Applicability of the SPAN-100 index in a prospective and contemporary cohort of patients treated with intravenous rtPA in Catalonia. / Aplicabilidad del índice SPAN-100 en una cohorte prospectiva y contemporánea de pacientes tratados con rtPA por vía intravenosa en Cataluña.

BACKGROUND: Prognostic scales can be helpful for selecting patients for reperfusion treatment. This study aims to assess the prognostic ability of the recently published SPAN-100 index in a large cohort of stroke patients treated with intravenous thrombolysis (IV rtPA). METHODS: Using data from the prospective registery of all reperfusion treatments administered in Catalonia, we selected patients treated with IV rtPA alone between 2011 and 2012. The SPAN-100 index was calculated as the sum of age (years) and NIHSS score, and patients in the cohort were classified as SPAN-100 positive [≥ 100] or SPAN-100 negative [< 100]. We measured raw and adjusted rates of symptomatic intracerebral haemorrhage (SICH), mortality, and 3-month functional outcome (mRS 0-2) for each SPAN-100 category. Area under the ROC curve was calculated to predict the main outcome measures. RESULTS: We studied 1685 rtPA-treated patients, of whom 1405 (83%) were SPAN-100 negative. The SICH rates adjusted for sex, pre-stroke mRS, hypertension, diabetes, dyslipidaemia, ischaemic heart disease, heart failure, atrial fibrillation, prior TIA/stroke and time to thrombolysis did not differ between groups, but likelihood of functional independence (mRS 0-2) at 3 months was nearly 8 times higher in the SPAN-100 negative group than in the positive group. Furthermore, the 3-month mortality rate was 5 times higher in the SPAN-100 positive group. ROC curve analysis showed high specificities for predicting both functional independence and 3-month mortality for a cut-off point of 100. CONCLUSION: The SPAN-100 index is a simple and straightforward method that may be useful for selecting candidates for rtPA treatment in doubtful cases, and for informing patients and their relatives about likely outcomes.

Drug resistance and secondary treatment of ischaemic stroke: The genetic component of the response to acetylsalicylic acid and clopidogrel.

INTRODUCTION: Cerebrovascular diseases are among the leading causes of death and disability in developed countries. Acetylsalicylic acid (ASA) and clopidogrel are the most widely-used antiplatelet drugs for secondary prevention of recurrent thromboembolic events. However, there have been cases in which antiplatelet drugs did not inhibit platelet activity; this phenomenon is called resistance, and it may be modulated at the genetic level. DEVELOPMENT: Following a literature search, we reviewed the current state of antiplatelet therapy and covered the different types of resistance to antiplatelet therapy, how it is measured, current problems and limitations, and any genetic factors that have been associated with resistance. We mainly used the Genome Wide Association Studies in the field of ASA and clopidogrel resistance. CONCLUSIONS: We observed an association between different genetic factors and antiplatelet drug resistance as measured by platelet activity. However, there is no evident association between these genetic factors and risk of new thromboembolic events.

Reperfusion therapy in acute ischaemic stroke due to cervical and cerebral artery dissection: Results from a Spanish multicentre study.

INTRODUCTION: Ischaemic stroke (IS) due to cervical and cerebral artery dissection (CAD) is a rare entity, and few data are available on the use of such reperfusion therapies as intravenous fibrinolysis and mechanical thrombectomy in these patients. We analysed the use of these treatments in patients with IS due to CAD and compared them against patients receiving reperfusion treatment for IS of other aetiologies. METHODS: We conducted an observational, retrospective, multicentre study of patients with IS due to CAD recorded in the National Stroke Registry of the Spanish Society of Neurology during the period 2011-2019. Comparative analyses were performed between: a) patients with CAD treated and not treated with reperfusion therapies and b) patients treated with reperfusion for IS due to CAD and patients treated with reperfusion for IS due to other causes. Epidemiological data, stroke variables, and outcomes at discharge and at 3 months were included in the analysis. RESULTS: The study included 21,037 patients with IS: 223 (1%) had IS due to CAD, of whom 68 (30%) received reperfusion treatment. Reperfusion treatments were used less frequently in cases of vertebral artery dissection and more frequently in patients with carotid artery occlusion. Compared to patients with IS due to other causes, patients with CAD were younger, more frequently underwent mechanical thrombectomy, and less frequently received intravenous fibrinolysis. Rates of haemorrhagic complications, mortality, and independence at 3 months were similar in both groups. CONCLUSIONS: Reperfusion therapy is frequently used in patients with IS due to CAD. The outcomes of these patients demonstrate the efficacy and safety of reperfusion treatments, and are comparable to the outcomes of patients with IS due to other aetiologies.

