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A Preclinical Controlled Cortical Impact Model for Traumatic Hemorrhage Contusion and Neuroinflammation
Published on: June 10, 2020
Acute, regional inflammatory response after traumatic brain injury: Implications for cellular therapy
Matthew T Harting1, Fernando Jimenez, Sasha D Adams
1Department of Pediatric Surgery, University of Texas Medical School at Houston and Children's Memorial Hermann Hospital, Houston, Texas 77030, USA.
The acute traumatic brain injury (TBI) environment is highly inflammatory, especially near the injury site. This inflammation may impact the effectiveness of early cellular therapies for TBI.
Area of Science:
- Neuroscience
- Immunology
- Regenerative Medicine
Background:
- Cellular therapy shows potential for traumatic brain injury (TBI).
- Understanding the brain's environment after TBI is crucial for optimizing cell therapy.
- The acute inflammatory response post-TBI is not well characterized.
Purpose of the Study:
- To characterize the acute, regional inflammatory response following TBI.
- To investigate the impact of the TBI microenvironment on immune cells.
Main Methods:
- Controlled cortical impact (CCI) model in rats.
- Intracerebral fluid and tissue collection from different brain regions at various time points.
- Cytokine level measurement, polymorphonuclear cell (PMN) assays, and immunohistochemistry for CD68+ cells.
Main Results:
- Elevated pro-inflammatory cytokines (IL-1α, IL-1β, IL-6, TNF-α) in injury and penumbral regions within 48 hours post-TBI.
- Increased PMN expression of CD11b and L-selectin after incubation with injury/penumbral fluid.
- CD68+ cells (microglia/macrophages) observed in direct injury and penumbral areas.
Conclusions:
- The early cerebral environment after TBI is significantly pro-inflammatory, particularly near the injury site.
- This acute inflammatory milieu could be a target for early cell therapy.
- Conversely, the inflammatory environment might hinder the efficacy of early cellular therapies.
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