Cargando…
Age-related changes in plasma extracellular vesicles influence neuroinflammation in the brain and neurological outcome after traumatic spinal cord injury
Approximately 20% of all spinal cord injuries (SCI) occur in persons aged 65 years or older. Longitudinal, population-based studies showed that SCI is a risk factor for dementia. However, little research has addressed the potential mechanisms of SCI-mediated neurological impairment in the elderly. W...
Autores principales: | , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Journal Experts
2023
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10153385/ https://www.ncbi.nlm.nih.gov/pubmed/37131758 http://dx.doi.org/10.21203/rs.3.rs-2821858/v1 |
_version_ | 1785035919889268736 |
---|---|
author | Lei, Zhuofan Krishnamachary, Balaji Ritzel, Rodney M. Khan, Niaz Z. Li, Yun Li, Hui Brunner, Kavitha Faden, Alan I. Wu, Junfang |
author_facet | Lei, Zhuofan Krishnamachary, Balaji Ritzel, Rodney M. Khan, Niaz Z. Li, Yun Li, Hui Brunner, Kavitha Faden, Alan I. Wu, Junfang |
author_sort | Lei, Zhuofan |
collection | PubMed |
description | Approximately 20% of all spinal cord injuries (SCI) occur in persons aged 65 years or older. Longitudinal, population-based studies showed that SCI is a risk factor for dementia. However, little research has addressed the potential mechanisms of SCI-mediated neurological impairment in the elderly. We compared young adult and aged C57BL/6 male mice subjected to contusion SCI, using a battery of neurobehavioral tests. Locomotor function showed greater impairment in aged mice, which was correlated with reduced, spared spinal cord white matter and increased lesion volume. At 2 months post-injury, aged mice displayed worse performance in cognitive and depressive-like behavioral tests. Transcriptomic analysis identified activated microglia and dysregulated autophagy as the most significantly altered pathways by both age and injury. Flow cytometry demonstrated increased myeloid and lymphocyte infiltration at both the injury site and brain of aged mice. SCI in aged mice was associated with altered microglial function and dysregulated autophagy involving both microglia and brain neurons. Altered plasma extracellular vesicles (EVs) responses were found in aged mice after acute SCI. EV-microRNA cargos were also significantly altered by aging and injury, which were associated with neuroinflammation and autophagy dysfunction. In cultured microglia, astrocytes, and neurons, plasma EVs from aged SCI mice, at a lower concentration comparable to those of young adult SCI mice, induced the secretion of pro-inflammatory cytokines CXCL2 and IL-6, and increased caspase3 expression. Together, these findings suggest that age alters the EVs pro-inflammatory response to SCI, potentially contributing to worse neuropathological and functional outcomes. |
format | Online Article Text |
id | pubmed-10153385 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | American Journal Experts |
record_format | MEDLINE/PubMed |
spelling | pubmed-101533852023-05-03 Age-related changes in plasma extracellular vesicles influence neuroinflammation in the brain and neurological outcome after traumatic spinal cord injury Lei, Zhuofan Krishnamachary, Balaji Ritzel, Rodney M. Khan, Niaz Z. Li, Yun Li, Hui Brunner, Kavitha Faden, Alan I. Wu, Junfang Res Sq Article Approximately 20% of all spinal cord injuries (SCI) occur in persons aged 65 years or older. Longitudinal, population-based studies showed that SCI is a risk factor for dementia. However, little research has addressed the potential mechanisms of SCI-mediated neurological impairment in the elderly. We compared young adult and aged C57BL/6 male mice subjected to contusion SCI, using a battery of neurobehavioral tests. Locomotor function showed greater impairment in aged mice, which was correlated with reduced, spared spinal cord white matter and increased lesion volume. At 2 months post-injury, aged mice displayed worse performance in cognitive and depressive-like behavioral tests. Transcriptomic analysis identified activated microglia and dysregulated autophagy as the most significantly altered pathways by both age and injury. Flow cytometry demonstrated increased myeloid and lymphocyte infiltration at both the injury site and brain of