Low cerebral blood flow is a non-invasive biomarker of neuroinflammation after repetitive mild traumatic brain injury.
Cerebral blood flow
Cytokines
Kinase signaling
Mild traumatic brain injury
Neuroinflammation
Journal
Neurobiology of disease
ISSN: 1095-953X
Titre abrégé: Neurobiol Dis
Pays: United States
ID NLM: 9500169
Informations de publication
Date de publication:
04 2019
04 2019
Historique:
received:
13
09
2018
revised:
04
12
2018
accepted:
24
12
2018
pubmed:
29
12
2018
medline:
30
11
2019
entrez:
29
12
2018
Statut:
ppublish
Résumé
Previous work has shown that non-invasive optical measurement of low cerebral blood flow (CBF) is an acute biomarker of poor long-term cognitive outcome after repetitive mild traumatic brain injury (rmTBI). Herein, we explore the relationship between acute cerebral blood flow and underlying neuroinflammation. Specifically, because neuroinflammation is a driver of secondary injury after TBI, we hypothesized that both glial activation and inflammatory signaling are associated with acute CBF and, by extension, with long-term cognitive outcome after rmTBI. To test this hypothesis, cortical CBF was non-invasively measured in anesthetized mice 4 h after 3 repetitive closed head injuries spaced once-daily, at which time brains were collected. Right hemispheres were fixed for immunohistochemical staining for glial activation markers Iba1 and GFAP while left hemispheres were used to quantify Iba1 and GFAP expression via Western blot as well as 32 cytokines and 21 phospho-proteins in the MAPK, PI3K/Akt, and NF-κB pathways using a Luminex multiplexed immunoassay. N = 8/7 injured/sham C57/black-6 adult male mice were studied. Within the injured group, CBF inversely correlated with Iba1 expression (R = -0.86, p < .01). Further, partial least squares regression analysis revealed significant correlations between CBF and expression of multiple pro-inflammatory cytokines, including RANTES and IL-17. Finally, within the injured group, phosphorylation of specific signals in the MAPK and NF-κB intracellular signaling pathways (e.g., p38 MAPK and NF-κB) were significantly positively correlated with Iba1. In total, our data indicate that acute cerebral blood flow after rmTBI is a biomarker of underlying neuroinflammatory pathology.
Identifiants
pubmed: 30592976
pii: S0969-9961(18)30585-0
doi: 10.1016/j.nbd.2018.12.018
pmc: PMC6528169
mid: NIHMS1518951
pii:
doi:
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
544-554Subventions
Organisme : NINDS NIH HHS
ID : R21 NS104801
Pays : United States
Organisme : NIGMS NIH HHS
ID : T32 GM008433
Pays : United States
Informations de copyright
Copyright © 2019 Elsevier Inc. All rights reserved.
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