Traumatic brain injury induces long-lasting changes in immune and regenerative signaling
| Autor: | Mala Sinha, Margaret A. Parsley, Karen E. O. Torres, Ian J. Bolding, Michael T. Falduto, Harris A. Weisz, Helen L. Hellmich, Hannah E. Willey, Donald S. Prough, Kathea M. Johnson, Douglas S. DeWitt, Deborah R. Boone, Heidi Spratt |
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| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Male Critical Care and Emergency Medicine Traumatic Brain Injury Microarrays Physiology Complement System Poison control Gene Expression Hippocampus Biochemistry Rats Sprague-Dawley 0302 clinical medicine Immune Physiology Brain Injuries Traumatic Medicine and Health Sciences Trauma Medicine Regulation of gene expression Principal Component Analysis Multidisciplinary Immune System Proteins Toll-Like Receptors NF-kappa B Brain NFAT Neurodegenerative Diseases Bioassays and Physiological Analysis Medicine Signal transduction Anatomy Traumatic Injury Research Article Signal Transduction Traumatic brain injury Science Inflammatory Diseases Immunology Research and Analysis Methods Real-Time Polymerase Chain Reaction 03 medical and health sciences Immune system Gene Types medicine Genetics Animals Gene Regulation Innate immune system NFATC Transcription Factors business.industry Gene Expression Profiling Biology and Life Sciences Proteins Computational Biology Complement System Proteins medicine.disease Gene expression profiling 030104 developmental biology Gene Expression Regulation Immune System Proteostasis Regulator Genes business Neuroscience Neurotrauma 030217 neurology & neurosurgery Acute-Phase Proteins |
| Zdroj: | PLoS ONE PLoS ONE, Vol 14, Iss 4, p e0214741 (2019) |
| ISSN: | 1932-6203 |
| Popis: | 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-κB 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. |
| Databáze: | OpenAIRE |
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