Chondroitinase improves anatomical and functional outcomes after primate spinal cord injury

Autor: Rod Moseanko, Leif A. Havton, Ernesto A. Salegio, Mark H. Tuszynski, James W. Fawcett, Adam R. Ferguson, Janet L. Weber, Jennifer Iaci, Stephanie Hawbecker, J. Russell Huie, Yvette S. Nout-Lomas, Barbara Haenzi, John H. Brock, Roger Pender, Jacqueline C. Bresnahan, Michael S. Beattie, Andrew R. Blight, Chase A. Weinholtz, Ephron S. Rosenzweig, Christina Cruzen, Justine J. Liang, Anthony O. Caggiano
Přispěvatelé: Fawcett, James [0000-0002-7990-4568], Apollo - University of Cambridge Repository
Rok vydání: 2019
Předmět:
0301 basic medicine
Male
Pathology
Swine
Pyramidal Tracts
Neurodegenerative
Injections
Intralesional
0302 clinical medicine
Psychology
Primate
Gray Matter
Spinal Cord Injury
Spinal cord injury
Motor Neurons
biology
General Neuroscience
Perineuronal net
3. Good health
Intralesional
medicine.anatomical_structure
Treatment Outcome
Neurological
Cognitive Sciences
Microglia
medicine.symptom
medicine.medical_specialty
Physical Injury - Accidents and Adverse Effects
Inhibitory postsynaptic potential
Article
Injections
Lesion
03 medical and health sciences
biology.animal
medicine
Extracellular
Animals
Traumatic Head and Spine Injury
Spinal Cord Injuries
Hand function
Neurology & Neurosurgery
business.industry
Neurosciences
Recovery of Function
Spinal cord
medicine.disease
Hand
Macaca mulatta
Axons
Chondroitinases and Chondroitin Lyases
030104 developmental biology
Synapses
business
Neuroscience
030217 neurology & neurosurgery
Psychomotor Performance
Zdroj: Nature neuroscience, vol 22, iss 8
Nature neuroscience
Popis: Inhibitory extracellular matrices form around mature neurons as perineuronal nets containing chondroitin sulfate proteoglycans that limit axonal sprouting after CNS injury. The enzyme chondroitinase (Chase) degrades inhibitory chondroitin sulfate proteoglycans and improves axonal sprouting and functional recovery after spinal cord injury in rodents. We evaluated the effects of Chase in rhesus monkeys that had undergone C7 spinal cord hemisection. Four weeks after hemisection, we administered multiple intraparenchymal Chase injections below the lesion, targeting spinal cord circuits that control hand function. Hand function improved significantly in Chase-treated monkeys relative to vehicle-injected controls. Moreover, Chase significantly increased corticospinal axon growth and the number of synapses formed by corticospinal terminals in gray matter caudal to the lesion. No detrimental effects were detected. This approach appears to merit clinical translation in spinal cord injury.
Databáze: OpenAIRE
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