scholarly journals Inhibitory Effect on Cerebral Inflammatory Response following Traumatic Brain Injury in Rats: A Potential Neuroprotective Mechanism of N-Acetylcysteine

2008 ◽  
Vol 2008 ◽  
pp. 1-8 ◽  
Author(s):  
Gang Chen ◽  
Jixin Shi ◽  
Zhigang Hu ◽  
Chunhua Hang
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Inflammatory Response ◽  
Interleukin 1 ◽  
Inhibitory Effect ◽  
Intercellular Adhesion Molecule ◽  
Secondary Brain Injury ◽  
Intercellular Adhesion Molecule 1 ◽  
Injured Brain ◽  
Inflammatory Proteins

Although N-acetylcysteine (NAC) has been shown to be neuroprotective for traumatic brain injury (TBI), the mechanisms for this beneficial effect are still poorly understood. Cerebral inflammation plays an important role in the pathogenesis of secondary brain injury after TBI. However, it has not been investigated whether NAC modulates TBI-induced cerebral inflammatory response. In this work, we investigated the effect of NAC administration on cortical expressions of nuclear factor kappa B (NF-κB) and inflammatory proteins such as interleukin-1β(IL-1β), tumor necrosis factor-α(TNF-α), interleukin-6 (IL-6), and intercellular adhesion molecule-1 (ICAM-1) after TBI. As a result, we found that NF-κB, proinflammatory cytokines, and ICAM-1 were increased in all injured animals. In animals given NAC post-TBI, NF-κB, IL-1β, TNF-α, and ICAM-1 were decreased in comparison to vehicle-treated animals. Measures of IL-6 showed no change after NAC treatment. NAC administration reduced brain edema, BBB permeability, and apoptotic index in the injured brain. The results suggest that post-TBI NAC administration may attenuate inflammatory response in the injured rat brain, and this may be one mechanism by which NAC ameliorates secondary brain damage following TBI.

scholarly journals Influence of Glutamine on Intestinal Inflammatory Response, Mucosa Structure Alterations and Apoptosis following Traumatic Brain Injury in Rats

2007 ◽  
Vol 35 (5) ◽  
pp. 644-656 ◽  
Author(s):  
D Feng ◽  
W Xu ◽  
G Chen ◽  
C Hang ◽  
H Gao ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Inflammatory Response ◽  
Intestinal Inflammation ◽  
Glutamine Supplementation ◽  
Intercellular Adhesion Molecule ◽  
Intercellular Adhesion Molecule 1 ◽  
Tissue Samples ◽  
Weight Drop ◽  
Factor Α

Traumatic brain injury (TBI) can induce a persistent inflammatory response, histopathological changes and apoptosis in the intestine. Glutamine has been shown to reduce bacterial translocation and maintain intestine mucosal integrity, but its effects on the inflammatory response, structural alterations and apoptosis in intestinal mucosa following TBI have not been previously investigated. Using the weight-drop method, a right parietal cortical contusion was induced in rats and, for the next 5 days, they were fed either chow alone or chow mixed with glutamine. Intestinal tissue samples were then removed for analysis. Following TBI, glutamine supplementation was found to: decrease intestinal concentrations of interleukin (IL) −1β, tumour necrosis factor-α (TNF-α) and IL-6; downregulate intercellular adhesion molecule-1 (ICAM-1) expression; attenuate TBI-induced damage to the intestine structure; and reduce apoptosis. These results suggest that post-TBI glutamine administration could suppress intestinal inflammation, protect intestinal mucosal structure and reduce mucosal apoptosis.

scholarly journals Disruption of Nrf2 Enhances Upregulation of Nuclear Factor-κB Activity, Proinflammatory Cytokines, and Intercellular Adhesion Molecule-1 in the Brain after Traumatic Brain Injury

2008 ◽  
Vol 2008 ◽  
pp. 1-7 ◽  
Author(s):  
Wei Jin ◽  
Handong Wang ◽  
Wei Yan ◽  
Lizhi Xu ◽  
Xiaoliang Wang ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Adhesion Molecule ◽  
Proinflammatory Cytokine ◽  
Intercellular Adhesion ◽  
Intercellular Adhesion Molecule ◽  
Secondary Brain Injury ◽  
Nuclear Factor ◽  
Wild Type ◽  
Intercellular Adhesion Molecule 1

