Age-At-Injury Influences the Glial Response to Traumatic Brain Injury in the Cortex of Male Juvenile Rats
Few translational studies have examined how age-at-injury affects the glial response to traumatic brain injury (TBI). We hypothesized that rats injured at post-natal day (PND) 17 would exhibit a greater glial response, that would persist into early adulthood, compared to rats injured at PND35. PND17...
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Frontiers Media S.A.
2022-01-01
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| Series: | Frontiers in Neurology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fneur.2021.804139/full |
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| author | Tabitha R. F. Green Sean M. Murphy J. Bryce Ortiz J. Bryce Ortiz Rachel K. Rowe Rachel K. Rowe Rachel K. Rowe |
| author_facet | Tabitha R. F. Green Sean M. Murphy J. Bryce Ortiz J. Bryce Ortiz Rachel K. Rowe Rachel K. Rowe Rachel K. Rowe |
| author_sort | Tabitha R. F. Green |
| collection | DOAJ |
| description | Few translational studies have examined how age-at-injury affects the glial response to traumatic brain injury (TBI). We hypothesized that rats injured at post-natal day (PND) 17 would exhibit a greater glial response, that would persist into early adulthood, compared to rats injured at PND35. PND17 and PND35 rats (n = 75) received a mild to moderate midline fluid percussion injury or sham surgery. In three cortical regions [peri-injury, primary somatosensory barrel field (S1BF), perirhinal], we investigated the glial response relative to age-at-injury (PND17 or PND35), time post-injury (2 hours, 1 day, 7 days, 25 days, or 43 days), and post-natal age, such that rats injured at PND17 or PND35 were compared at the same post-natal-age (e.g., PND17 + 25D post-injury = PND42; PND35 + 7D post-injury = PND42). We measured Iba1 positive microglia cells (area, perimeter) and quantified their activation status using skeletal analysis (branch length/cell, mean processes/cell, cell abundance). GFAP expression was examined using immunohistochemistry and pixel analysis. Data were analyzed using Bayesian multivariate multi-level models. Independent of age-at-injury, TBI activated microglia (shorter branches, fewer processes) in the S1BF and perirhinal cortex with more microglia in all regions compared to uninjured shams. TBI-induced microglial activation (shorter branches) was sustained in the S1BF into early adulthood (PND60). Overall, PND17 injured rats had more microglial activation in the perirhinal cortex than PND35 injured rats. Activation was not confounded by age-dependent cell size changes, and microglial cell body sizes were similar between PND17 and PND35 rats. There were no differences in astrocyte GFAP expression. Increased microglial activation in PND17 brain-injured rats suggests that TBI upregulates the glial response at discrete stages of development. Age-at-injury and aging with an injury are translationally important because experiencing a TBI at an early age may trigger an exaggerated glial response. |
| first_indexed | 2024-04-11T18:21:28Z |
| format | Article |
| id | doaj.art-dffbc0cb5fb948589181a26ff1daf90b |
| institution | Directory Open Access Journal |
| issn | 1664-2295 |
| language | English |
| last_indexed | 2024-04-11T18:21:28Z |
| publishDate | 2022-01-01 |
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| series | Frontiers in Neurology |
