Acute peripheral immune activation alters cytokine expression and glial activation in the early postnatal rat brain

Matthew Bruce, Karin M. Streifel, Casey A. Boosalis, Luke Heuer, Eduardo A. González, Shuyang Li, Danielle J. Harvey, Pamela J. Lein, Judy Van De Water

Research output: Contribution to journalArticle

Abstract

Background: Neuroinflammation can modulate brain development; however, the influence of an acute peripheral immune challenge on neuroinflammatory responses in the early postnatal brain is not well characterized. To address this gap in knowledge, we evaluated the peripheral and central nervous system (CNS) immune responses to a mixed immune challenge in early postnatal rats of varying strains and sex. Methods: On postnatal day 10 (P10), male and female Lewis and Brown Norway rats were injected intramuscularly with either a mix of bacterial and viral components in adjuvant, adjuvant-only, or saline. Immune responses were evaluated at 2 and 5 days post-challenge. Cytokine and chemokine levels were evaluated in serum and in multiple brain regions using a Luminex multiplex assay. Multi-factor ANOVAs were used to compare analyte levels across treatment groups within strain, sex, and day of sample collection. Numbers and activation status of astrocytes and microglia were also analyzed in the cortex and hippocampus by quantifying immunoreactivity for GFAP, IBA-1, and CD68 in fixed brain slices. Immunohistochemical data were analyzed using a mixed-model regression analysis. Results: Acute peripheral immune challenge differentially altered cytokine and chemokine levels in the serum versus the brain. Within the brain, the cytokine and chemokine response varied between strains, sexes, and days post-challenge. Main findings included differences in T helper (Th) type cytokine responses in various brain regions, particularly the cortex, with respect to IL-4, IL-10, and IL-17 levels. Additionally, peripheral immune challenge altered GFAP and IBA-1 immunoreactivity in the brain in a strain- and sex-dependent manner. Conclusions: These findings indicate that genetic background and sex influence the CNS response to an acute peripheral immune challenge during early postnatal development. Additionally, these data reinforce that the developmental time point during which the challenge occurs has a distinct effect on the activation of CNS-resident cells.

Original languageEnglish (US)
Article number200
JournalJournal of Neuroinflammation
Volume16
Issue number1
DOIs
StatePublished - Oct 31 2019

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Neuroglia
Cytokines
Brain
Chemokines
Central Nervous System
Viral Structures
Interleukin-17
Peripheral Nervous System
Microglia
Serum
Astrocytes
Interleukin-4
Interleukin-10
Hippocampus
Analysis of Variance
Regression Analysis

Keywords

  • Astrocytes
  • Cytokines
  • Microglia
  • Neuroimmune
  • Neuroinflammation
  • Peripheral immune challenge
  • Rat model
  • Sex differences

ASJC Scopus subject areas

  • Neuroscience(all)
  • Immunology
  • Neurology
  • Cellular and Molecular Neuroscience

Cite this

Acute peripheral immune activation alters cytokine expression and glial activation in the early postnatal rat brain. / Bruce, Matthew; Streifel, Karin M.; Boosalis, Casey A.; Heuer, Luke; González, Eduardo A.; Li, Shuyang; Harvey, Danielle J.; Lein, Pamela J.; Van De Water, Judy.

In: Journal of Neuroinflammation, Vol. 16, No. 1, 200, 31.10.2019.

Research output: Contribution to journalArticle

Bruce, Matthew ; Streifel, Karin M. ; Boosalis, Casey A. ; Heuer, Luke ; González, Eduardo A. ; Li, Shuyang ; Harvey, Danielle J. ; Lein, Pamela J. ; Van De Water, Judy. / Acute peripheral immune activation alters cytokine expression and glial activation in the early postnatal rat brain. In: Journal of Neuroinflammation. 2019 ; Vol. 16, No. 1.
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abstract = "Background: Neuroinflammation can modulate brain development; however, the influence of an acute peripheral immune challenge on neuroinflammatory responses in the early postnatal brain is not well characterized. To address this gap in knowledge, we evaluated the peripheral and central nervous system (CNS) immune responses to a mixed immune challenge in early postnatal rats of varying strains and sex. Methods: On postnatal day 10 (P10), male and female Lewis and Brown Norway rats were injected intramuscularly with either a mix of bacterial and viral components in adjuvant, adjuvant-only, or saline. Immune responses were evaluated at 2 and 5 days post-challenge. Cytokine and chemokine levels were evaluated in serum and in multiple brain regions using a Luminex multiplex assay. Multi-factor ANOVAs were used to compare analyte levels across treatment groups within strain, sex, and day of sample collection. Numbers and activation status of astrocytes and microglia were also analyzed in the cortex and hippocampus by quantifying immunoreactivity for GFAP, IBA-1, and CD68 in fixed brain slices. Immunohistochemical data were analyzed using a mixed-model regression analysis. Results: Acute peripheral immune challenge differentially altered cytokine and chemokine levels in the serum versus the brain. Within the brain, the cytokine and chemokine response varied between strains, sexes, and days post-challenge. Main findings included differences in T helper (Th) type cytokine responses in various brain regions, particularly the cortex, with respect to IL-4, IL-10, and IL-17 levels. Additionally, peripheral immune challenge altered GFAP and IBA-1 immunoreactivity in the brain in a strain- and sex-dependent manner. Conclusions: These findings indicate that genetic background and sex influence the CNS response to an acute peripheral immune challenge during early postnatal development. Additionally, these data reinforce that the developmental time point during which the challenge occurs has a distinct effect on the activation of CNS-resident cells.",
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AU - Bruce, Matthew

AU - Streifel, Karin M.

AU - Boosalis, Casey A.

AU - Heuer, Luke

AU - González, Eduardo A.

AU - Li, Shuyang

AU - Harvey, Danielle J.

AU - Lein, Pamela J.

AU - Van De Water, Judy

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AB - Background: Neuroinflammation can modulate brain development; however, the influence of an acute peripheral immune challenge on neuroinflammatory responses in the early postnatal brain is not well characterized. To address this gap in knowledge, we evaluated the peripheral and central nervous system (CNS) immune responses to a mixed immune challenge in early postnatal rats of varying strains and sex. Methods: On postnatal day 10 (P10), male and female Lewis and Brown Norway rats were injected intramuscularly with either a mix of bacterial and viral components in adjuvant, adjuvant-only, or saline. Immune responses were evaluated at 2 and 5 days post-challenge. Cytokine and chemokine levels were evaluated in serum and in multiple brain regions using a Luminex multiplex assay. Multi-factor ANOVAs were used to compare analyte levels across treatment groups within strain, sex, and day of sample collection. Numbers and activation status of astrocytes and microglia were also analyzed in the cortex and hippocampus by quantifying immunoreactivity for GFAP, IBA-1, and CD68 in fixed brain slices. Immunohistochemical data were analyzed using a mixed-model regression analysis. Results: Acute peripheral immune challenge differentially altered cytokine and chemokine levels in the serum versus the brain. Within the brain, the cytokine and chemokine response varied between strains, sexes, and days post-challenge. Main findings included differences in T helper (Th) type cytokine responses in various brain regions, particularly the cortex, with respect to IL-4, IL-10, and IL-17 levels. Additionally, peripheral immune challenge altered GFAP and IBA-1 immunoreactivity in the brain in a strain- and sex-dependent manner. Conclusions: These findings indicate that genetic background and sex influence the CNS response to an acute peripheral immune challenge during early postnatal development. Additionally, these data reinforce that the developmental time point during which the challenge occurs has a distinct effect on the activation of CNS-resident cells.

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KW - Rat model

KW - Sex differences

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