Identification of a 'snapshot' of co-expressed angiogenic markers in laser-dissected vessels from unstable carotid plaques with targeted arrays.

BACKGROUND/AIMS: Angiogenesis is a feature of the atherogenic process, with intimal neovascularisation arising from vessels in the adventitia, adjacent to a plaque. Immature, leaky blood vessels from unstable plaques proliferate abnormally and, being poorly invested with smooth muscle cells, may contribute to instability of the plaque by facilitation of inflammatory cell infiltration and haemorrhagic complications. METHODS: We used laser-capture microdissection to isolate angiogenic areas of the extracellular matrix (containing CD105/flt-1-positive, fragile thin-walled vessels) and non-angiogenic vascular areas (CD105-negative, with smooth muscle cell covering) of complicated endarterectomy plaques, and specifically designed angiogenesis-TaqMan real-time PCR microarrays to identify gene expression. RESULTS: Important pro-angiogenic components, including Notch-3, delta-like-4 (DLL4), Tie-2, angiopoietin-1 (Angio-1) and receptor for advanced glycation end products (RAGE), and one anti-angiogenic factor, endostatin, were up-regulated in these regions. Immunohistochemistry demonstrated localisation within intimal, active (CD105-positive) microvessels and co-localisation of Notch-3 and DLL4/Tie-2 and Angio-1 in the same vessels indicating multiple/synergistic signalling mechanisms associated with vessel development. CONCLUSION: These data, although providing only a snapshot of information, demonstrate that plaque vascularisation occurs in the presence of multiple angiogenically active factors. Knowledge of their combined effects could help in the formulation of novel therapeutics designed to stabilise or prevent their formation in the treatment of atherosclerosis.

Cognitive profile following COVID-19 infection: Clinical predictors leading to neuropsychological impairment.

BACKGROUND: Cognitive manifestations associated with the severity of a novel coronavirus (COVID-19) infection are unknown. An early detection of neuropsychological manifestations could modify the risk of subsequent irreversible impairment and further neurocognitive decline. METHODS: In our single-center cohort study, we included all consecutive adult patients, aged between 20 and 60 years old with confirmed COVID-19 infection. Neuropsychological assessment was performed by the same trained neuropsychologist from April, 22nd through June 16th, 2020. Patients with previous known cognitive impairment, any central nervous system or psychiatric disease were excluded. Demographic, clinical, pharmacological and laboratory data were extracted from medical records. RESULTS: Thirty-five patients met inclusion criteria and were included in the study. Patients presenting headache, anosmia, dysgeusia, diarrhea and those who required oxygen therapy had lower scores in memory, attention and executive function subtests as compared to asymptomatic patients. Patients with headache and clinical hypoxia scored lower in the global Cognitive Index (P â€‹= â€‹0.002, P â€‹= â€‹0.010). A T score lower than 30 was observed in memory domains, attention and semantic fluency (2 [5.7%]) in working memory and mental flexibility (3 [8.6%]) and in phonetic fluency (4 [11.4%]). Higher scores in anxiety and depression (P â€‹= â€‹0.047, P â€‹= â€‹0.008) were found in patients with cognitive complaints. CONCLUSIONS: In our cohort of COVID-19 patients neurologic manifestations were frequent, including cognitive impairment. Neurological symptoms during infection, diarrhea and oxygen therapy were risk factors for neurocognitive impairment. Cognitive complaints were associated with anxiety and depression.

Reperfusion treatment in acute ischaemic stroke due to cervical and cerebral artery dissection: results of a Spanish national multicentre study. / Tratamiento de reperfusión en el ictus isquémico agudo por disección arterial cervicocerebral: descripción de los resultados de un estudio nacional multicéntrico.

