Aged rats have an altered immune response and worse outcomes after traumatic brain injury

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Abstract

Initial studies suggest that increased age is associated with worse outcomes after traumatic brain injury (TBI), though the pathophysiological mechanisms responsible for this remain unclear. Immunosenescence (i.e., dysregulation of the immune system due to aging) may play a significant role in influencing TBI outcomes. This study therefore examined neurological outcomes and immune response in young-adult (i.e., 10 weeks old) compared to middle-aged (i.e., 1 year old) rats following a TBI (i.e., fluid percussion) or sham-injury. Rats were euthanized at either 24 h or one-week post-injury to analyze immune cell populations in the brain and periphery via flow cytometry, as well as telomere length (i.e., a biomarker of neurological health). Behavioral testing, as well as volumetric and diffusion-weighted MRI, were also performed in the one-week recovery rats to assess for functional deficits and brain damage. Middle-aged rats had worse sensorimotor deficits and shorter telomeres after TBI compared to young rats. Both aging and TBI independently worsened cognitive function and cortical volume. These changes occurred in the presence of fewer total leukocytes, fewer infiltrating myeloid cells, and fewer microglia in the brains of middle-aged TBI rats compared to young rats. These findings indicate that middle-aged rats have worse sensorimotor deficits and shorter telomeres after TBI than young rats, and this may be related to an altered neuroimmune response. Although further studies are required, these findings have important implications for understanding the pathophysiology and optimal treatment strategies in TBI patients across the life span.

Original languageEnglish
Pages (from-to)1-15
Number of pages15
JournalBrain, Behavior, and Immunity
DOIs
Publication statusAccepted/In press - 27 Apr 2019

Keywords

  • Aging
  • DTI
  • Immunology
  • Immunosenescence
  • MRI
  • Neuroinflammation

Cite this

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title = "Aged rats have an altered immune response and worse outcomes after traumatic brain injury",
abstract = "Initial studies suggest that increased age is associated with worse outcomes after traumatic brain injury (TBI), though the pathophysiological mechanisms responsible for this remain unclear. Immunosenescence (i.e., dysregulation of the immune system due to aging) may play a significant role in influencing TBI outcomes. This study therefore examined neurological outcomes and immune response in young-adult (i.e., 10 weeks old) compared to middle-aged (i.e., 1 year old) rats following a TBI (i.e., fluid percussion) or sham-injury. Rats were euthanized at either 24 h or one-week post-injury to analyze immune cell populations in the brain and periphery via flow cytometry, as well as telomere length (i.e., a biomarker of neurological health). Behavioral testing, as well as volumetric and diffusion-weighted MRI, were also performed in the one-week recovery rats to assess for functional deficits and brain damage. Middle-aged rats had worse sensorimotor deficits and shorter telomeres after TBI compared to young rats. Both aging and TBI independently worsened cognitive function and cortical volume. These changes occurred in the presence of fewer total leukocytes, fewer infiltrating myeloid cells, and fewer microglia in the brains of middle-aged TBI rats compared to young rats. These findings indicate that middle-aged rats have worse sensorimotor deficits and shorter telomeres after TBI than young rats, and this may be related to an altered neuroimmune response. Although further studies are required, these findings have important implications for understanding the pathophysiology and optimal treatment strategies in TBI patients across the life span.",
keywords = "Aging, DTI, Immunology, Immunosenescence, MRI, Neuroinflammation",
author = "Mujun Sun and Brady, {Rhys D.} and Casillas-Espinosa, {Pablo M.} and Wright, {David K.} and Semple, {Bridgette D.} and Kim, {Hyun Ah} and Richelle Mychasiuk and Sobey, {Christopher G.} and O'Brien, {Terence J.} and Antony Vinh and McDonald, {Stuart J.} and Shultz, {Sandy R.}",
year = "2019",
month = "4",
day = "27",
doi = "10.1016/j.bbi.2019.04.038",
language = "English",
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journal = "Brain, Behavior, and Immunity",
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T1 - Aged rats have an altered immune response and worse outcomes after traumatic brain injury

AU - Sun, Mujun

AU - Brady, Rhys D.

