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Updated: May 29, 2026
Laser Capture Microdissection of Enriched Populations of Neurons or Single Neurons for Gene Expression Analysis After Traumatic Brain Injury
Published on: April 10, 2013
Dissecting inflammatory complications in critically injured patients by within-patient gene expression changes: a
Keyur H Desai1, Chuen Seng Tan, Jeffrey T Leek
1Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, New Jersey, United States of America.
Background:
Trauma is the number one killer of individuals 1-44 y of age in the United States. The prognosis and treatment of inflammatory complications in critically injured patients continue to be challenging, with a history of failed clinical trials and poorly understood biology. New approaches are therefore needed to improve our ability to diagnose and treat this clinical condition.
Methods And Findings:
We conducted a large-scale study on 168 blunt-force trauma patients over 28 d, measuring ∼400 clinical variables and longitudinally profiling leukocyte gene expression with ∼800 microarrays. Marshall MOF (multiple organ failure) clinical score trajectories were first utilized to organize the patients into five categories of increasingly poor outcomes. We then developed an analysis framework modeling early within-patient expression changes to produce a robust characterization of the genomic response to trauma. A quarter of the genome shows early expression changes associated with longer-term post-injury complications, captured by at least five dynamic co-expression modules of functionally related genes. In particular, early down-regulation of MHC-class II genes and up-regulation of p38 MAPK signaling pathway were found to strongly associate with longer-term post-injury complications, providing discrimination among patient outcomes from expression changes during the 40-80 h window post-injury.
Conclusions:
The genomic characterization provided here substantially expands the scope by which the molecular response to trauma may be characterized and understood. These results may be instrumental in furthering our understanding of the disease process and identifying potential targets for therapeutic intervention. Additionally, the quantitative approach we have introduced is potentially applicable to future genomics studies of rapidly progressing clinical conditions.
Trial Registration:
ClinicalTrials.gov NCT00257231
Insights
Genomic profiling of trauma patients reveals early gene expression changes, like MHC-class II down-regulation, that predict longer-term complications and multiple organ failure (MOF). This advance aids in understanding trauma
Area of Science:
- Genomics
- Trauma Research
- Molecular Biology
Background:
- Trauma is a leading cause of death in young adults in the US.
- Managing inflammatory complications post-trauma remains a significant clinical challenge.
- Existing treatments and diagnostic methods for trauma complications require improvement.
Purpose of the Study:
- To characterize the genomic response to trauma.
- To identify early molecular predictors of post-injury complications.
- To develop a framework for analyzing gene expression changes in trauma patients.
Main Methods:
- Studied 168 blunt-force trauma patients over 28 days.
- Collected approximately 400 clinical variables.
- Performed longitudinal leukocyte gene expression profiling using microarrays.
Main Results:
- Organized patients into five outcome categories based on multiple organ failure (MOF) scores.
- Identified dynamic co-expression modules capturing genomic responses.
- Found early down-regulation of MHC-class II genes and up-regulation of p38 MAPK signaling associated with poor outcomes.
Conclusions:
- Genomic characterization provides a broader understanding of trauma's molecular response.
- Identified potential therapeutic targets for trauma complications.
- The quantitative approach can be applied to other rapidly progressing conditions.
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