INTRODUCTION: Ischaemic stroke (IS) due to cervical and cerebral artery dissection (CAD) is a rare entity, and few data are available on the use of such reperfusion therapies as intravenous fibrinolysis and mechanical thrombectomy in these patients. We analysed the use of these treatments in patients with IS due to CAD and compared them against patients receiving reperfusion treatment for IS of other aetiologies. METHOD: We conducted an observational, retrospective, multicentre study of patients with IS due to CAD recorded in the National Stroke Registry of the Spanish Society of Neurology during the period 2011-2019. Comparative analyses were performed between: a) patients with CAD treated and not treated with reperfusion therapies and b) patients treated with reperfusion for IS due to CAD and patients treated with reperfusion for IS due to other causes. Epidemiological data, stroke variables, and outcomes at discharge and at 3 months were included in the analysis. RESULTS: The study included 21,037 patients with IS: 223 (1%) had IS due to CAD, of whom 68 (30%) received reperfusion treatment. Reperfusion treatments were used less frequently in cases of vertebral artery dissection and more frequently in patients with carotid artery occlusion. Compared to patients with IS due to other causes, patients with CAD were younger, more frequently underwent mechanical thrombectomy, and less frequently received intravenous fibrinolysis. Rates of haemorrhagic complications, mortality, and independence at 3 months were similar in both groups. CONCLUSIONS: Reperfusion therapy is frequently used in patients with IS due to CAD. The outcomes of these patients demonstrate the efficacy and safety of reperfusion treatments, and are comparable to the outcomes of patients with IS due to other aetiologies.

Adenylyl cyclase amino acid sequence: possible channel- or transporter-like structure.

Complementary DNA's that encode an adenylyl cyclase were isolated from a bovine brain library. Most of the deduced amino acid sequence of 1134 residues is divisible into two alternating sets of hydrophobic and hydrophilic domains. Each of the two large hydrophobic domains appears to contain six transmembrane spans. Each of the two large hydrophilic domains contains a sequence that is homologous to a single cytoplasmic domain of several guanylyl cyclases; these sequences may represent nucleotide binding sites. An unexpected topographical resemblance between adenylyl cyclase and various plasma membrane channels and transporters was observed. This structural complexity suggests possible, unappreciated functions for this important enzyme.

B-cell translocation gene 2 is over-expressed in peri-infarct neurons after ischaemic stroke.

OBJECTIVES: Recovery from stroke is dependent on the survival of neurons in the dynamic peri-infarcted region. Although several markers of neuronal injury and apoptotic cell death have been described, administration of neuroprotective drugs directed at specific molecules has had limited success. A complete understanding of deregulated genes associated with neuronal death would be beneficial. Our previous microarray studies identified increased expression of a novel protein, the B-cell translocation gene 2 (BTG2), in infarcted regions. METHODS: We have used immunohistochemistry and Western blotting to examine the expression and localization of BTG2 in stroked brain tissue and immunofluorescent staining of human fetal brain neurons to determine if oxygen-glucose deprivation affected its expression. RESULTS: We show that BTG2 is strongly expressed in peri-infarcted and infarcted regions of brain tissue, localizing in neuronal nuclei and cytoplasm, whilst being absent or very weakly expressed in normal looking contralateral tissue. Exposure of human fetal brain neurons to oxygen-glucose deprivation also induced BTG2 expression in the cytoplasm and perinuclear regions of cells staining positive for propidium iodide (a marker of nuclear damage). CONCLUSIONS: BTG2 may be a modulator of cell survival and differentiation and could help to protect against cell death by inhibition of necrosis and/or apoptotic signalling pathways.

Simvastatin in the acute phase of ischemic stroke: a safety and efficacy pilot trial.

Although statins are being used for secondary prevention of ischemic stroke, recent experimental data have shown new pleiotropic effects of these drugs responsible for their role in neuroprotection. We conducted a pilot, double-blind, randomized, multicenter clinical trial to study for the first time safety and efficacy of simvastatin in the acute phase of ischemic stroke. Simvastatin/placebo was given at 3-12 h from symptom onset to 60 patients with cortical strokes. Efficacy on the evolution of several inflammation markers [interleukin (IL)-6, IL-8, IL-10, monocyte chemoattractant protein-1, intercellular adhesion molecule-1, vascular cell adhesion molecule-1, C-reactive protein, sApo/Fas, tumor necrosis factor-alpha, E-selectin, L-selectin and nitrites+nitrates] and neurological outcome was evaluated at baseline, day 1, 3, 5, 7 and 90. No differences were found amongst the biomarkers studied regarding treatment allocation. Although simvastatin patients improved significantly by the third day (46.4% vs. 17.9%, P = 0.022), a non-significant increase in mortality and greater proportion of infections (odds ratio 2.4, confidence interval 1.06-5.4) in the simvastatin group were the main safety concerns. Therefore, a larger clinical trial is needed to confirm the net benefit of this therapeutic approach.

