ICAM-1 and VCAM-1 expression following aneurysmal subarachnoid hemorrhage and their possible role in the pathophysiology of subsequent ischemic deficits

BACKGROUND: The pathophysiology of ischemic cerebral lesions following aneurysmal subarachnoid hemorrhage (SAH) is poorly understood. There is growing evidence that inflammatory reactions could be involved in the pathogenesis of such delayed occurring ischemic lesions. The aim of this study was to evaluate adhesion molecules with regard to these lesions following SAH. METHODS: Serum and cerebrospinal fluid (CSF) samples were taken daily from 15 patients up to day 9 after SAH and evaluated for intercellular adhesion molecule-1 (ICAM-1) and vascular adhesion molecule-1 (VCAM-1). RESULTS: CSF and serum samples correlated well during nearly the whole time course (p < 0.0001). A secondary increase in ICAM-1 and VCAM-1 in the serum and CSF correlated with an increase in flow velocity in the transcranial Doppler (p > 0.0001 and p < 0.007) but not to a delayed lesion in the CT scan. CONCLUSION: We believe that inflammatory processes are involved in the pathogenesis of cerebral vasospasm but they might only be a part of a multifactorial pathogenesis.     

Circulating,soluble adhesion proteins in cerebrospinal fluid and serum of patients with multiple sclerosis: Correlation with clinical activity

Soluble adhesion protein intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and endothelial leukocyte adhesion molecule (E-selectin) were measured in serum and cerebrospinal fluid (CSF) of patients with relapsing-remitting multiple sclerosis (RRMS) in remission and in exacerbation, as well as patients with chronic progressive MS, stable MS, and in patients with other neurological and inflammatory diseases (ONDs). Serum ICAM-1 and E-selectin were significantly elevated in patients with MS over those with ONDs and controls. CSF VCAM-1 and E-selectin were found to be elevated over control and disease control samples. No increase in CSF ICAM-1 was observed. Results were analyzed longitudinally and by MS category. In paired CSF and serum samples from patients in exacerbation, elevated VCAM-1 correlated with increased serum VCAM-1 in 5 of 7 patients. Elevated CSF E-selectin did not correlate with elevations in serum E-selectin.     

Differential effects of moderate or heavy alcohol consumption on circulating adhesion molecule levels

Epidemiological studies suggest that moderate but not heavy alcohol consumption provides protection against coronary heart disease. We assessed the relationship between alcohol consumption and serum levels of adhesion molecules involved in the pathogenesis of early atherosclerosis. One-hundred apparently healthy men with similar cardiovascular risk factors were divided into four groups according to ethanol intake. Moderate drinkers (20-40 g/day) showed lower serum intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) levels than abstainers (p < 0.05; both), as well as lower serum ICAM-1, VCAM-1 and E-selectin levels than heavy drinkers (p = 0.01; all). The latter also showed higher serum ICAM-1 and E-selectin levels than abstainers (p < 0.001; both). We conclude that moderate drinkers show a significant reduction of soluble endothelial adhesion molecule levels compared to abstainers and heavy drinkers, that may contribute to the protective effect of moderate alcohol consumption against atherosclerosis.     

Temporal variations of adhesion molecules and matrix metalloproteinases in the course of MS

Thirty patients with clinically isolated syndromes (CIS) were evaluated at the onset of neurological symptoms and when they developed clinically definite MS (CDMS). Surface expression of LFA-1, VLA-4 and intercellular adhesion molecule-1 (ICAM-1) on PBMC and CSF cells was evaluated using flow cytometry. Serum and CSF concentrations of soluble vascular cell adhesion molecules-1 (VCAM-1), ICAM-1 and E-Selectin, as well as MMP-9 and MMP-2 serum concentrations were assayed using ELISA. Surface expression of LFA-1 and VLA-4 molecules on peripheral blood and CSF T cells and monocytes from CIS and CDMS was significantly increased compared with control subjects. Moreover, LFA-1 and VLA-4 expression was significantly higher in patients who developed CDMS compared with those with CIS. Similar changes were observed in the serum levels of MMP-9. Furthermore, patients with CIS and CDMS had significantly higher levels of CSF sVCAM and s-E-Selectin than control subjects. These data suggest that VLA-4, LFA-1 and MMP-9 play a leading role in the evolution of inflammatory demyelinating lesions in patients with CIS who develop CDMS.     

