Journal article
A hydrogel engineered to deliver minocycline locally to the injured cervical spinal cord protects respiratory neural circuitry and preserves diaphragm function
Neurobiology of disease, v 127, pp 591-604
01 Jul 2019
PMID: 31028873
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
We tested a biomaterial-based approach to preserve the critical phrenic motor circuitry that controls diaphragm function by locally delivering minocycline hydrochloride (MH) following cervical spinal cord injury (SCI). MH is a clinically-available antibiotic and anti-inflammatory drug that targets a broad range of secondary injury mechanisms via its anti-inflammatory, anti-oxidant and anti-apoptotic properties. However, MH is only neuroprotective at high concentrations that cannot be achieved by systemic administration, which limits its clinical efficacy. We have developed a hydrogel-based MH delivery system that can be injected into the intrathecal space for local delivery of high concentrations of MH, without damaging spinal cord tissue. Implantation of MH hydrogel after unilateral level-C4/5 contusion SCI robustly preserved diaphragm function, as assessed by in vivo recordings of compound muscle action potential (CMAP) and electromyography (EMG) amplitudes. MH hydrogel also decreased lesion size and degeneration of cervical motor neuron somata, demonstrating its central neuroprotective effects within the injured cervical spinal cord. Furthermore, MH hydrogel significantly preserved diaphragm innervation by the axons of phrenic motor neurons (PhMNs), as assessed by both detailed neuromuscular junction (NMJ) morphological analysis and retrograde PhMN labeling from the diaphragm using cholera toxin B (CTB). In conclusion, our findings demonstrate that local MH hydrogel delivery to the injured cervical spinal cord is effective in preserving respiratory function after SCI by protecting the important neural circuitry that controls diaphragm activation.
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Details
- Title
- A hydrogel engineered to deliver minocycline locally to the injured cervical spinal cord protects respiratory neural circuitry and preserves diaphragm function
- Creators
- Biswarup Ghosh - Thomas Jefferson UniversityJia Nong - Drexel UniversityZhicheng Wang - Drexel UniversityMark W. Urban - Thomas Jefferson UniversityNicolette M. Heinsinger - Thomas Jefferson UniversityVictoria A. Trovillion - Thomas Jefferson UniversityMegan C. Wright - Arcadia UniversityAngelo C. Lepore - Thomas Jefferson UniversityYinghui Zhong - Drexel University
- Publication Details
- Neurobiology of disease, v 127, pp 591-604
- Publisher
- Elsevier
- Number of pages
- 14
- Grant note
- R01NS079702 / 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) Pennsylvania Tobacco -Commonwealth Universal Research Enhancement (CURE) Research Program 476686 / Craig H. Neilsen Foundation 2R01NS079702-06 / National Institutes of Health; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA Margaret Q. Landenberger Research Foundation
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Pharmacology and Physiology; School of Biomedical Engineering, Science, and Health Systems
- Web of Science ID
- WOS:000472990100051
- Scopus ID
- 2-s2.0-85064748888
- Other Identifier
- 991019167596904721
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- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Neurosciences