Leukaemia inhibitory factor is over-expressed by ischaemic brain tissue concomitant with reduced plasma expression following acute stroke.

Leukaemia inhibitory factor (LIF) is a glycoprotein of the interleukin-6 family, which has potent pro-inflammatory properties and is involved in regulation of neuronal differentiation. We have previously identified its upregulation in gene microarrays following acute ischaemic stroke in man. LIF expression and localization was measured in human ischaemic stroke autopsy specimens, in a rat model of middle cerebral artery occlusion (MCAO) and in human foetal neural cell cultures following oxygen-glucose deprivation (OGD) by Western blotting and immunohistochemistry. Circulating LIF was determined in the plasma of patients in the hyper-acute stroke phase using a multiplex enzyme-linked-immunosorbent serologic assay system. Patients demonstrated an increase in LIF expression in peri-infarcted regions with localization in neurons and endothelial cells of microvessels surrounding the infarcted core. The rat MCAO model showed similar upregulation in neurons with a peak increase at 90 min. Circulating serum LIF expression was significantly decreased in the hyper-acute phase of stroke. Brain-derived neurons and glia cultured in vitro demonstrated an increase in gene/protein and protein expression respectively following exposure to OGD. Increased LIF expression in peri-infarcted regions and sequestration from the peripheral circulation in acute stroke patients are characteristic of the pathobiological response to ischaemia and tissue damage.

Atherothrombosis and plaque heterology: different location or a unique disease?

Formation of unstable plaques frequently results in atherothrombosis, the major cause for ischaemic stroke, myocardial infarction and peripheral arterial disease. Patients who have symptomatic thrombosis in one vascular bed are at increased risk of disease in other beds. However, the development of the disease in carotid, coronary and peripheral arteries may have different pathophysiology suggesting that more complex treatment protocols may have to be designed to reduce plaque development at different locations. In this review we describe the known risk factors, compare the developmental features of coronary and carotid plaque development and determine their association with end-point ischaemic events. Differences are also seen in the genetic contribution to plaque development as well as in the deregulation of gene and protein expression and cellular signal transduction activity of active cells in regions susceptible to thrombosis. Differences between carotid and coronary artery plaque development might help to explain the differences in anatomopathological appearance and risk of rupture.

Monomeric C-reactive protein--a key molecule driving development of Alzheimer's disease associated with brain ischaemia?

Alzheimer's disease (AD) increases dramatically in patients with ischaemic stroke. Monomeric C-reactive protein (mCRP) appears in the ECM of ischaemic tissue after stroke, associating with microvasculature, neurons and AD-plaques, Aß, also, being able to dissociate native-CRP into inflammatory, mCRP in vivo. Here, mCRP injected into the hippocampal region of mice was retained within the retrosplenial tract of the dorsal 3rd ventrical and surrounding major vessels. Mice developed behavioural/cognitive deficits within 1 month, concomitant with mCRP staining within abnormal looking neurons expressing p-tau and in beta-amyloid 1-42-plaque positive regions. mCRP co-localised with CD105 in microvessels suggesting angiogenesis. Phospho-arrays/Western blotting identified signalling activation in endothelial cells and neurons through p-IRS-1, p-Tau and p-ERK1/2-which was blocked following pre-incubation with mCRP-antibody. mCRP increased vascular monolayer permeability and gap junctions, increased NCAM expression and produced haemorrhagic angiogenesis in mouse matrigel implants. mCRP induced tau244-372 aggregation and assembly in vitro. IHC study of human AD/stroke patients revealed co-localization of mCRP with Aß plaques, tau-like fibrils and IRS-1/P-Tau positive neurons and high mCRP-levels spreading from infarcted core regions matched reduced expression of Aß/Tau. mCRP may be responsible for promoting dementia after ischaemia and mCRP clearance could inform therapeutic avenues to reduce the risk of future dementia.