细胞间粘附分子-1在蛛网膜下腔出血后痉挛血管内的表达

目的：研究细胞间粘附分子－1（ICAM－1）在蛛网膜下腔出血（SAH）后脑血管壁内的表达变化规律及其与脑血管痉挛（CVS）的关系。方法：应用免疫组织化学及逆转录－聚合酶链式反应（RT－PCR）等方法，检测大鼠2次注血SAH模型基底动脉壁内ICAM－1在蛋白质和mRNA水平上的表达。结果：在大鼠脑池内注血后第3d，基底动脉血管腔狭窄已非常明显，第5d达到高峰。注血后第1d,ICAM-1表达开始上调，主要在内膜及内膜下，第3dg表达明显增强并持续到第5d。ICAM－1在蛋白和mRNA水平上表达基本一致，且在时程上的变化与CVS的程度密切相关。结论：由ICAM－1介导的血管壁炎症反应可能在CVS发生和发展过程中起重要作用。     

Endothelin-1 levels in plasma and cerebrospinal fluidfollowing subarachnoid haemorrhage

A serial measurement of endothelin-1(ET-1) levels in plasma, cisternal and ventricular cerebrospinal fluid(CSF) was performed in 16 patients with subarachnoid haemorrhage (SAH). The patients were classified as grade III or IV according to the clinical grade of Hunt and Hess, and computerised tomography(CT) was classified as Fisher's CT group 3. Cisternal and ventricular CSF and plasma were obtained from the patients on the day of operation days 0-3, days 5-8 and days 14-18 after SAH. ET-I concentration in each sample was quantified by sandwich-enzyme immunoassay. ET-I levels in plasma and CSF were the highest between days 0-3 and then decreased. The ET-I levels in the cisternal CSF were significantly higher during days 0-3(p<0. 01) and days 5-8(p<0. 01) than those in the ventricular CSF It is suggested that ET-I could play an important role in the early stages of the cerebral vasospasm.     

Endothelin and aneurysmal subarachnoid haemorrhage: a study of subarachnoid cisternal cerebrospinal fluid.

Endothelin (ET) is considered one of the most potent vasoconstrictor polypeptides; several experimental studies have suggested its possible role in the pathogenesis of arterial vasospasm after subarachnoid haemorrhage (SAH). Previously reported data on plasma and CSF levels of endothelin in patients with a diagnosis of SAH have been controversial. Cisternal endothelin CSF levels and the possibility that they could be related to vasospasm and other clinical patterns of SAH were investigated. CSF samples were obtained from 55 patients admitted after angiographic diagnosis of intracranial aneurysm. Levels of ET-1 and ET-3 were measured through radio-immunoassay technique. Twelve patients who had operations for unruptured aneurysms were considered control cases; 43 patients with SAH were classified according to: Hunt and Hess grading at admission, vasospasm grading, CT classification and timing of surgery. In all 55 patients ET-1 was measured, while positive levels of ET-3 were found only in 17 cases of 48. No linear correlation was found between cisternal CSF ET-1 levels when considering time of surgery, CT classification, Hunt and Hess grading at admission, and vasospasm grading. The results of ET-3 assay should be considered with great caution because of the low percentage of positive cases. Cisternal CSF levels of ET-1 and ET-3 are not directly related to the occurrence of arterial vasospasm after the aneurysm rupture, or to other major clinical patterns of SAH; however, ET-1 expression occurs either in paraphysiological (unruptured aneurysm) or in pathological conditions (SAH). It is suggested that ET may potentiate, or may be potentiated by, other factors playing a consistent pathophysiological role in the development of vasospasm.     

NF-κB拮抗剂对大鼠蛛网膜下腔出血后脑血管痉挛的影响

目的应用核因子-κB(NF-κB)拮抗剂治疗大鼠蛛网膜下腔出血(SAH)后脑血管痉挛(CVS),观察大鼠脑基底动脉的病理变化及其管壁上细胞间粘附因子-1(ICAM-1)、白介素-6(IL-6)在治疗前、后的变化。方法 SD大鼠随机分为正常组、SAH组、治疗组及生理盐水组,HE染色观察基底动脉管径的变化;免疫组化染色和原位杂交法检测大鼠脑基底动脉管壁上ICAM-1、IL-6的表达变化。结果治疗组基底动脉管壁增厚程度及管腔狭窄程度有所改善;免疫组化染色显示SAH组IL-6、ICAM-1的表达强烈,原位杂交显示在SAH后,IL-6、ICAM-1的mRNA表达水平上调。经NF-κB拮抗剂二硫代氨基甲酸吡咯烷(PDTC)治疗后,IL-6和ICAM-1的mRNA表达水平均明显减弱(P<0.05)。结论 NF-κB拮抗剂能够抑制SAH后CVS的免疫炎症反应。应用NF-κB拮抗剂对防治CVS有一定效果。     

