Axon Degeneration Is Rescued with Human Umbilical Cord Perivascular Cells: A Potential Candidate for Neuroprotection After Traumatic Brain Injury
| Autor: | Tanya Barretto, Katya Park, Denis Gallagher, Shlomit Kenigsberg, Elaine Liu, Eugene Park, Leila Maghen, Andrew J Baker, Clifford Librach, Andrée Gauthier-Fisher |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Traumatic brain injury Morpholines Primary Cell Culture Cell- and Tissue-Based Therapy Potential candidate Superior Cervical Ganglion Biology Umbilical cord Neuroprotection Umbilical Cord Rats Sprague-Dawley 03 medical and health sciences 0302 clinical medicine Neurofilament Proteins Brain Injuries Traumatic Nerve Growth Factor medicine Animals Humans Neurons Cell Biology Hematology Cortical neurons Fibroblasts Embryo Mammalian medicine.disease Axons Coculture Techniques Rats Oxygen Disease Models Animal Glucose 030104 developmental biology medicine.anatomical_structure Gene Expression Regulation Chromones Pericytes Proto-Oncogene Proteins c-akt Neuroscience 030217 neurology & neurosurgery Developmental Biology Axon degeneration |
| Zdroj: | Stem Cells and Development. 29:198-211 |
| ISSN: | 1557-8534 1547-3287 |
| Popis: | Traumatic brain injury (TBI) leads to delayed secondary injury events consisting of cellular and molecular cascades that exacerbate the initial injury. Human umbilical cord perivascular cells (HUCPVCs) secrete neurotrophic and prosurvival factors. In this study, we examined the effects of HUCPVC in sympathetic axon and cortical axon survival models and sought to determine whether HUCPVC provide axonal survival cues. We then examined the effects of the HUCPVC in an in vivo fluid percussion injury model of TBI. Our data indicate that HUCPVCs express neurotrophic and neural survival factors. They also express and secrete relevant growth and survival proteins when cultured alone, or in the presence of injured axons. Coculture experiments indicate that HUCPVCs interact preferentially with axons when cocultured with sympathetic neurons and reduce axonal degeneration. Nerve growth factor withdrawal in axonal compartments resulted in 66 ± 3% axon degeneration, whereas HUCPVC coculture rescued axon degeneration to 35 ± 3%. Inhibition of Akt (LY294002) resulted in a significant increase in degeneration compared with HUCPVC cocultures (48 ± 7% degeneration). Under normoxic conditions, control cultures showed 39 ± 5% degeneration. Oxygen glucose deprivation (OGD) resulted in 58 ± 3% degeneration and OGD HUCPVC cocultures reduced degeneration to 34 ± 5% ( |
| Databáze: | OpenAIRE |
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