aged mice. SCI in aged mice was associated with altered microglial function and dysregulated autophagy involving both microglia and brain neurons. Altered plasma extracellular vesicles (EVs) responses were found in aged mice after acute SCI. EV-microRNA cargos were also significantly altered by aging and injury, which were associated with neuroinflammation and autophagy dysfunction. In cultured microglia, astrocytes, and neurons, plasma EVs from aged SCI mice, at a lower concentration comparable to those of young adult SCI mice, induced the secretion of pro-inflammatory cytokines CXCL2 and IL-6, and increased caspase3 expression. Together, these findings suggest that age alters the EVs pro-inflammatory response to SCI, potentially contributing to worse neuropathological and functional outcomes. American Journal Experts 2023-04-17 /pmc/articles/PMC10153385/ /pubmed/37131758 http://dx.doi.org/10.21203/rs.3.rs-2821858/v1 Text en https://creativecommons.org/licenses/by/4.0/This work is licensed under a Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/) , which allows reusers to distribute, remix, adapt, and build upon the material in any medium or format, so long as attribution is given to the creator. The license allows for commercial use. https://creativecommons.org/licenses/by/4.0/License: This work is licensed under a Creative Commons Attribution 4.0 International License. Read Full License (https://creativecommons.org/licenses/by/4.0/) |
spellingShingle | Article Lei, Zhuofan Krishnamachary, Balaji Ritzel, Rodney M. Khan, Niaz Z. Li, Yun Li, Hui Brunner, Kavitha Faden, Alan I. Wu, Junfang Age-related changes in plasma extracellular vesicles influence neuroinflammation in the brain and neurological outcome after traumatic spinal cord injury |
title | Age-related changes in plasma extracellular vesicles influence neuroinflammation in the brain and neurological outcome after traumatic spinal cord injury |
title_full | Age-related changes in plasma extracellular vesicles influence neuroinflammation in the brain and neurological outcome after traumatic spinal cord injury |
title_fullStr | Age-related changes in plasma extracellular vesicles influence neuroinflammation in the brain and neurological outcome after traumatic spinal cord injury |
title_full_unstemmed | Age-related changes in plasma extracellular vesicles influence neuroinflammation in the brain and neurological outcome after traumatic spinal cord injury |
title_short | Age-related changes in plasma extracellular vesicles influence neuroinflammation in the brain and neurological outcome after traumatic spinal cord injury |
title_sort | age-related changes in plasma extracellular vesicles influence neuroinflammation in the brain and neurological outcome after traumatic spinal cord injury |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10153385/ https://www.ncbi.nlm.nih.gov/pubmed/37131758 http://dx.doi.org/10.21203/rs.3.rs-2821858/v1 |
work_keys_str_mv | AT leizhuofan agerelatedchangesinplasmaextracellularvesiclesinfluenceneuroinflammationinthebrainandneurologicaloutcomeaftertraumaticspinalcordinjury AT krishnamacharybalaji agerelatedchangesinplasmaextracellularvesiclesinfluenceneuroinflammationinthebrainandneurologicaloutcomeaftertraumaticspinalcordinjury AT ritzelrodneym agerelatedchangesinplasmaextracellularvesiclesinfluenceneuroinflammationinthebrainandneurologicaloutcomeaftertraumaticspinalcordinjury AT khanniazz agerelatedchangesinplasmaextracellularvesiclesinfluenceneuroinflammationinthebrainandneurologicaloutcomeaftertraumaticspinalcordinjury AT liyun agerelatedchangesinplasmaextracellularvesiclesinfluenceneuroinflammationinthebrainandneurologicaloutcomeaftertraumaticspinalcordinjury AT lihui agerelatedchangesinplasmaextracellularvesiclesinfluenceneuroinflammationinthebrainandneurologicaloutcomeaftertraumaticspinalcordinjury AT brunnerkavitha agerelatedchangesinplasmaextracellularvesiclesinfluenceneuroinflammationinthebrainandneurologicaloutcomeaftertraumaticspinalcordinjury AT fadenalani agerelatedchangesinplasmaextracellularvesiclesinfluenceneuroinflammationinthebrainandneurologicaloutcomeaftertraumaticspinalcordinjury AT wujunfang agerelatedchangesinplasmaextracellularvesiclesinfluenceneuroinflammationinthebrainandneurologicaloutcomeaftertraumaticspinalcordinjury |