蛛网膜下腔出血患者血清、脑脊液白细胞介素-6水平研究

目的探讨蛛网膜下腔出血(SAH)后血清、脑脊液(CSF)白细胞介素-6(IL-6)水平变化及临床意义.方法用放免法检测32例不同病因、不同时期、不同病情SAH患者血清及CSF中IL-6水平变化,并与对照组比较.结果SAH后血清及CSF中IL-6水平比对照组明显升高(P＜0.05).CSF中IL-6水平比血清中高,IL-6升高与病情轻重和出血量多少有关.结论IL-6可作为观察病情及迟发性脑血管痉挛(CCVS)的指标.     

Adhesion molecules in multiple sclerosis: relation to subtypes of disease and methylprednisolone therapy

OBJECTIVES: To determine levels of adhesion molecules in blood and cerebrospinal fluid (CSF) samples from patients with different subtypes and activities of multiple sclerosis (MS) and to assess the effect of intravenous methylprednisolone sodium succinate treatment on the levels of soluble adhesion molecules. DESIGN: The expressions of very late activation antigen 4 (VLA-4), lymphocyte function associated antigen 1 (LFA-1), vascular cell adhesion molecule 1 (VCAM-1), and intercellular adhesion molecule 1 (ICAM-1) were determined immunocytochemically, and levels of soluble VCAM-1, ICAM-1, and E-selectin, by means of enzyme immunoassay technique. The volumes of T2- and T1-weighted MS plaques and brain atrophy were determined by means of the semiautomatic magnetic resonance imaging (MRI) segmentation technique. SETTING: A university hospital in Finland. PATIENTS: One hundred subjects (71 patients with MS and 29 healthy control subjects). The subtypes of MS were relapsing-remitting (RRMS [n = 26]), secondary progressive (SPMS [n = 20]), and primary progressive (PPMS [n = 25]). RESULTS: In patients with RRMS and SPMS, the expressions of VLA-4 and LFA-1 on immune cells from blood were at least 1.5- to 3-fold higher than in controls (RRMS, P = .002 and P<.001, respectively; SPMS, P = .03 and P =.001, respectively). In RRMS, LFA-1 and ICAM-1 expression in blood was more up-regulated than in SPMS (P = .03 and P = .01, respectively). The expressions of adhesion molecules on CSF lymphocytes in RRMS and SPMS were of similar magnitude, but the proportions of CSF VLA-4- and LFA-1-expressing lymphocytes were 3- to 4-fold higher than in controls (P = .04 and P = .008, respectively). The levels of serum soluble VCAM-1 were higher in SPMS than in RRMS (P = .005) or PPMS (P = .04). Intravenous methylprednisolone treatment of patients with RRMS in exacerbation caused a significant reduction in the serum levels of soluble VCAM-1 and E-selectin (P<.001). In SPMS, the volumes of T2-weighted plaques correlated with the serum level of soluble ICAM-1 (r = 0.64; P = .03). CONCLUSIONS: Up-regulated adhesion molecules in blood and CSF indicate sustained potential for inflammation in the CNS throughout the clinical spectrum of MS. Therapies interfering with cell adhesion may be of key importance in suppressing MS.     

Regional and temporal expression patterns of interleukin-10, interleukin-10 receptor and adhesion molecules in the rat spinal cord during chronic relapsing EAE

Adhesion molecules intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) mediate leukocyte infiltration into the CNS, in experimental autoimmune encephalomyelitis (EAE) and multiple sclerosis (MS). Because exogenous interleukin-10 (IL-10) inhibits ICAM-1 and VCAM-1 expression and clinical EAE, we hypothesize that endogenous IL-10 signaling may suppress expression of adhesion molecules. In a rat model of chronic relapsing EAE, expression levels of IL-10 and its receptor (IL-10R1), ICAM-1 and VCAM-1 mRNA in the spinal cord are markedly increased, whereas levels of IL-10 mRNA remain relatively low. The temporal pattern of mRNA and protein expression showed marked differences between spinal cord levels. During relapse, IL-10, IL-10R1, ICAM-1, VCAM-1 mRNA levels and neurological scores show positive correlations. We conclude that endogenous IL-10 is not a crucial factor inhibiting adhesion molecule expression in this model.     

