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Todd BP, Chimenti MS, Luo Z, et al. Traumatic brain injury results in unique microglial and astrocyte transcriptomes enriched for type I interferon response. J Neuroinflammation. 2021;18(1):151doi: 10.1186/s12974-021-02197-w.
Todd, B. P., Chimenti, M. S., Luo, Z., Ferguson, P. J., Bassuk, A. G., & Newell, E. A. (2021). Traumatic brain injury results in unique microglial and astrocyte transcriptomes enriched for type I interferon response. Journal of neuroinflammation, 18(1), 151. https://doi.org/10.1186/s12974-021-02197-w
Todd, Brittany P, et al. "Traumatic brain injury results in unique microglial and astrocyte transcriptomes enriched for type I interferon response." Journal of neuroinflammation vol. 18,1 (2021): 151. doi: https://doi.org/10.1186/s12974-021-02197-w
Todd BP, Chimenti MS, Luo Z, Ferguson PJ, Bassuk AG, Newell EA. Traumatic brain injury results in unique microglial and astrocyte transcriptomes enriched for type I interferon response. J Neuroinflammation. 2021 Jul 05;18(1):151. doi: 10.1186/s12974-021-02197-w. PMID: 34225752; PMCID: PMC8259035.
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J Neuroinflammation. 2021 Jul 05;18(1):151. doi: 10.1186/s12974-021-02197-w.

Traumatic brain injury results in unique microglial and astrocyte transcriptomes enriched for type I interferon response.

Journal of neuroinflammation

Brittany P Todd, Michael S Chimenti, Zili Luo, Polly J Ferguson, Alexander G Bassuk, Elizabeth A Newell

Affiliations

  1. Medical Scientist Training Program, University of Iowa, Iowa City, IA, USA.
  2. Iowa Institute of Human Genetics, Bioinformatics Division, University of Iowa, Iowa City, IA, USA.
  3. Department of Pediatrics, University of Iowa, Iowa City, IA, USA.
  4. Department of Pediatrics, University of Iowa, Iowa City, IA, USA. [email protected].
  5. Department of Pediatrics, University of Iowa, Iowa City, IA, USA. [email protected].

PMID: 34225752 PMCID: PMC8259035 DOI: 10.1186/s12974-021-02197-w

Abstract

BACKGROUND: Traumatic brain injury (TBI) is a leading cause of death and disability that lacks neuroprotective therapies. Following a TBI, secondary injury response pathways are activated and contribute to ongoing neurodegeneration. Microglia and astrocytes are critical neuroimmune modulators with early and persistent reactivity following a TBI. Although histologic glial reactivity is well established, a precise understanding of microglia and astrocyte function following trauma remains unknown.

METHODS: Adult male C57BL/6J mice underwent either fluid percussion or sham injury. RNA sequencing of concurrently isolated microglia and astrocytes was conducted 7 days post-injury to evaluate cell-type-specific transcriptional responses to TBI. Dual in situ hybridization and immunofluorescence were used to validate the TBI-induced gene expression changes in microglia and astrocytes and to identify spatial orientation of cells expressing these genes. Comparative analysis was performed between our glial transcriptomes and those from prior reports in mild TBI and other neurologic diseases to determine if severe TBI induces unique states of microglial and astrocyte activation.

RESULTS: Our findings revealed sustained, lineage-specific transcriptional changes in both microglia and astrocytes, with microglia showing a greater transcriptional response than astrocytes at this subacute time point. Microglia and astrocytes showed overlapping enrichment for genes related to type I interferon signaling and MHC class I antigen presentation. The microglia and astrocyte transcriptional response to severe TBI was distinct from prior reports in mild TBI and other neurodegenerative and neuroinflammatory diseases.

CONCLUSION: Concurrent lineage-specific analysis revealed novel TBI-specific transcriptional changes; these findings highlight the importance of cell-type-specific analysis of glial reactivity following TBI and may assist with the identification of novel, targeted therapies.

Keywords: Astrocytes; Microglia; Traumatic brain injury; Type I interferon

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