Neuroinflammation after Traumatic Brain Injury Is Enhanced in Activating Transcription Factor 3 Mutant Mice

Journal of Neurotrauma
Philip FörstnerBernd Knöll

Abstract

Traumatic brain injury (TBI) induces a neuroinflammatory response resulting in astrocyte and microglia activation at the lesion site. This involves upregulation of neuroinflammatory genes, including chemokines and interleukins. However, so far, there is lack of knowledge on transcription factors (TFs) modulating this TBI-associated gene expression response. Herein, we analyzed activating transcription factor 3 (ATF3), a TF encoding a regeneration-associated gene (RAG) predominantly studied in peripheral nervous system (PNS) injury. ATF3 contributes to PNS axon regeneration and was shown before to regulate inflammatory processes in other injury models. In contrast to PNS injury, data on ATF3 in central nervous system (CNS) injury are sparse. We used Atf3 mouse mutants and a closed-head weight-drop-based TBI model in adult mice to target the rostrolateral cortex resulting in moderate injury severity. Post-TBI, ATF3 was upregulated already at early time points (i.e,. 1-4 h) post-injury in the brain. Mortality and weight loss upon TBI were slightly elevated in Atf3 mutants. ATF3 deficiency enhanced TBI-induced paresis and hematoma formation, suggesting that ATF3 limits these injury outcomes in wild-type mice. Next, we analyzed TBI-...Continue Reading

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Citations

Jan 22, 2019·Journal of Neurotrauma·Colleen N BodnarAdam D Bachstetter
Jan 14, 2020·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Philip Förstner, Bernd Knöll
Jul 10, 2018·Cerebral Cortex·Akila ChandrasekarFrancesco Roselli
Dec 17, 2020·Neuropsychiatric Disease and Treatment·Fei NiuMing Sun
Jul 3, 2021·International Journal of Molecular Sciences·Shotaro Michinaga, Yutaka Koyama

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GraphPad Prism
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