Long-Term Upregulation of Inflammation and Suppression of Cell Proliferation in the Brain of Adult Rats Exposed to Traumatic Brain Injury Using the Controlled Cortical Impact Model

Authors

Sandra A. Acosta, University of South FloridaFollow
Naoki Tajiri, University of South FloridaFollow
Kazutaka Shinozuka, University of South Florida
Hiroto Ishikawa, University of South Florida
Bethany Grimmig, University of South Florida
David M. Diamond, University of South FloridaFollow
Paul R. Sanberg, University of South FloridaFollow
Paula C. Bickford, University of South FloridaFollow
Yuji Kaneko, University of South FloridaFollow
Cesario V. Borlongan, University of South FloridaFollow

Document Type

Article

Publication Date

1-3-2013

Keywords

Animals, Brain, Brain Injuries, Brain Mapping, Cell Death, Cell Differentiation, Cell Proliferation, Disease Models, Animal, Gene Expression Regulation, Genes, MHC Class II, Immunohistochemistry, Inflammation, Male, Microglia, Neurogenesis, Rats, Rats, Sprague-Dawley, Up-Regulation

Digital Object Identifier (DOI)

https://doi.org/10.1371/journal.pone.0053376

Abstract

The long-term consequences of traumatic brain injury (TBI), specifically the detrimental effects of inflammation on the neurogenic niches, are not very well understood. In the present in vivo study, we examined the prolonged pathological outcomes of experimental TBI in different parts of the rat brain with special emphasis on inflammation and neurogenesis. Sixty days after moderate controlled cortical impact injury, adult Sprague-Dawley male rats were euthanized and brain tissues harvested. Antibodies against the activated microglial marker, OX6, the cell cycle-regulating protein marker, Ki67, and the immature neuronal marker, doublecortin, DCX, were used to estimate microglial activation, cell proliferation, and neuronal differentiation, respectively, in the subventricular zone (SVZ), subgranular zone (SGZ), striatum, thalamus, and cerebral peduncle. Stereology-based analyses revealed significant exacerbation of OX6-positive activated microglial cells in the striatum, thalamus, and cerebral peduncle. In parallel, significant decrements in Ki67-positive proliferating cells in SVZ and SGZ, but only trends of reduced DCX-positive immature neuronal cells in SVZ and SGZ were detected relative to sham control group. These results indicate a progressive deterioration of the TBI brain over time characterized by elevated inflammation and suppressed neurogenesis. Therapeutic intervention at the chronic stage of TBI may confer abrogation of these deleterious cell death processes.

Rights Information

This work is licensed under a Creative Commons Attribution 4.0 License.

Was this content written or created while at USF?

Yes

Citation / Publisher Attribution

PLoS One, v. 8, issue 1, art. e53376, p. 1-8

Scholar Commons Citation

Acosta, Sandra A.; Tajiri, Naoki; Shinozuka, Kazutaka; Ishikawa, Hiroto; Grimmig, Bethany; Diamond, David M.; Sanberg, Paul R.; Bickford, Paula C.; Kaneko, Yuji; and Borlongan, Cesario V., "Long-Term Upregulation of Inflammation and Suppression of Cell Proliferation in the Brain of Adult Rats Exposed to Traumatic Brain Injury Using the Controlled Cortical Impact Model" (2013). Psychology Faculty Publications. 1375.
https://digitalcommons.usf.edu/psy_facpub/1375