Inflammatory response plays an important role in the pathogenesis of secondary brain injury after traumatic brain injury (TBI). Nuclear factor erythroid 2-related factor 2 (Nrf2) is a key transcription factor that plays a crucial role in cytoprotection against inflammation. The present study investigated the role of Nrf2 in the cerebral upregulation of NF-κB activity, proinflammatory cytokine, and ICAM-1 after TBI. Wild-type Nrf2 (+/+) and Nrf2 (−/−)-deficient mice were subjected to a moderately severe weight-drop impact head injury. Electrophoretic mobility shift assays (EMSAs) were performed to analyze the activation of nuclear factor kappa B (NF-κB). Enzyme-linked immunosorbent assays were performed to quantify the production of tumor necrosis factor-α(TNF-α), interleukin-1β(IL-1β), and interleukin-6 (IL-6). Immunohistochemistry staining experiments were performed to detect the expression of intercellular adhesion molecule-1 (ICAM-1). Nrf2 (−/−) mice were shown to have more NF-κB activation, inflammatory cytokines TNF-α, IL-1βand IL-6 production, and ICAM-1 expression in brain after TBI compared with their wild-type Nrf2 (+/+) counterparts. The results suggest that Nrf2 plays an important protective role in limiting the cerebral upregulation of NF-κB activity, proinflammatory cytokine, and ICAM-1 after TBI.

scholarly journals HMGB1 a-Box Reverses Brain Edema and Deterioration of Neurological Function in a Traumatic Brain Injury Mouse Model

2018 ◽  
Vol 46 (6) ◽  
pp. 2532-2542 ◽  
Author(s):  
Lijun Yang ◽  
Feng Wang ◽  
Liang Yang ◽  
Yunchao Yuan ◽  
Yan Chen ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Brain Edema ◽  
Therapeutic Potential ◽  
High Mobility ◽  
Neurological Injury ◽  
Secondary Brain Injury ◽  
Cell Degeneration ◽  
Injured Brain ◽  
Walking Tests

Background/Aims: Traumatic brain injury (TBI) is a complex neurological injury in young adults lacking effective treatment. Emerging evidences suggest that inflammation contributes to the secondary brain injury following TBI, including breakdown of the blood brain barrier (BBB), subsequent edema and neurological deterioration. High mobility group box-1 (HMGB1) has been identified as a key cytokine in the inflammation reaction following TBI. Here, we investigated the therapeutic efficacy of HMGB1 A-box fragment, an antagonist competing with full-length HMGB1 for receptor binding, against TBI. Methods: TBI was induced by controlled cortical impact (CCI) in adult male mice. HMGB1 A-box fragment was given intravenously at 2 mg/kg/day for 3 days after CCI. HMGB1 A-box-treated CCI mice were compared with saline-treated CCI mice and sham mice in terms of BBB disruption evaluated by Evan’s blue extravasation, brain edema by brain water content, cell death by propidium iodide staining, inflammation by Western blot and ELISA assay for cytokine productions, as well as neurological functions by the modified Neurological Severity Score, wire grip and beam walking tests. Results: HMGB1 A-box reversed brain damages in the mice following TBI. It significantly reduced brain edema by protecting integrity of the BBB, ameliorated cell degeneration, and decreased expression of pro-inflammatory cytokines released in injured brain after TBI. These cellular and molecular effects were accompanied by improved behavioral performance in TBI mice. Notably, HMGB1 A-box blocked IL-1β-induced HMGB1 release, and preferentially attenuated TLR4, Myd88 and P65 in astrocyte cultures. Conclusion: Our data suggest that HMGB1 is involved in CCI-induced TBI, which can be inhibited by HMGB1 A-box fragment. Therefore, HMGB1 A-box fragment may have therapeutic potential for the secondary brain damages in TBI.

scholarly journals Reduced brain edema after traumatic brain injury in mice deficient in P-selectin and intercellular adhesion molecule-1

2000 ◽  
Vol 67 (2) ◽  
pp. 160-168 ◽  
Author(s):  
Michael J. Whalen ◽  
Timothy M. Carlos ◽  
C. Edward Dixon ◽  
Paul Robichaud ◽  
Robert S. B. Clark ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Brain Edema ◽  
Adhesion Molecule ◽  
Intercellular Adhesion ◽  
Intercellular Adhesion Molecule ◽  
Intercellular Adhesion Molecule 1

scholarly journals Antibodies against human neutrophil LECAM-1 (LAM-1/Leu-8/DREG-56 antigen) and endothelial cell ELAM-1 inhibit a common CD18-independent adhesion pathway in vitro

Blood ◽  
1991 ◽  
Vol 78 (3) ◽  
pp. 805-811 ◽  
Author(s):  
TK Kishimoto ◽  
RA Warnock ◽  
MA Jutila ◽  
EC Butcher ◽  
C Lane ◽  
...  
Keyword(s):  
Adhesion Molecule ◽  
Leukocyte Adhesion ◽  
Umbilical Vein ◽  
Interleukin 1 ◽  
Inhibitory Effect ◽  
Neutrophil Function ◽  
Intercellular Adhesion Molecule ◽  
Lymphocyte Function ◽  
Intercellular Adhesion Molecule 1