| spelling | doaj.art-dffbc0cb5fb948589181a26ff1daf90b2022-12-22T04:09:45ZengFrontiers Media S.A.Frontiers in Neurology1664-22952022-01-011210.3389/fneur.2021.804139804139Age-At-Injury Influences the Glial Response to Traumatic Brain Injury in the Cortex of Male Juvenile RatsTabitha R. F. Green0Sean M. Murphy1J. Bryce Ortiz2J. Bryce Ortiz3Rachel K. Rowe4Rachel K. Rowe5Rachel K. Rowe6Department of Child Health, University of Arizona College of Medicine-Phoenix, Phoenix, AZ, United StatesDepartment of Child Health, University of Arizona College of Medicine-Phoenix, Phoenix, AZ, United StatesDepartment of Child Health, University of Arizona College of Medicine-Phoenix, Phoenix, AZ, United StatesPhoenix Veterans Affairs (VA) Health Care System, Phoenix, AZ, United StatesDepartment of Child Health, University of Arizona College of Medicine-Phoenix, Phoenix, AZ, United StatesDepartment of Integrative Physiology, University of Colorado, Boulder, CO, United StatesBARROW Neurological Institute at Phoenix Children's Hospital, Phoenix, AZ, United StatesFew translational studies have examined how age-at-injury affects the glial response to traumatic brain injury (TBI). We hypothesized that rats injured at post-natal day (PND) 17 would exhibit a greater glial response, that would persist into early adulthood, compared to rats injured at PND35. PND17 and PND35 rats (n = 75) received a mild to moderate midline fluid percussion injury or sham surgery. In three cortical regions [peri-injury, primary somatosensory barrel field (S1BF), perirhinal], we investigated the glial response relative to age-at-injury (PND17 or PND35), time post-injury (2 hours, 1 day, 7 days, 25 days, or 43 days), and post-natal age, such that rats injured at PND17 or PND35 were compared at the same post-natal-age (e.g., PND17 + 25D post-injury = PND42; PND35 + 7D post-injury = PND42). We measured Iba1 positive microglia cells (area, perimeter) and quantified their activation status using skeletal analysis (branch length/cell, mean processes/cell, cell abundance). GFAP expression was examined using immunohistochemistry and pixel analysis. Data were analyzed using Bayesian multivariate multi-level models. Independent of age-at-injury, TBI activated microglia (shorter branches, fewer processes) in the S1BF and perirhinal cortex with more microglia in all regions compared to uninjured shams. TBI-induced microglial activation (shorter branches) was sustained in the S1BF into early adulthood (PND60). Overall, PND17 injured rats had more microglial activation in the perirhinal cortex than PND35 injured rats. Activation was not confounded by age-dependent cell size changes, and microglial cell body sizes were similar between PND17 and PND35 rats. There were no differences in astrocyte GFAP expression. Increased microglial activation in PND17 brain-injured rats suggests that TBI upregulates the glial response at discrete stages of development. Age-at-injury and aging with an injury are translationally important because experiencing a TBI at an early age may trigger an exaggerated glial response.https://www.frontiersin.org/articles/10.3389/fneur.2021.804139/fullconcussionpediatricjuvenileinflammationmicrogliaastrocyte |
| spellingShingle | Tabitha R. F. Green Sean M. Murphy J. Bryce Ortiz J. Bryce Ortiz Rachel K. Rowe Rachel K. Rowe Rachel K. Rowe Age-At-Injury Influences the Glial Response to Traumatic Brain Injury in the Cortex of Male Juvenile Rats Frontiers in Neurology concussion pediatric juvenile inflammation microglia astrocyte |
| title | Age-At-Injury Influences the Glial Response to Traumatic Brain Injury in the Cortex of Male Juvenile Rats |
| title_full | Age-At-Injury Influences the Glial Response to Traumatic Brain Injury in the Cortex of Male Juvenile Rats |
| title_fullStr | Age-At-Injury Influences the Glial Response to Traumatic Brain Injury in the Cortex of Male Juvenile Rats |
| title_full_unstemmed | Age-At-Injury Influences the Glial Response to Traumatic Brain Injury in the Cortex of Male Juvenile Rats |
| title_short | Age-At-Injury Influences the Glial Response to Traumatic Brain Injury in the Cortex of Male Juvenile Rats |
| title_sort | age at injury influences the glial response to traumatic brain injury in the cortex of male juvenile rats |
| topic | concussion pediatric juvenile inflammation microglia astrocyte |
| url | https://www.frontiersin.org/articles/10.3389/fneur.2021.804139/full |
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