A study on cisternal CSF levels of arachidonic acid metabolites after aneurysmal subarachnoid hemorrhage

Arachidonic acid (AA) metabolites may play an important role in the pathogenesis of cerebral vasospasm which complicate subarachnoid hemorrhage. Authors have studied levels of 4 major AA metabolites in lumbar CSF samples and in CSF collected from perianeurismatic cisterns of 40 patients admitted with diagnosis of subarachnoid hemorrhage. Lumbar levels of AA metabolites are significantly higher in SAH patients than in control cases; moreover, cisternal CSF levels of PGD2, TxB2 and LTC4 are significantly higher than lumbar levels. Cisternal CSF levels (expressed in pg/ml +/- SEM) are in the "spasm" group: PGD2: 1129.62 +/- 146.33; 6-keto-PGF1 alpha: 214.2 +/- 19.96; TxB2: 4350.25 +/- 656.87; LTC4: 2582.19 +/- 381.83. In the "no spasm" group: PGD2 460.1 +/- 55.89; 6-keto-PGF1 alpha: 306.37 +/- 88.74; TxB2: 5752.5 +/- 899.25; LTC4: 812.92 +/- 142.06. Statistical analysis (paired t-test) shows values significantly higher for cisternal levels of PGD2 (P less than 0.005) and LTC4 (P less than 0.005) in patients presenting vasospasm. This suggests the importance of the subarachnoidal clot as a source of vasoactive compounds. Higher levels of leukotriene C4 in patients presenting vasospasm suggest a role for the compound in the genesis of local inflammatory processes and morphological changes of the arterial wall.     

Leukocyte-endothelial cell interactions in chronic vasospasm after subarachnoid hemorrhage

Leukocyte-endothelial cell interactions appear to be the root cause of chronic vasospasm after aneurysmal subarachnoid hemorrhage (aSAH). Early clinical observations and indirect experimental evidence suggested an association between inflammation and chronic vasospasm. Early clinical observations in patients with post-hemorrhagic vasospasm included pyrexia, leukocytosis and the presence of circulating immune complexes. Inflammatory infiltrates and increased levels of immunoglobulins and complement fractions within spastic cerebral arteries also provided early evidence for an inflammatory mechanism underlying chronic vasospasm. Early indirect experimental evidence included the ability to reproduce chronic vasospasm with the introduction of inflammatory agents into the subarachnoid space and the inhibition of vasospasm with anti-inflammatory agents. Currently, however, there is an increasing body of direct molecular evidence that demonstrates the pivotal role of leukocyte-endothelial cell interactions in the development of chronic vasospasm. Cell adhesion molecules such as intercellular adhesion molecule-1 (ICAM-1), lymphocyte function-associated antigen-1 (LFA-1), macrophage antigen-1 (Mac-1) and endothelial (E)-selectin mediate interactions between circulating leukocytes and cerebral endothelium. Following aSAH, ICAM-1 is up-regulated in cerebral endothelial cells and along with other cell adhesion molecules, can be detected in the serum and cerebrospinal fluid (CSF) of patients with post-hemorrhagic vasospasm. Monoclonal antibody blocking experiments have demonstrated that the prevention of leukocyte extravasation into the subarachnoid space prevents chronic vasospasm. Similarly, drugs like ibuprofen, which prevent ICAM-1 up-regulation and transendothelial cell migration of leukocytes, prevent vasospasm. In this review, we highlight early observations that suggested an association between inflammation and post-hemorrhagic vasospasm, detail the role of leukocyte-endothelial cell interactions in the development of chronic vasospasm and discuss therapeutic implications of an inflammatory etiology of post-hemorrhagic cerebral vasospasm.     

Potential contribution of nuclear factor-kappaB to cerebral vasospasm after experimental subarachnoid hemorrhage in rabbits.

