Heparin Attenuates the Expression of TNFα-induced Cerebral Endothelial Cell Adhesion Molecule

Lee, Jehee; Kim, Chul Hoon; Seo, Gi Ho; Lee, Jinu; Kim, Joo Hee; Kim, Dong Goo; Ahn, Young Soo

doi:10.4196/kjpp.2008.12.5.231

Cited by 7 publications

(4 citation statements)

References 38 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In particular, UFH blunts upregulation of surface LEU selectins (L-, E-, and P-selectin), key adhesion molecules responsible for LEU rolling on endothelium in the systemic microcirculation in different animal models. 33 UFH can also inhibit expression of LEU CD18/CD11b 34 and its EC counter-ligands, ICAM-1 and VCAM-1, 35,36 the receptors directly implicated in LEU adhesion to EC. In a cerebral ischemia rat model, heparin was found to inhibit leukocyte accumulation in ischemic tissue, reducing infarction size and improving neurological recovery.…”

Section: Discussionmentioning

confidence: 99%

Unfractionated heparin after TBI reduces in vivo cerebrovascular inflammation, brain edema and accelerates cognitive recovery

Nagata

Kumasaka

Browne

et al. 2016

Journal of Trauma and Acute Care Surgery

View full text Add to dashboard Cite

BACKGROUND Severe traumatic brain injury (TBI) may increase the risk of venous thromboembolic complications; however, early prevention with heparinoids is often withheld for its anticoagulant effect. New evidence suggests low molecular weight heparin reduces cerebral edema and improves neurological recovery after stroke and TBI, through blunting of cerebral leukocyte (LEU) recruitment. It remains unknown if unfractionated heparin (UFH) similarly affects brain inflammation and neurological recovery post-TBI. We hypothesized that UFH after TBI reduces cerebral edema by reducing LEU-mediated inflammation and improves neurological recovery. METHODS CD1 male mice underwent either TBI by controlled cortical impact (CCI) or sham craniotomy. UFH (75 U/kg or 225 U/kg) or vehicle (VEH, 0.9% saline) was administered 2, 11, 20, 27, and 34 hours after TBI. At 48 hours, pial intravital microscopy through a craniotomy was used to visualize live brain LEUs interacting with endothelium and microvascular fluorescein isothiocyanate–albumin leakage. Neurologic function (Garcia Neurological Test, GNT) and body weight loss ratios were evaluated 24 and 48 hours after TBI. Cerebral and lung wet-to-dry ratios were evaluated post mortem. ANOVA with Bonferroni correction was used to determine significance (p < 0.05). RESULTS Compared to positive controls (CCI), both UFH doses reduced post-TBI in vivo LEU rolling on endothelium, concurrent cerebrovascular albumin leakage, and ipsilateral cerebral water content after TBI. Additionally, only low dose UFH (75 U/kg) improved GNT at both 24 and 48 hours after TBI. High dose UFH (225 U/kg) significantly increased body weight loss above sham at 48 hours. Differences in lung water content and blood pressure between groups were not significant. CONCLUSIONS UFH after TBI reduces LEU recruitment, microvascular permeability, and brain edema to injured brain. Lower UFH doses concurrently improve neurological recovery whereas higher UFH may worsen functional recovery. Further study is needed to determine if this is caused by increased bleeding from injured brain with higher UFH doses.

show abstract

Section: Discussionmentioning

confidence: 99%

Unfractionated heparin after TBI reduces in vivo cerebrovascular inflammation, brain edema and accelerates cognitive recovery

Nagata

Kumasaka

Browne

et al. 2016

Journal of Trauma and Acute Care Surgery

View full text Add to dashboard Cite

show abstract

“…Interestingly, gene expression of VCAM-1 detected much higher and earlier than ICAM-1 gene expression. Since initial identification as an endothelial cell surface glycoprotein, previous studies reported ICAM-1 and VCAM-1 expression in nonvascular CNS cells, such as astrocytes, neuroblastoma and glioblastoma [1,2,12,[14][15][16][17][18]. The interaction of astrocytes with endothelial cells in the formation of BBB implies a critical role in the neuroinflammation response [1].…”

Section: Discussionmentioning

confidence: 99%

Lactosylceramide Mediates the Expression of Adhesion Molecules in TNF-α and IFNγ-stimulated Primary Cultured Astrocytes

Lee

Kim

Park

et al. 2011

Korean J Physiol Pharmacol

View full text Add to dashboard Cite

“…Therefore, heparin has direct anti-inflammatory properties [158,159] linked to the binding of proinflammatory factors [160,161]. Heparin has been shown to specifically decrease the number of leukocytes participating in the inflammatory response to any insult occurring within the CNS [162,163]. In fact, UFH is a potent inhibitor of the adhesion molecules such as both leukocytes and endothelial cell selectins [164].…”

Section: Heparin and Sahmentioning

confidence: 99%

Compartmental Cerebrospinal Fluid Events Occurring after Subarachnoid Hemorrhage: An “Heparin Oriented” Systematic Review

Tartara

Montalbetti

Crobeddu

et al. 2023

IJMS

View full text Add to dashboard Cite

Subarachnoid hemorrhage (SAH) represents a severe acute event with high morbidity and mortality due to the development of early brain injury (EBI), secondary delayed cerebral ischemia (DCI), and shunt-related hydrocephalus. Secondary events (SSE) such as neuroinflammation, vasospasm, excitotoxicity, blood-brain barrier disruption, oxidative cascade, and neuronal apoptosis are related to DCI. Despite improvement in management strategies and therapeutic protocols, surviving patients frequently present neurological deficits with neurocognitive impairment. The aim of this paper is to offer to clinicians a practical review of the actually documented pathophysiological events following subarachnoid hemorrhage. To reach our goal we performed a literature review analyzing reported studies regarding the mediators involved in the pathophysiological events following SAH occurring in the cerebrospinal fluid (CSF) (hemoglobin degradation products, platelets, complement, cytokines, chemokines, leucocytes, endothelin-1, NO-synthase, osteopontin, matricellular proteins, blood-brain barrier disruption, microglia polarization). The cascade of pathophysiological events secondary to SAH is very complex and involves several interconnected, but also distinct pathways. The identification of single therapeutical targets or specific pharmacological agents may be a limited strategy able to block only selective pathophysiological paths, but not the global evolution of SAH-related events. We report furthermore on the role of heparin in SAH management and discuss the rationale for use of intrathecal heparin as a pleiotropic therapeutical agent. The combination of the anticoagulant effect and the ability to interfere with SSE theoretically make heparin a very interesting molecule for SAH management.

show abstract

Heparin Attenuates the Expression of TNFα-induced Cerebral Endothelial Cell Adhesion Molecule

Cited by 7 publications

References 38 publications

Unfractionated heparin after TBI reduces in vivo cerebrovascular inflammation, brain edema and accelerates cognitive recovery

Unfractionated heparin after TBI reduces in vivo cerebrovascular inflammation, brain edema and accelerates cognitive recovery

Lactosylceramide Mediates the Expression of Adhesion Molecules in TNF-α and IFNγ-stimulated Primary Cultured Astrocytes

Compartmental Cerebrospinal Fluid Events Occurring after Subarachnoid Hemorrhage: An “Heparin Oriented” Systematic Review

Contact Info

Product

Resources

About