TY - JOUR
T1 - Repeated mild traumatic brain injury in mice elicits long term innate immune cell alterations in blood, spleen, and brain
AU - Smith, Jared A.
AU - Nguyen, Tyler
AU - Karnik, Sonali
AU - Davis, Brittany C.
AU - Al-Juboori, Mohammed H.
AU - Kacena, Melissa A.
AU - Obukhov, Alexander G.
AU - White, Fletcher A.
N1 - Publisher Copyright:
© 2023 The Authors
PY - 2023/7/15
Y1 - 2023/7/15
N2 - Mild traumatic brain injury is an insidious event whereby the initial injury leads to ongoing secondary neuro- and systemic inflammation through various cellular pathways lasting days to months after injury. Here, we investigated the impact of repeated mild traumatic brain injury (rmTBI) and the resultant systemic immune response in male C57B6 mice using flow cytometric methodology on white blood cells (WBCs) derived from the blood and spleen. Isolated mRNA derived from spleens and brains of rmTBI mice was assayed for changes in gene expression at one day, one week, and one month following the injury paradigm. We observed increases in Ly6C+, Ly6C-, and total monocyte percentages in both blood and spleen at one month after rmTBI. Differential gene expression analysis for the brain and spleen tissues uncovered significant changes in many genes, including csf1r, itgam, cd99, jak1,cd3ε, tnfaip6, and nfil3. Additional analysis revealed alterations in several immune signaling pathways over the course of one month in the brain and spleen of rmTBI mice. Together, these results indicate that rmTBI produces pronounced gene expression changes in the brain and spleen. Furthermore, our data suggest that monocyte populations may reprogram towards the proinflammatory phenotype over extended periods of time after rmTBI.
AB - Mild traumatic brain injury is an insidious event whereby the initial injury leads to ongoing secondary neuro- and systemic inflammation through various cellular pathways lasting days to months after injury. Here, we investigated the impact of repeated mild traumatic brain injury (rmTBI) and the resultant systemic immune response in male C57B6 mice using flow cytometric methodology on white blood cells (WBCs) derived from the blood and spleen. Isolated mRNA derived from spleens and brains of rmTBI mice was assayed for changes in gene expression at one day, one week, and one month following the injury paradigm. We observed increases in Ly6C+, Ly6C-, and total monocyte percentages in both blood and spleen at one month after rmTBI. Differential gene expression analysis for the brain and spleen tissues uncovered significant changes in many genes, including csf1r, itgam, cd99, jak1,cd3ε, tnfaip6, and nfil3. Additional analysis revealed alterations in several immune signaling pathways over the course of one month in the brain and spleen of rmTBI mice. Together, these results indicate that rmTBI produces pronounced gene expression changes in the brain and spleen. Furthermore, our data suggest that monocyte populations may reprogram towards the proinflammatory phenotype over extended periods of time after rmTBI.
KW - Immune dysfunction
KW - Monocyte
KW - mTBI
UR - http://www.scopus.com/inward/record.url?scp=85160362826&partnerID=8YFLogxK
U2 - 10.1016/j.jneuroim.2023.578106
DO - 10.1016/j.jneuroim.2023.578106
M3 - Article
AN - SCOPUS:85160362826
SN - 0165-5728
VL - 380
JO - Journal of Neuroimmunology
JF - Journal of Neuroimmunology
M1 - 578106
ER -