CDP-choline reduces pro-caspase and cleaved caspase-3 expression, nuclear DNA fragmentation, and specific PARP-cleaved products of caspase activation following middle cerebral artery occlusion in the rat.

Citicoline has been demonstrated to be beneficial in several models of cerebral ischaemia. We tested the hypothesis that citicoline may provide apoptotic pathways following focal cerebral ischaemia. Focal cerebral ischaemia was produced by distal, permanent middle cerebral artery occlusion (MCAO) in Sprague-Dawley rats. The animals were randomised into four groups: (B+A) Citicoline 500 mg/kg IP 24 and 1 h before MCAO, and 23 h after MCAO; (A) citicoline 500 mg/kg IP, within 30 min after MCAO, and 23 h after MCAO; (C) vehicle IP; and (D) sham-operated. The animals were sacrificed at 12 h (n=8 per group) and 24 h (n=8 per group) after MCAO. Immunohistochemistry was performed on free-floating tissue sections with goat polyclonal antibodies to procaspase-1, -2, -3, -6 and -8, and in paraffin-embedded sections processed for cleaved caspase-3 (17 kDa) immunohistochemistry. Finally, some sections were stained with the method of in situ end-labelling of nuclear DNA fragmentation. For gel electrophoresis and Western blotting, antibodies to poly (ADP-ribose) polymerase (PARP) products of 89 kDa were used to reveal specific cleavage substrates of caspases. MCAO induced the expression of all procaspases and the expression of PARP products of 89 kDa, as well as cells with nuclear DNA fragmentation, at 12 and 24 h, in the infarcted core and penumbra. Citicoline reduced the expression of all procaspases at 12 and 24 h after MCAO, as well as the expression of cleaved caspase-3 in cells in the penumbra area. This was accompanied by a reduction in the number of cells bearing nuclear DNA fragments. The expression of caspase-cleaved products of PARP (PARP 89 kDa) was reduced in citicoline-treated ischaemic rats. These results show that citicoline inhibits the expression of proteins involved in apoptosis following MCAO.

Optimization of substituted N-3-benzylimidazoquinazolinone sulfonamides as potent and selective PDE5 inhibitors.

A previous report from these laboratories identified the N-3-benzylimidazoquinazolinone nucleus as a more selective PDE5 inhibitor template compared to the pyrazolopyrimidine of sildenafil. This paper describes in detail the structure-activity relationships of a set of sulfonamide analogues, several of which are both more potent and more selective PDE5 inhibitors in vitro than sildenafil. The synthesis, in vitro enzyme activity and selectivity, and in vitro functional and preclinical pharmacokinetic assessment of molecules in this series are described.

N-3-substituted imidazoquinazolinones: potent and selective PDE5 inhibitors as potential agents for treatment of erectile dysfunction.

Phosphodiesterase type 5 (PDE5) inhibitors with improved PDE isozyme selectivity relative to sildenafil may result in agents for the treatment of male erectile dysfunction (MED) with a lower incidence of PDE-associated adverse effects. This paper describes the discovery of 14, a PDE5 inhibitor with improved potency and selectivity in vitro compared to sildenafil. This compound shows activity in a functional assay of erectile function comparable to that of sildenafil.

Genetic resistance to gastrointestinal nematode parasites in Polish long-wool sheep.

A study was undertaken from 1991 to 1994 on a farm in southern Poland to evaluate the genetic parameters of resistance to gastrointestinal nematodes. The predominant species were Teladorsagia circumcincta and Haemonchus contortus. A total of 32 sires were evaluated, around 15 per year. Faecal egg counts were measured twice during the 4-month grazing season for lambs (total 659 lambs) and three times for their mothers (total 327 ewes). Infection levels were high during the first 2 years and low during the last 2 years. Using an animal model, the heritability of log10(epg+25) increased from 0.20 in August to 0.33 in September for lambs, and from 0.18 in May to 0.25 in September for ewes. The repeatability of ewe faecal egg count between years was 0.25. A genetic correlation of 0.58 was found between faecal egg count in ewes and in 6-7-month-old lambs. A negative genetic correlation (-0.61) was estimated between faecal egg count in September and daily weight gain of lambs from 70 days of age to the end of grazing season (7 months of age). The results confirm the feasibility of genetic selection of sheep for resistance to nematode parasites in an environment where T. circumcincta and H. contortus are the dominant species.

