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Influence of percussion trauma on expression of intercellular adhesion molecule-1 (ICAM-1) by human cerebral
1Department of Surgery, College of Medicine, University of Vermont, Burlington, USA.
Objectives:
Brain injury is associated with the production of oxygen free radicals (OFR) and the accumulation of polymorphonuclear leukocytes (PMN) at the site of injury, both of which may be involved in the evolution of secondary cerebral injury. Intercellular adhesion molecule-1 (ICAM-1) is responsible for adherence of PMNs. We sought to determine whether percussion trauma altered the expression of ICAM-1 and to determine the effect of OFR scavengers on ICAM-1 expression after percussion trauma.
Design:
Prospective controlled laboratory research using passage 2 human cerebral microvascular endothelium (HCME).
Materials And Methods:
Cell lysates were collected over 24 hours and analyzed for ICAM-1 by enzyme-linked immunosorbent assay (ELISA) after trauma or incubation with tumor necrosis factor (TNF)-alpha. OFR scavengers were added immediately after trauma with or without previous incubation with TNF-alpha.
Measurements And Main Results:
Sublethal percussion trauma did not alter ICAM-1 expression by HCME. TNF-alpha upregulated ICAM-1 in percussed and nonpercussed cells with maximal ICAM-1 expression at 24 hours (p < 0.01, ANOVA). However, percussion trauma significantly blunted the response of HCME to TNF-alpha. The addition of OFR scavengers after percussion trauma alone had no effect on ICAM-1 expression at 24 hours, but restored the response of percussed HCME to TNF-alpha.
Conclusions:
Percussion trauma alters the response of HCME to cytokine-induced ICAM-1 upregulation, and the normal response is restored by OFR scavengers. This suggests that HCME become dysfunctional after percussion trauma and this dysfunction may be mediated by OFR.
Insights
Brain injury triggers oxygen free radicals (OFR) and leukocyte buildup. OFR scavengers restored normal Intercellular Adhesion Molecule-1 (ICAM-1) expression in brain cells after trauma, suggesting OFR mediate dysfunction.
Area of Science:
- Neuroscience
- Cell Biology
- Trauma Research
Background:
- Brain injury involves oxygen free radicals (OFR) and polymorphonuclear leukocytes (PMN).
- Intercellular Adhesion Molecule-1 (ICAM-1) mediates PMN adherence.
- Understanding ICAM-1 regulation post-trauma is crucial for secondary injury mitigation.
Purpose of the Study:
- To investigate if percussion trauma alters ICAM-1 expression in human cerebral microvascular endothelium (HCME).
- To determine the effect of OFR scavengers on ICAM-1 expression following percussion trauma.
- To explore the role of OFR in trauma-induced endothelial cell dysfunction.
Main Methods:
- Prospective controlled laboratory study using passage 2 HCME.
- Analysis of ICAM-1 expression via ELISA over 24 hours post-trauma or TNF-alpha stimulation.
- Administration of OFR scavengers immediately after trauma, with or without TNF-alpha.
Main Results:
- Percussion trauma alone did not alter ICAM-1 expression in HCME.
- TNF-alpha upregulated ICAM-1, but trauma blunted this response.
- OFR scavengers restored the blunted TNF-alpha response in traumatized HCME.
Conclusions:
- Percussion trauma impairs HCME response to cytokine-induced ICAM-1 upregulation.
- OFR scavengers normalize the ICAM-1 response, indicating OFR mediation of dysfunction.
- This suggests OFR play a key role in secondary brain injury mechanisms.