Neutrophil adhesion to interleukin-1 (IL-1)-stimulated human umbilical vein endothelial cells (HUVEC) involves the CD18 family of leukocyte integrins (lymphocyte function-associated antigen-1 [LFA-1], Mac-1, and p150,95) and LECAM-1 (DREG-56/LEU-8/LAM-1 antigen) on neutrophils and intercellular adhesion molecule-1 (ICAM-1) and endothelial leukocyte adhesion molecule-1 (ELAM-1) on the endothelium. In this study, we compare CD18-independent adhesion pathways mediated by neutrophil LECAM- 1 and endothelial ELAM-1 and find that these two pathways overlap in a variety of assays: (1) anti-LECAM-1 and anti-ELAM-1 monoclonal antibody (MoAb) inhibit neutrophil binding to HUVEC, and the inhibitory effect is not additive; (2) anti-LECAM-1 MoAb, like anti-ELAM-1 MoAb, inhibits neutrophil binding to HUVEC stimulated for 3 hours with IL-1, but not to HUVEC stimulated for 8 hours, by which time ELAM-1 expression is downregulated; (3) anti-ELAM-1 MoAb has no effect on transendothelial migration, a CD18-dependent, LECAM-1-independent neutrophil function. Interestingly, anti-ELAM MoAb has a reduced but significant inhibitory effect on the adhesion of activated neutrophils that have shed their cell-surface LECAM-1. We also show that neutrophil binding to ELAM-1- transfected L cells is inhibited not only by anti-ELAM-1 but also by anti-LECAM-1 MoAb. These results suggest that LECAM-1 and ELAM-1 can operate in the same adhesion pathway, possibly as a receptor- counterreceptor pair. LECAM-1 and ELAM-1 are likely to interact with other ligands as well, perhaps through carbohydrate determinants that modify more than one glycoprotein.

scholarly journals Antibodies against human neutrophil LECAM-1 (LAM-1/Leu-8/DREG-56 antigen) and endothelial cell ELAM-1 inhibit a common CD18-independent adhesion pathway in vitro

Blood ◽  
1991 ◽  
Vol 78 (3) ◽  
pp. 805-811 ◽  
Author(s):  
TK Kishimoto ◽  
RA Warnock ◽  
MA Jutila ◽  
EC Butcher ◽  
C Lane ◽  
...  
Keyword(s):  
Adhesion Molecule ◽  
Leukocyte Adhesion ◽  
Umbilical Vein ◽  
Interleukin 1 ◽  
Inhibitory Effect ◽  
Neutrophil Function ◽  
Intercellular Adhesion Molecule ◽  
Lymphocyte Function ◽  
Intercellular Adhesion Molecule 1

Abstract Neutrophil adhesion to interleukin-1 (IL-1)-stimulated human umbilical vein endothelial cells (HUVEC) involves the CD18 family of leukocyte integrins (lymphocyte function-associated antigen-1 [LFA-1], Mac-1, and p150,95) and LECAM-1 (DREG-56/LEU-8/LAM-1 antigen) on neutrophils and intercellular adhesion molecule-1 (ICAM-1) and endothelial leukocyte adhesion molecule-1 (ELAM-1) on the endothelium. In this study, we compare CD18-independent adhesion pathways mediated by neutrophil LECAM- 1 and endothelial ELAM-1 and find that these two pathways overlap in a variety of assays: (1) anti-LECAM-1 and anti-ELAM-1 monoclonal antibody (MoAb) inhibit neutrophil binding to HUVEC, and the inhibitory effect is not additive; (2) anti-LECAM-1 MoAb, like anti-ELAM-1 MoAb, inhibits neutrophil binding to HUVEC stimulated for 3 hours with IL-1, but not to HUVEC stimulated for 8 hours, by which time ELAM-1 expression is downregulated; (3) anti-ELAM-1 MoAb has no effect on transendothelial migration, a CD18-dependent, LECAM-1-independent neutrophil function. Interestingly, anti-ELAM MoAb has a reduced but significant inhibitory effect on the adhesion of activated neutrophils that have shed their cell-surface LECAM-1. We also show that neutrophil binding to ELAM-1- transfected L cells is inhibited not only by anti-ELAM-1 but also by anti-LECAM-1 MoAb. These results suggest that LECAM-1 and ELAM-1 can operate in the same adhesion pathway, possibly as a receptor- counterreceptor pair. LECAM-1 and ELAM-1 are likely to interact with other ligands as well, perhaps through carbohydrate determinants that modify more than one glycoprotein.

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