Low cerebral blood flow is a non-invasive biomarker of neuroinflammation after repetitive mild traumatic brain injury

Sitara B. Sankar; Alyssa F. Pybus; Amanda Liew; Bharat Sanders; Kajol J. Shah; Levi B. Wood; Erin M. Buckley

Neurobiology of Disease (Apr 2019)

Low cerebral blood flow is a non-invasive biomarker of neuroinflammation after repetitive mild traumatic brain injury

Sitara B. Sankar,
Alyssa F. Pybus,
Amanda Liew,
Bharat Sanders,
Kajol J. Shah,
Levi B. Wood,
Erin M. Buckley

Affiliations

Sitara B. Sankar: Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, USA; Parker H. Petit Institute for Bioengineering and Bioscience, Georgia Institute of Technology, USA
Alyssa F. Pybus: Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, USA; Parker H. Petit Institute for Bioengineering and Bioscience, Georgia Institute of Technology, USA
Amanda Liew: Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, USA
Bharat Sanders: Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, USA
Kajol J. Shah: Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, USA
Levi B. Wood: Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, USA; Parker H. Petit Institute for Bioengineering and Bioscience, Georgia Institute of Technology, USA; George W. Woodruff School of Mechanical Engineering, Georgia Institute of Technology, USA; Corresponding authors.
Erin M. Buckley: Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, USA; Department of Pediatrics, School of Medicine, Emory University, USA; Corresponding authors.

Journal volume & issue: Vol. 124
pp. 544 – 554

Abstract

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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.

Published in Neurobiology of Disease

ISSN: 0969-9961 (Print); 1095-953X (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Medicine: Internal medicine: Neurosciences. Biological psychiatry. Neuropsychiatry
Website: https://www.journals.elsevier.com/neurobiology-of-disease

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