Motor Neurons - pathology Motor Neurons - physiology Nerve Net - pathology Nerve Net - physiopathology Neuronal Plasticity - physiology Phrenic Nerve - pathology Phrenic Nerve - physiology Phrenic Nerve - physiopathology Spinal Cord Injuries - pathology Spinal Cord Injuries - physiopathology
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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Collaboration types
Domestic collaboration
International collaboration
Web of Science research areas
Clinical Neurology
Critical Care Medicine
Neurosciences
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