Nuclear factor-kappaB (NF-kappaB) plays a key role in inflammation, which is involved in the development of cerebral vasospasm after subarachnoid hemorrhage (SAH). In the present study, we assessed the potential role of NF-kappaB in regulation of cerebral vasospasm. Nuclear factor-kappaB DNA-binding activity was measured in cultured vascular smooth muscle cells (VSMCs) treated with hemolysate and pyrrolidine dithiocarbamate (PDTC, 80 micromol/L), an inhibitor of NF-kappaB. Forty-two rabbits were divided into three groups: control, SAH, and PDTC groups (n=14 for each group). The caliber of the basilar artery was evaluated. Nuclear factor-kappaB DNA-binding activity and the gene expression levels of cytokines and adhesion molecules in the basilar artery were measured. Immunohistochemical study was performed to assess the expression and localization of tumor necrosis factor (TNF)-alpha, intercellular adhesion molecule (ICAM)-1, and myeloperoxidase (MPO). It was observed that NF-kappaB DNA-binding activity was significantly increased by treatment with hemolysate in cultured VSCMs, but this increase was suppressed by pretreatment with PDTC. Severe vasospasm was observed in the SAH group, which was attenuated in the PDTC group. Subarachnoid hemorrhage could induce increases of NF-kappaB DNA-binding activity and the gene expression levels of TNF-alpha, interleukin (IL)-1 beta, ICAM-1, and vascular cell adhesion molecule (VCAM)-1, which were reduced in the PDTC group. Immunohistochemical study demonstrated that the expression levels of TNF-alpha, ICAM-1, and MPO were all increased in the SAH group, but these increases were attenuated in the PDTC group. Our results suggest that NF-kappaB is activated in the arterial wall after SAH, which potentially leads to vasospasm development through induction of inflammatory response.     

Arachidonate metabolites and vasospasm after subarachnoid haemorrhage

A wide literature exists about the pathogenesis of cerebral arterial spasm following subarachnoid haemorrhage: several compounds have been identified in human cerebrospinal fluid as possible vasoactive agents involved in the biochemical mechanism of vasospasm onset. Many experimental evidences exist for a major involvement of arachidonate metabolites. The present work represents a review of experimental data supporting the hypothesis of cerebral arterial spasm as a result of an imbalanced vascular regulatory mechanism involving arachidonate metabolites. The authors have also monitored, in 25 cases of aneurysmal subarachnoid haemorrhage, lumbar and cisternal CSF levels of prostacyclin and PGD2, as representative of vasodilating and, respectively, vasoconstrictor compounds. In all cases CSF arachidonate metabolite levels after SAH were significantly higher than in control cases. Ten patients presented with symptomatic vasospasm: lumbar CSF PGD2 levels show fluctuations with superimposed peaks related to the neurological deterioration due to vasospasm, while lumbar CSF prostacyclin concentration-trend suggest a decreasing synthesis. In 15 patients presenting without vasospasm, lumbar CSF concentration of arachidonate metabolites are in a 'steady-state'. These data confirm the existence of an imbalanced biochemical situation promoting vasospasm, markedly in cisterns near to the ruptured aneurysmal wall. The evaluation of cisternal CSF levels of arachidonate metabolites supports the hypothesis of the clotting phenomenon around the ruptured aneurysm as an important predictive pattern of vasospasm, as shown in CT findings.     

Leukocyte-endothelial cell interactions in chronic vasospasm after subarachnoid hemorrhage

Abstract

Leukocyte-endothelial cell interactions appear to be the root cause of chronic vasospasm after aneurysmal subarachnoid hemorrhage (aSAH). Early clinical observations and indirect experimental evidence suggested an association between inflammation and chronic vasospasm. Early clinical observations in patients with post-hemorrhagic vasospasm included pyrexia, leukocytosis and the presence of circulating immune complexes. Inflammatory infiltrates and increased levels of immunoglobulins and complement fractions within spastic cerebral arteries also provided early evidence for an inflammatory mechanism underlying chronic vasospasm. Early indirect experimental evidence included the ability to reproduce chronic vasospasm with the introduction of inflammatory agents into the subarachnoid space and the inhibition of vasospasm with anti-inflammatory agents. Currently, however, there is an increasing body of direct molecular evidence that demonstrates the pivotal role of leukocyte-endothelial cell interactions in the development of chronic vasospasm. Cell adhesion molecules such as intercellular adhesion molecule-1 (ICAM-1), lymphocyte function-associated antigen-1 (LFA-1), macrophage antigen-1 (Mac-1) and endothelial (E)-selectin mediate interactions between circulating leukocytes and cerebral endothelium. Following aSAH, ICAM-1 is up-regulated in cerebral endothelial cells and along with other cell adhesion molecules, can be detected in the serum and cerebrospinal fluid (CSF) of patients with post-hemorrhagic vasospasm. Monoclonal antibody blocking experiments have demonstrated that the prevention of leukocyte extravasation into the subarachnoid space prevents chronic vasospasm. Similarly, drugs like ibuprofen, which prevent ICAM-1 up-regulation and transendothelial cell migration of leukocytes, prevent vasospasm. In this review, we highlight early observations that suggested an association between inflammation and post-hemorrhagic vasospasm, detail the role of leukocyte-endothelial cell interactions in the development of chronic vasospasm and discuss therapeutic implications of an inflammatory etiology of post-hemorrhagic cerebral vasospasm.     

