Dexamethasone inhibits ICAM-1 and MMP-9 expression and reduces brain edema in intracerebral hemorrhagic rats

Yang, Jen-Tsung; Lee, Tsong‐Hai; Lee, I‐Neng; Chung, Chiu-Yen; Kuo, Chia-Hui; Weng, Hsu–Huei

doi:10.1007/s00701-011-1122-2

Cited by 46 publications

(39 citation statements)

References 32 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The mechanism by which neutrophils, macrophages and lymphocytes enter the brain after ICH has received much less attention. Several studies have shown an upregulation of intercellular adhesion molecule-1 (ICAM-1) after experimental ICH [92,101,104] and Rolland et al . found that fingolimod blocked both ICAM-1 upregulation and lymphocyte transmigration into brain [101].…”

Section: Introductionmentioning

confidence: 99%

Vascular disruption and blood–brain barrier dysfunction in intracerebral hemorrhage

Keep

Zhou

Xiang

et al. 2014

Fluids Barriers CNS

175

156

View full text Add to dashboard Cite

This article reviews current knowledge of the mechanisms underlying the initial hemorrhage and secondary blood–brain barrier (BBB) dysfunction in primary spontaneous intracerebral hemorrhage (ICH) in adults. Multiple etiologies are associated with ICH, for example, hypertension, Alzheimer’s disease, vascular malformations and coagulopathies (genetic or drug-induced). After the initial bleed, there can be continued bleeding over the first 24 hours, so-called hematoma expansion, which is associated with adverse outcomes. A number of clinical trials are focused on trying to limit such expansion. Significant progress has been made on the causes of BBB dysfunction after ICH at the molecular and cell signaling level. Blood components (e.g. thrombin, hemoglobin, iron) and the inflammatory response to those components play a large role in ICH-induced BBB dysfunction. There are current clinical trials of minimally invasive hematoma removal and iron chelation which may limit such dysfunction. Understanding the mechanisms underlying the initial hemorrhage and secondary BBB dysfunction in ICH is vital for developing methods to prevent and treat this devastating form of stroke.

show abstract

Section: Introductionmentioning

confidence: 99%

Vascular disruption and blood–brain barrier dysfunction in intracerebral hemorrhage

Keep

Zhou

Xiang

et al. 2014

Fluids Barriers CNS

175

156

View full text Add to dashboard Cite

show abstract

“…Patients treated with fingolimod have a higher Glasgow Coma Scale score, lower National Institutes of Health Stroke Scale score, improved neurologic function and fewer ICH-related lung infections without differences in the occurrence of adverse events when compared with the control group. Dexamethasone can promote the recovery of ICH injury by inhibiting the inflammatory response and reduce brain edema because of its capacity to decrease apoptotic cell death and inhibiting the intercellular adhesion molecule-1 and MMP-9 expression [10,84] .…”

Section: Inhibition Of Pmns Infiltration and Microglia Activationmentioning

confidence: 99%

Mechanism and Therapy of Brain Edema after Intracerebral Hemorrhage

et al. 2016

View full text Add to dashboard Cite

Background: Intracerebral hemorrhage (ICH) is a subtype of stroke with a severe high mortality and disability rate and accounts for about 10-15% of all strokes. The oppression and destruction by hematoma to brain tissue cause the primary brain injury. The inflammation and coagulation response after ICH would accelerate the formation of brain edema around hematoma, resulting in a more severe and durable injury. Currently, treatments for ICH are focusing on the primary injury including reducing intracranial hypertension, blood pressure control, and rehabilitation. There is a short-of-effective medical treatment for secondary inflammation and reducing brain edema in ICH patients. So, it is very important to study on the relationship between brain edema and ICH. Summary: Many molecular and cellular mechanisms contribute to the formation and progress of brain edema after ICH; inhibition of brain edema provides favorable outcome of ICH. Key Messages: This review mainly discusses the pathology and mechanism of brain edema, the effects of brain edema on ICH, and the methods of treating brain edema after ICH.

show abstract

“…Interestingly, dexamethasone used to attenuate brain edema in the clinic downregulated VEGF and MMP-9 levels in vitro and in vivo experimental models. 17,71) Thus, the anti-edema effects of dexamethasone may involve ameliorating BBB disruption that is commonly observed in TBI, cerebral ischemia, and hemorrhage, and which leads to lethal conditions including brain edema, severe inflammatory damage, and hemorrhage. Thus, protection of the BBB must be a beneficial strategy for these pathophysiological conditions and a broad spectrum of brain damage.…”

Section: Discussionmentioning

confidence: 99%

“…The expressions of CAMs and chemokines evaluated after brain damage were reported to accelerate leukocyte infiltration. [15][16][17] Infiltrating leukocytes migrate into areas of damage and release various cytokines, chemokines, reactive oxygen species (ROS) and proteases that cause brain tissue damage.…”

Section: Inflammationmentioning

confidence: 99%

Protection of the Blood–Brain Barrier as a Therapeutic Strategy for Brain Damage

Michinaga

Kōyama

2017

Biological & Pharmaceutical Bulletin

View full text Add to dashboard Cite

Severe brain damage by trauma, ischemia, and hemorrhage lead to fatal conditions including sudden death, subsequent complications of the extremities and cognitive dysfunctions. Despite the urgent need for treatments for these complications, currently available therapeutic drugs are limited. Blood-brain barrier (BBB) disruption is a common pathogenic feature in many types of brain damage. The characteristic pathophysiological conditions caused by BBB disruption are brain edema resulting from an excessive increase of brain water content, inflammatory damage caused by infiltrating immune cells, and hemorrhage caused by the breakdown of microvessel structures. Because these pathogenic features induced by BBB disruption cause fatal conditions, their improvement is a desirable strategy. Many studies using experimental animal models have focused on molecules involved in BBB disruption, including vascular endothelial growth factors (VEGFs), matrix metalloproteinases (MMPs) and endothelins (ETs). The inhibition of these factors in several experimental animals was protective against BBB disruption caused by several types of brain damage, and ameliorated brain edema, inflammatory damage, and hemorrhagic transformation. In patients with brain damage, the up-regulation of these factors was observed and was related to brain damage severity. Thus, BBB protection by targeting VEGFs, MMPs, and ETs might be a novel strategy for the treatment of brain damage.

show abstract

Dexamethasone inhibits ICAM-1 and MMP-9 expression and reduces brain edema in intracerebral hemorrhagic rats

Abstract: In conclusion, these data show that DEX successfully reduced post-stroke brain edema by decreasing MMP-9 and ICAM-1 levels, partially through the IκB/NF-κB signaling pathway. The timing of DEX administration in relation to the onset of brain injury may be critical.

Cited by 46 publications

References 32 publications

Vascular disruption and blood–brain barrier dysfunction in intracerebral hemorrhage

Vascular disruption and blood–brain barrier dysfunction in intracerebral hemorrhage

Mechanism and Therapy of Brain Edema after Intracerebral Hemorrhage

Protection of the Blood–Brain Barrier as a Therapeutic Strategy for Brain Damage

Contact Info

Product

Resources

About