AU - Casillas-Espinosa, Pablo M.

AU - Wright, David K.

AU - Semple, Bridgette D.

AU - Kim, Hyun Ah

AU - Mychasiuk, Richelle

AU - Sobey, Christopher G.

AU - O'Brien, Terence J.

AU - Vinh, Antony

AU - McDonald, Stuart J.

AU - Shultz, Sandy R.

PY - 2019/4/27

Y1 - 2019/4/27

N2 - Initial studies suggest that increased age is associated with worse outcomes after traumatic brain injury (TBI), though the pathophysiological mechanisms responsible for this remain unclear. Immunosenescence (i.e., dysregulation of the immune system due to aging) may play a significant role in influencing TBI outcomes. This study therefore examined neurological outcomes and immune response in young-adult (i.e., 10 weeks old) compared to middle-aged (i.e., 1 year old) rats following a TBI (i.e., fluid percussion) or sham-injury. Rats were euthanized at either 24 h or one-week post-injury to analyze immune cell populations in the brain and periphery via flow cytometry, as well as telomere length (i.e., a biomarker of neurological health). Behavioral testing, as well as volumetric and diffusion-weighted MRI, were also performed in the one-week recovery rats to assess for functional deficits and brain damage. Middle-aged rats had worse sensorimotor deficits and shorter telomeres after TBI compared to young rats. Both aging and TBI independently worsened cognitive function and cortical volume. These changes occurred in the presence of fewer total leukocytes, fewer infiltrating myeloid cells, and fewer microglia in the brains of middle-aged TBI rats compared to young rats. These findings indicate that middle-aged rats have worse sensorimotor deficits and shorter telomeres after TBI than young rats, and this may be related to an altered neuroimmune response. Although further studies are required, these findings have important implications for understanding the pathophysiology and optimal treatment strategies in TBI patients across the life span.

AB - Initial studies suggest that increased age is associated with worse outcomes after traumatic brain injury (TBI), though the pathophysiological mechanisms responsible for this remain unclear. Immunosenescence (i.e., dysregulation of the immune system due to aging) may play a significant role in influencing TBI outcomes. This study therefore examined neurological outcomes and immune response in young-adult (i.e., 10 weeks old) compared to middle-aged (i.e., 1 year old) rats following a TBI (i.e., fluid percussion) or sham-injury. Rats were euthanized at either 24 h or one-week post-injury to analyze immune cell populations in the brain and periphery via flow cytometry, as well as telomere length (i.e., a biomarker of neurological health). Behavioral testing, as well as volumetric and diffusion-weighted MRI, were also performed in the one-week recovery rats to assess for functional deficits and brain damage. Middle-aged rats had worse sensorimotor deficits and shorter telomeres after TBI compared to young rats. Both aging and TBI independently worsened cognitive function and cortical volume. These changes occurred in the presence of fewer total leukocytes, fewer infiltrating myeloid cells, and fewer microglia in the brains of middle-aged TBI rats compared to young rats. These findings indicate that middle-aged rats have worse sensorimotor deficits and shorter telomeres after TBI than young rats, and this may be related to an altered neuroimmune response. Although further studies are required, these findings have important implications for understanding the pathophysiology and optimal treatment strategies in TBI patients across the life span.

KW - Aging

KW - DTI

KW - Immunology

KW - Immunosenescence

KW - MRI

KW - Neuroinflammation

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U2 - 10.1016/j.bbi.2019.04.038

DO - 10.1016/j.bbi.2019.04.038

M3 - Article

SP - 1

EP - 15

JO - Brain, Behavior, and Immunity

JF - Brain, Behavior, and Immunity

SN - 0889-1591

ER -