ICAM-1 and VCAM-1 Expression following Aneurysmal Subarachnoid Hemorrhage and Their Possible Role in the Pathophysiology of Subsequent Ischemic Deficits

Rothoerl, Ralf Dirk; Schebesch, Karl-Michael; Kubitza, Marion; Woertgen, Chris; Brawanski, Alexander; Pina, Ana-Luisa

doi:10.1159/000093243

Cited by 45 publications

(22 citation statements)

References 53 publications

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“…30 In both SMCs and endothelial cells, VCAM-1 is a potent mediator of inflammatory cell adhesion and found to be upregulated in both experimental aneurysm models 31 as well as in humans after aneurysm rupture. 32 Vascular cell adhesion molecule-1 helps bind key inflammatory cells that lead to further release of matrixremodeling proteins and vessel wall breakdown in aneurysm models. Similarly IL-1b has been found in the vascular media of cerebral aneurysms and IL-1b knockout mice have been associated with decreased incidence of advanced aneurysmal changes and apoptosis through caspase regulation.…”

Section: Discussionmentioning

confidence: 99%

TNF-α Induces Phenotypic Modulation in Cerebral Vascular Smooth Muscle Cells: Implications for Cerebral Aneurysm Pathology

Ali

Starke

Jabbour

et al. 2013

J Cereb Blood Flow Metab

136

107

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Little is known about vascular smooth muscle cell (SMC) phenotypic modulation in the cerebral circulation or pathogenesis of intracranial aneurysms. Tumor necrosis factor-alpha (TNF-a) has been associated with aneurysms, but potential mechanisms are unclear. Cultured rat cerebral SMCs overexpressing myocardin induced expression of key SMC contractile genes (SM-a-actin, SM-22a, smooth muscle myosin heavy chain), while dominant-negative cells suppressed expression. Tumor necrosis factor-alpha treatment inhibited this contractile phenotype and induced pro-inflammatory/matrix-remodeling genes (monocyte chemoattractant protein-1, matrix metalloproteinase-3, matrix metalloproteinase-9, vascular cell adhesion molecule-1, interleukin-1 beta). Tumor necrosis factor-alpha increased expression of KLF4, a known regulator of SMC differentiation. Kruppel-like transcription factor 4 (KLF4) small interfering RNA abrogated TNF-a activation of inflammatory genes and suppression of contractile genes. These mechanisms were confirmed in vivo after exposure of rat carotid arteries to TNF-a and early on in a model of cerebral aneurysm formation. Treatment with the synthesized TNF-a inhibitor 3,6-dithiothalidomide reversed pathologic vessel wall alterations after induced hypertension and hemodynamic stress. Chromatin immunoprecipitation assays in vivo and in vitro demonstrated that TNFa promotes epigenetic changes through KLF4-dependent alterations in promoter regions of myocardin, SMCs, and inflammatory genes. In conclusion, TNF-a induces phenotypic modulation of cerebral SMCs through myocardin and KLF4-regulated pathways. These results demonstrate a novel role for TNF-a in promoting a pro-inflammatory/matrix-remodeling phenotype, which has important implications for the mechanisms behind intracranial aneurysm formation.

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Section: Discussionmentioning

confidence: 99%

TNF-α Induces Phenotypic Modulation in Cerebral Vascular Smooth Muscle Cells: Implications for Cerebral Aneurysm Pathology

Ali

Starke

Jabbour

et al. 2013

J Cereb Blood Flow Metab

136

107

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“…11,55 Several animal studies and clinical series have shown that inflammatory processes contribute to the pathogenesis of cerebral vasospasm. 33,54,57 It is well known that leukocyte trafficking increases in SAH due to a breakdown of the blood-brain barrier. 5,[8][9][10][11]14,23,52,66 Increased levels of various soluble adhesion molecules (such as E-selectin, intercellular adhesion molecule-1, and vascular adhesion molecule-1) and cytokines (such as IL-6 and IL-1) have been noted in the plasma and CSF of patients with SAH.…”

Section: Discussionmentioning

confidence: 99%

Serum and cerebrospinal fluid C-reactive protein levels as predictors of vasospasm in aneurysmal subarachnoid hemorrhage

