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Traumatic brain injury induces long-lasting changes in immune and regenerative signaling.

ABSTRACT: There are no existing treatments for the long-term degenerative effects of traumatic brain injury (TBI). This is due, in part, to our limited understanding of chronic TBI and uncertainty about which proposed mechanisms for long-term neurodegeneration are amenable to treatment with existing or novel drugs. Here, we used microarray and pathway analyses to interrogate TBI-induced gene expression in the rat hippocampus and cortex at several acute, subchronic and chronic intervals (24 hours, 2 weeks, 1, 2, 3, 6 and 12 months) after parasagittal fluid percussion injury. We used Ingenuity pathway analysis (IPA) and Gene Ontology enrichment analysis to identify significantly expressed genes and prominent cell signaling pathways that are dysregulated weeks to months after TBI and potentially amenable to therapeutic modulation. We noted long-term, coordinated changes in expression of genes belonging to canonical pathways associated with the innate immune response (i.e., NF-?B signaling, NFAT signaling, Complement System, Acute Phase Response, Toll-like receptor signaling, and Neuroinflammatory signaling). Bioinformatic analysis suggested that dysregulation of these immune mediators-many are key hub genes-would compromise multiple cell signaling pathways essential for homeostatic brain function, particularly those involved in cell survival and neuroplasticity. Importantly, the temporal profile of beneficial and maladaptive immunoregulatory genes in the weeks to months after the initial TBI suggests wider therapeutic windows than previously indicated.

SUBMITTER: Boone DR

PROVIDER: S-EPMC6447179 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Traumatic brain injury induces long-lasting changes in immune and regenerative signaling.

Boone Deborah R DR Weisz Harris A HA Willey Hannah E HE Torres Karen E O KEO Falduto Michael T MT Sinha Mala M Spratt Heidi H Bolding Ian J IJ Johnson Kathea M KM Parsley Margaret A MA DeWitt Douglas S DS Prough Donald S DS Hellmich Helen L HL

PloS one 20190403 4

There are no existing treatments for the long-term degenerative effects of traumatic brain injury (TBI). This is due, in part, to our limited understanding of chronic TBI and uncertainty about which proposed mechanisms for long-term neurodegeneration are amenable to treatment with existing or novel drugs. Here, we used microarray and pathway analyses to interrogate TBI-induced gene expression in the rat hippocampus and cortex at several acute, subchronic and chronic intervals (24 hours, 2 weeks, ...[more]

PMID: 30943276

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Traumatic brain injury induces long-lasting changes in immune and regenerative signaling.

Publications

Traumatic brain injury induces long-lasting changes in immune and regenerative signaling.

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