Soluble adhesion molecules in Gilles de la Tourette's syndrome

To investigate the immune-mediated response in TS, and its relationship with streptococcal infection, we measured serum levels of soluble intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) and E-selectin in patients with TS, compared to healthy and diseased controls. Soluble VCAM-1 and sE-selectin were significantly elevated in children and adults with TS, and sVCAM-1 was higher among anti-basal ganglia antibodies (ABGA)-positive adults with TS. No correlation of adhesion molecule levels to clinical severity or anti-streptococcal antibodies was observed. Children with Sydenham's chorea and paediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS) showed an increased level of sICAM-1, but not sVCAM-1 and sE-selectin. These results provide initial evidence for a role of adhesion molecules and systemic inflammation in TS, and support the hypothesis of an ongoing immune-mediated process in this condition.     

亚低温治疗对蛛网膜下腔出血继发性血管痉挛及脑脊液和血浆内皮素、降钙素基因相关肽的影响

目的 探讨亚低温治疗对蛛网膜下腔出血(SAH)继发性血管痉挛及脑脊液和血浆内皮素(ET)、降钙素基因相关肽(CGRP)水平的影响.方法 56例SAH患者随机分成亚低温组和对照组,两组在常规治疗的基础上,亚低温组增加局部亚低温治疗;检测两组入院时及治疗7 d、14 d脑脊液和血浆ET、CGRP水平,并比较两组脑血管痉挛的发病情况.结果 (1)脑脊液、血浆ET水平治疗7 d时亚低温组较对照组显著降低(均P＜0.05);14 d时差异更显著(均P＜0.01);两组CGRP水平治疗第7 d时降至最低,后渐升高,亚低温组较对照组变化幅度小,差异有统计学意义(P＜0.05～0.01).(2)亚低温组脑血管痉挛发病率为6.67%,较对照组的30.77%明显减少(P＜0.05).结论 亚低温治疗减少了SAH患者脑脊液和血浆中ET水平上升幅度及CGRP水平下降幅度,从而降低脑血管痉挛的发生率.     

Arachidonate metabolites and vasospasm after subarachnoid haemorrhage

A wide literature exists about the pathogenesis of cerebral arterial spasm following subarachnoid haemorrhage: several compounds have been identified in human cerebrospinal fluid as possible vasoactive agents involved in the biochemical mechanism of vasospasm onset. Many experimental evidences exist for a major involvement of arachidonate metabolites. The present work represents a review of experimental data supporting the hypothesis of cerebral arterial spasm as a result of an imbalanced vascular regulatory mechanism involving arachidonate metabolites. The authors have also monitored, in 25 cases of aneurysmal subarachnoid haemorrhage, lumbar and cisternal CSF levels of prostacyclin and PGD₂, as representative of vasodilating and, respectively, vasoconstrictor compounds. In all cases CSF arachidonate metabolite levels after SAH were significantly higher than in control cases. Ten patients presented with symptomatic vasospasm: lumbar CSF PGD₂ levels show fluctuations with superimposed peaks related to the neurological deterioration due to vasospasm, while lumbar CSF prostacyclin concentration-trend suggest a decreasing synthesis. In 15 patients presenting without vasospasm, lumbar CSF concentration of arachidonate metabolites are in a 'steady-state'. These data confirm the existence of an imbalanced biochemical situation promoting vasospasrn, markedly in cisterns near to the ruptured aneurysmal wall. The evaluation of cisternal CSF levels of arachidonate metabolites supports the hypothesis of the clotting phenomenon around the ruptured aneurysm as an important predictive pattern of vasospasm, as shown in CT findings.     

Vascular cell adhesion molecule-1 modulation by tumor necrosis factor in experimental allergic encephalomyelitis

Anti-tumor necrosis factor (TNF) antibodies inhibit passively transferred experimental allergic encephalomyelitis (EAE) in SJL mice. The possibility that this occurs through interference in TNF's upregulation of endothelial cell adhesion molecules was investigated. Expression of both vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1) on spinal cord vessels increased during EAE. The upregulation of VCAM-1 was markedly reduced or prevented by anti-TNF treatment. Leukocytic infiltration was 15-fold lower in anti-TNF-treated than diseased animals. Spinal cord endothelial expression of VCAM-1, though not ICAM-1 or fibronectin, positively correlated with the extent of T cell, B cell or monocyte infiltration in each animal.