Fountas¹,

Τάσιου²,

Kapsalaki

et al. 2009

FOC

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Object Cerebral vasospasm is a common and potentially devastating complication of aneurysmal subarachnoid hemorrhage (aSAH). Inflammatory processes seem to play a major role in the pathogenesis of vasospasm. The Creactive protein (CRP) constitutes a highly sensitive inflammatory marker. The association of elevated systemic CRP and coronary vasospasm has been well established. Additionally, elevation of the serum CRP levels has been demonstrated in patients with aSAH. The purpose of the current study was to evaluate the possible relationship between elevated CRP levels in the serum and CSF and the development of vasospasm in patients with aSAH. Methods . A total of 41 adult patients in whom aSAH was diagnosed were included in the study. Their demographics, the admitting Glasgow Coma Scale (GCS) score, Hunt and Hess grade, Fisher grade, CT scans, digital subtraction angiography studies, and daily neurological examinations were recorded. Serial serum and CSF CRP measurements were obtained on Days 0, 1, 2, 3, 5, 7, and 9. All patients underwent either surgical or endovascular treatment within 48 hours of their admission. The outcome was evaluated using the Glasgow Outcome Scale and the modified Rankin Scale. Results The CRP levels in serum and CSF peaked on the 3rd postadmission day, and the CRP levels in CSF were always higher than the serum levels. Patients with lower admission GCS scores and higher Hunt and Hess and Fisher grades had statistically significantly higher levels of CRP in serum and CSF. Patients with angiographic vasospasm had higher CRP measurements in serum and CSF, in a statistically significant fashion (p < 0.0001). Additionally, patients with higher CRP levels in serum and CSF had less favorable outcome in this cohort. Conclusions Patients with aSAH who had high Hunt and Hess and Fisher grades and low GCS scores showed elevated CRP levels in their CSF and serum. Furthermore, patients developing angiographically proven vasospasm demonstrated significantly elevated CRP levels in serum and CSF, and increased CRP measurements were strongly associated with poor clinical outcome in this cohort.

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“…With a modern SAH management, the risk for death and permanent disability from vasospasm decrease for less than 10%, but it is still remains one of the leading causes of preventable poor outcome after rupture of an aneurysm [14][15][16] [17][18][19][20][21][22] .…”

Section: Introductionmentioning

confidence: 99%

C-reactive protein and vasospasm after aneurysmal subarachnoid hemorrhage1

Romero

Catâneo

2014

Acta Cir. Bras.

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PURPOSE: To evaluate the relationship between C reactive protein levels and clinical and radiological parameters with delayed ischemic neurological deficits and outcome after aneurysmal subarachnoid hemorrhage. METHODS:One hundred adult patients with aneurismal SAH were prospectively evaluated. Besides the baseline characteristics, daily C-reactive protein levels were prospectively measured until day 10 after subarachnoid hemorrhage. The primary end point was outcome assessed by Glasgow Outcome Scale, the secondary was the occurrence of delayed ischemic neurological deficits (DINDs). RESULTS:A progressive increase in the CRP levels from the admission to 3rd postictal day was observed, followed by a slow decrease until the 9th day. Hemodynamic changes in TCD were associated with higher serum CRP levels. Patients with lower GCS scores presented with increased CRP levels. Patients with higher Hunt and Hess grades on admission developed significantly higher CRP serum levels. Patients with higher admission Fisher grades showed increased levels of CRP. A statistically significant inverse correlation was established in our series between CRP serum levels and GOS on discharge and CRP levels. CONCLUSIONS:Higher C-reactive protein serum levels are associated with worse clinical outcome and the occurrence of delayed ischemic neurological deficits. Because C-reactive protein levels were significantly elevated in the early phase, they might be a useful parameter to monitor.

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ICAM-1 and VCAM-1 Expression following Aneurysmal Subarachnoid Hemorrhage and Their Possible Role in the Pathophysiology of Subsequent Ischemic Deficits

Cited by 45 publications

References 53 publications

TNF-α Induces Phenotypic Modulation in Cerebral Vascular Smooth Muscle Cells: Implications for Cerebral Aneurysm Pathology

TNF-α Induces Phenotypic Modulation in Cerebral Vascular Smooth Muscle Cells: Implications for Cerebral Aneurysm Pathology

Serum and cerebrospinal fluid C-reactive protein levels as predictors of vasospasm in aneurysmal subarachnoid hemorrhage

C-reactive protein and vasospasm after aneurysmal subarachnoid hemorrhage1

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