Files and links (1)
Published, Version of Record (VoR)Open Access (License Unspecified), Open
Journal article
Integration of Transplanted Neural Precursors with the Injured Cervical Spinal Cord
Journal of neurotrauma, v 35(15), pp 1781-1799
01 Aug 2018
PMID: 29295654
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Cervical spinal cord injuries (SCI) result in devastating functional consequences, including respiratory dysfunction. This is largely attributed to the disruption of phrenic pathways, which control the diaphragm. Recent work has identified spinal interneurons as possible contributors to respiratory neuroplasticity. The present work investigated whether transplantation of developing spinal cord tissue, inherently rich in interneuronal progenitors, could provide a population of new neurons and growth-permissive substrate to facilitate plasticity and formation of novel relay circuits to restore input to the partially denervated phrenic motor circuit. One week after a lateralized, C3/4 contusion injury, adult Sprague-Dawley rats received allografts of dissociated, developing spinal cord tissue (from rats at gestational days 13-14). Neuroanatomical tracing and terminal electrophysiology was performed on the graft recipients 1 month later. Experiments using pseudorabies virus (a retrograde, transynaptic tracer) revealed connections from donor neurons onto host phrenic circuitry and from host, cervical interneurons onto donor neurons. Anatomical characterization of donor neurons revealed phenotypic heterogeneity, though donor-host connectivity appeared selective. Despite the consistent presence of cholinergic interneurons within donor tissue, transneuronal tracing revealed minimal connectivity with host phrenic circuitry. Phrenic nerve recordings revealed changes in burst amplitude after application of a glutamatergic, but not serotonergic antagonist to the transplant, suggesting a degree of functional connectivity between donor neurons and host phrenic circuitry that is regulated by glutamatergic input. Importantly, however, anatomical and functional results were variable across animals, and future studies will explore ways to refine donor cell populations and entrain consistent connectivity.
Metrics
Details
- Title
- Integration of Transplanted Neural Precursors with the Injured Cervical Spinal Cord
- Creators
- Victoria M. Spruance - Drexel UniversityLyandysha V. Zholudeva - Drexel UniversityKristiina M. Hormigo - Drexel UniversityMargo L. Randelman - Drexel UniversityTatiana Bezdudnaya - Drexel UniversityVitaliy Marchenko - Drexel UniversityMichael A. Lane - Drexel University
- Publication Details
- Journal of neurotrauma, v 35(15), pp 1781-1799
- Publisher
- Mary Ann Liebert, Inc
- Number of pages
- 19
- Grant note
- SC140038 / United States Department of Defense 338432 / Craig H. Neilsen (Lane) Drexel Deans Fellowship for Collaborative or Themed Research P40 RR018604 / Virus Center funding R01NS081112 / NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Neurological Disorders & Stroke (NINDS) P01 NS 055976 / Spinal Cord Research Center at Drexel University, College of Medicine (NIH); United States Department of Health & Human Services; National Institutes of Health (NIH) - USA R01NS081112 / National Institute of Neurological Disorders and Stroke of the National Institutes of Health; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Neurological Disorders & Stroke (NINDS)
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Neurobiology and Anatomy; Neurology
- Web of Science ID
- WOS:000430751100001
- Scopus ID
- 2-s2.0-85049685225
- Other Identifier
- 991019167416704721
UN Sustainable Development Goals (SDGs)
This publication has contributed to the advancement of the following goals:
InCites Highlights
Data related to this publication, from InCites Benchmarking & Analytics tool:
- Web of Science research areas
- Clinical Neurology
- Critical Care Medicine
- Neurosciences