Microglia Adopt Longitudinal Transcriptional Changes After Traumatic Brain Injury

Hadijat M. Makinde, Talia B. Just, Gaurav T. Gadhvi, Deborah Rachelle Winter, Steven J Schwulst*

*Corresponding author for this work

Research output: Contribution to journalArticle

Abstract

Background: Traumatic brain injury (TBI) is an under-recognized public health threat. Even mild brain injuries can lead to long-term neurologic impairment. Microglia play a fundamental role in the development and progression of this ensuing neurologic impairment. Despite this, a microglia-specific injury signature has yet to be identified. We hypothesized that TBI would lead to long-term changes in the transcriptional profile of microglial pathways associated with the development of subsequent neurologic impairment. Materials and methods: Male C57BL/6 mice underwent TBI via a controlled cortical impact and were followed longitudinally. FACSorted microglia from TBI mice were subjected to Quantiseq 3′-biased RNA sequencing at 7, 30, and 90 d after TBI. K-means clustering on 396 differentially expressed genes was performed, and gene ontology enrichment analysis was used to determine corresponding enriched processes. Results: Differentially expressed genes in microglia exhibited four main patterns of expression over the course of TBI. In particular, we identified four gene clusters which corresponded to the host defense response, synaptic plasticity, lipid remodeling, and membrane polarization. Conclusions: Transcriptional profiling within individual populations of microglia after TBI remains a critical unmet research need within the field of TBI. This focused study identified several physiologic processes within microglia that may be associated with development of long-term neurologic impairment after TBI. These data demonstrate the capability of longitudinal transcriptional profiling to uncover potential cell-specific targets for the treatment of TBI.

Original languageEnglish (US)
Pages (from-to)113-122
Number of pages10
JournalJournal of Surgical Research
Volume246
DOIs
StatePublished - Feb 1 2020

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Microglia
Nervous System
Traumatic Brain Injury
RNA Sequence Analysis
Gene Ontology
Neuronal Plasticity
Membrane Lipids
Multigene Family
Inbred C57BL Mouse
Brain Injuries
Genes
Cluster Analysis
Public Health
Wounds and Injuries

Keywords

  • FACS
  • Microglia
  • RNA Sequencing
  • TBI

ASJC Scopus subject areas

  • Surgery

Cite this

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title = "Microglia Adopt Longitudinal Transcriptional Changes After Traumatic Brain Injury",
abstract = "Background: Traumatic brain injury (TBI) is an under-recognized public health threat. Even mild brain injuries can lead to long-term neurologic impairment. Microglia play a fundamental role in the development and progression of this ensuing neurologic impairment. Despite this, a microglia-specific injury signature has yet to be identified. We hypothesized that TBI would lead to long-term changes in the transcriptional profile of microglial pathways associated with the development of subsequent neurologic impairment. Materials and methods: Male C57BL/6 mice underwent TBI via a controlled cortical impact and were followed longitudinally. FACSorted microglia from TBI mice were subjected to Quantiseq 3′-biased RNA sequencing at 7, 30, and 90 d after TBI. K-means clustering on 396 differentially expressed genes was performed, and gene ontology enrichment analysis was used to determine corresponding enriched processes. Results: Differentially expressed genes in microglia exhibited four main patterns of expression over the course of TBI. In particular, we identified four gene clusters which corresponded to the host defense response, synaptic plasticity, lipid remodeling, and membrane polarization. Conclusions: Transcriptional profiling within individual populations of microglia after TBI remains a critical unmet research need within the field of TBI. This focused study identified several physiologic processes within microglia that may be associated with development of long-term neurologic impairment after TBI. These data demonstrate the capability of longitudinal transcriptional profiling to uncover potential cell-specific targets for the treatment of TBI.",
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Microglia Adopt Longitudinal Transcriptional Changes After Traumatic Brain Injury. / Makinde, Hadijat M.; Just, Talia B.; Gadhvi, Gaurav T.; Winter, Deborah Rachelle; Schwulst, Steven J.

In: Journal of Surgical Research, Vol. 246, 01.02.2020, p. 113-122.

Research output: Contribution to journalArticle

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T1 - Microglia Adopt Longitudinal Transcriptional Changes After Traumatic Brain Injury

AU - Makinde, Hadijat M.

AU - Just, Talia B.

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AU - Winter, Deborah Rachelle

AU - Schwulst, Steven J

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AB - Background: Traumatic brain injury (TBI) is an under-recognized public health threat. Even mild brain injuries can lead to long-term neurologic impairment. Microglia play a fundamental role in the development and progression of this ensuing neurologic impairment. Despite this, a microglia-specific injury signature has yet to be identified. We hypothesized that TBI would lead to long-term changes in the transcriptional profile of microglial pathways associated with the development of subsequent neurologic impairment. Materials and methods: Male C57BL/6 mice underwent TBI via a controlled cortical impact and were followed longitudinally. FACSorted microglia from TBI mice were subjected to Quantiseq 3′-biased RNA sequencing at 7, 30, and 90 d after TBI. K-means clustering on 396 differentially expressed genes was performed, and gene ontology enrichment analysis was used to determine corresponding enriched processes. Results: Differentially expressed genes in microglia exhibited four main patterns of expression over the course of TBI. In particular, we identified four gene clusters which corresponded to the host defense response, synaptic plasticity, lipid remodeling, and membrane polarization. Conclusions: Transcriptional profiling within individual populations of microglia after TBI remains a critical unmet research need within the field of TBI. This focused study identified several physiologic processes within microglia that may be associated with development of long-term neurologic impairment after TBI. These data demonstrate the capability of longitudinal transcriptional profiling to uncover potential cell-specific targets for the treatment of TBI.

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