Surgical Lumbar Sympathectomy in Mice

Peripheral nerve injuries are common, and full functional recovery after injury is achieved in only 10% of patients. The sympathetic nervous system plays ...

Emory University School of Medicine

Emory University

Enhancing axon regeneration is a major focus of nerve injury research, and the quality of the surgical nerve repair plays a large role in the aggregate success of nerve regeneration. Additionally, exercise is known to promote successful axon regeneration after surgical nerve repair. In this study, we asked how exercise-induced nerve regeneration is affected when a transected nerve is repaired with or without fibrin glue. Fibrin glue repaired nerves exhibited greater vasculature within the tissue bridge compared to nerves that were intrinsically repaired. Fibrin glue repaired nerves also exhibited more robust axon regeneration after exercise compared to nerves that were not repaired with fibrin glue. When angiogenesis of the tissue bridge was prevented, exercise was unable to enhance regeneration despite the presence of fibrin glue. These findings suggest that the biological properties of fibrin glue enhance angiogenesis within the repair site, and a vascularized bridge is required for enhanced axon elongation with exercise. The combination of fibrin glue repair and exercise resulted in notable differences in vascular growth, axon elongation, neuromuscular junction reinnervation, and functional recovery. Fibrin glue should be considered as an adjuvant for nerve repair to enhance the subsequent efficacy of activity- and physical therapy-based treatment interventions.

Angiogenesis is critical for the exercise-mediated enhancement of axon regeneration following peripheral nerve injury.

Primary sensory dorsal root ganglia (DRG) neurons are diverse, with distinct populations that respond to specific stimuli. Previously, we observed that functionally distinct populations of DRG neurons express mRNA transcript variants with different 3' untranslated regions (3'UTRs). 3'UTRs harbor binding sites for interaction with RNA-binding proteins (RBPs) for transporting mRNAs to subcellular domains, modulating transcript stability, and regulating the rate of translation. In the current study, analysis of publicly available single-cell RNA-sequencing data generated from adult mice revealed that 17 3'UTR-binding RBPs were enriched in specific populations of DRG neurons. This included four members of the CUG triplet repeat (CUGBP) Elav-like family (CELF): CELF2 and CELF4 were enriched in peptidergic, CELF6 in both peptidergic and nonpeptidergic, and CELF3 in tyrosine hydroxylase-expressing neurons. Immunofluorescence studies confirmed that 60% of CELF4+ neurons are small-diameter C fibers and 33% medium-diameter myelinated (likely Aδ) fibers and showed that CELF4 is distributed to peripheral termini. Coexpression analyses using transcriptomic data and immunofluorescence revealed that CELF4 is enriched in nociceptive neurons that express GFRA3, CGRP, and the capsaicin receptor TRPV1. Reanalysis of published transcriptomic data from macaque DRG revealed a highly similar distribution of CELF members, and reanalysis of single-nucleus RNA-sequencing data derived from mouse and rat DRG after sciatic injury revealed differential expression of CELFs in specific populations of sensory neurons. We propose that CELF RBPs may regulate the fate of mRNAs in populations of nociceptors, and may play a role in pain and/or neuronal regeneration following nerve injury.

Members of the CUGBP Elav-like family of RNA-binding proteins are expressed in distinct populations of primary sensory neurons.

 An 8-week educational intervention co-taught by medical students and faculty was designed to foster communication between clinical researchers and populations of interest to ultimately increase participation in clinical research by older adults, including underrepresented groups. Weekly topics focused on age-related changes and health conditions, socio-contextual factors impacting aging populations, and wellness strategies.  To evaluate the successes and weaknesses of an educational intervention aimed at increasing the participation of older adults in clinical research.  A focus group was assembled after an 8-week educational intervention, titled DREAMS, to obtain participants' feedback on the program, following a pre-formulated interview guide.  Participants were interviewed in a health center office environment in the United States of America in April of 2016.  A post-intervention focus group was conducted with a group of eight older adults (mean age = 75.8 ± 11.4 years) from 51 total participants who completed the intervention.  The focus group was interviewed loosely following a pre-formed question guide. Participants were encouraged to give honest feedback. The conversation was recorded, transcribed verbatim, and analyzed using thematic analyses.  While participants viewed most aspects of the study as a success and stated that it was a productive learning experience, most participants had suggestions for improvements in the program content and implementation. Specifically, the composition of and direction to small breakout groups should be carefully considered and planned in this population, and attention should be paid to the delivery of sensitive topic such as death and dementia. A clear main benefit of this programmatic approach is the development of a rapport amongst participants and between participants and clinical researchers.  The results provide useful insights regarding improving participation among hard-to-reach and historically underrepresented groups of older adults in clinical research. Future iterations of this program and similar educational interventions can use these findings to better achieve the programmatic objectives.

Interpretive Qualitative Evaluation Informs Research Participation and Advocacy Training Program for Seniors: A Pilot Study.

Peripheral nerve injuries (PNIs) are common and devastating. The current standard of care relies on the slow and inefficient process of nerve regeneration after surgical intervention. Electrical stimulation (ES) has been shown to both experimentally and clinically result in improved regeneration and functional recovery after PNI for motor and sensory neurons; however, its effects on sympathetic regeneration have never been studied. Sympathetic neurons are responsible for a myriad of homeostatic processes that include, but are not limited to, blood pressure, immune response, sweating, and the structural integrity of the neuromuscular junction. Almost one quarter of the axons in the sciatic nerve are from sympathetic neurons, and their importance in bodily homeostasis and the pathogenesis of neuropathic pain should not be underestimated. Therefore, as ES continues to make its way into patient care, it is not only important to understand its impact on all neuron subtypes, but also to ensure that potential adverse effects are minimized. This piece gives an overview of the effects of ES in animals models and in humans while offering a perspective on the potential effects of ES on sympathetic axon regeneration.

Article	Year
Angiogenesis is critical for the exercise-mediated enhancement of axon regeneration following peripheral nerve injury. Experimental neurology\| PubMed ID: 35259353	2022
Members of the CUGBP Elav-like family of RNA-binding proteins are expressed in distinct populations of primary sensory neurons. The Journal of comparative neurology\| PubMed ID: 37537886	2023
Interpretive Qualitative Evaluation Informs Research Participation and Advocacy Training Program for Seniors: A Pilot Study. Healthcare (Basel, Switzerland)\| PubMed ID: 37830715	2023
A Perspective on Electrical Stimulation and Sympathetic Regeneration in Peripheral Nerve Injuries. Neurotrauma reports\| PubMed ID: 38463421	2024

Tina Tian

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