Activation of MAP kinase (ERK-1/ERK-2), tyrosine kinase and VEGF in the human brain following acute ischaemic stroke.

We examined expression of vascular endothelial growth factor (VEGF), phosphorylation of mitogen activated protein kinase (MAP) kinase (ERK1 and ERK2) and tyrosine phosphorylation in 19 patients (aged 58-90 years; mean 75) who died 1-44 days after acute ischaemic stroke. In the grey matter penumbra, 13 of 19 patients showed an increase in MAP kinase tyrosine phosphorylation (ERK1; 2.0- to 8-fold, ERK2; 2.2- to 11-fold) compared with normal contralateral tissue. In almost all cases, ERK-2 phosphorylation was higher than ERK1. Of these 13 patients, 11 also showed a general increase in tyrosine kinase phosphorylation, and eight expressed increased levels of VEGF protein (2.5- to 5-fold). In tissue examined directly from the infarct core, activation of the above proteins was not observed in the, majority of patients. In the white matter, seven of 19 patients (penumbra), and nine of 19 patients (stroke) had an increase in MAP kinase tyrosine phosphorylation (ERK1; 2.0- to 4.6-fold and ERK-2; 2.3- to 5.4-fold respectively) compared with normal contralateral tissue. There was no relationship between activation of MAP kinase and expression of VEGF. Examination of phosphorylated MAP kinase by immunohistochemistry revealed an increase in immunoreactivity in neurones, astroglial cells, reactive microglia and endothelial cells in areas surrounding infarcts, especially in areas with the highest density of microvessels. In conclusion, chronic activation of tyrosine phosphorylated events, in particular redistribution and phosphorylation of MAP kinase (ERK1/ERK2) occurs consistently in the grey matter penumbra of brain tissue following ischaemic stroke, and may be associated with increase in expression of VEGF. These signal transduction events could be important determinants of the extent of neuronal survival and/or angiogenic activity in the recovering brain tissue.

Acoustic analysis of dysarthria profile in ALS patients.

Dysarthria is a leading disability in ALS patients with motor neurone degeneration in the bulbar region. Although different approaches have been tried in the past, currently, no test is available to detect and follow the progression of dysarthria. We studied 53 patients with definite (n=27) or probable (n=26) ALS (the bulbar onset group n=15, the limb onset group n=38, mean age 53. 66/29-76 years/) according to El Escorial criteria. Each patient was seen by a neurologist every 10-12 weeks and clinical performance was assessed using the Norris scale. To evaluate dysarthria we developed a computer-based acoustic method. All patients had computer-analysed speech sound tests done three times. The most significantly affected vowels were selected for further studies. A method based on the Euclidian principle was used and the results were compared with 30 age, sex-matched, healthy control subjects. Our results demonstrated the existence of a specific dysarthria profile in ALS patients with most significantly affected vowels: 'B', 'O', 'I', 'W', 'T' in the bulbar group, and: 'B', 'I', 'T', 'W', 'O' in the limb group. This study suggests that it is possible to detect and monitor the progression of the disease based on the acoustic analysis of only several sounds. Abnormalities detected in the dysarthria profile may appear prior to any clinical symptoms of the disease.

Changing patterns of migration to Australia and their influence on the health of migrants.

Whilst before World War II migration to Australia was almost entirely from the British Isles, over 60% of post-War II migrants came from other countries other than Britain. They arrived in Australia in distinct waves: Eastern European refugees were followed by migrants from Western Europe, who were later replaced by migrants from the Mediterranean Basin and finally by Asians, initially from the Indian subcontinent, afterwards from Lebanon and most recently from Indo-China. These patterns of migration were changing the numerical size, age distribution and length of residence in Australia of the different ethnic groups. The paper describes the influence of these changes on physical and mental health of the migrants. Physical morbidity was related to 'imported diseases', to the different physical and social environment and to differences and changes in eating and other habits. Psychiatric disorders were associated with traumatic experiences encountered prior to migration, and with stresses of migration and adjustment to the new country. Thus, in evaluating the health of immigrants, one has to take into account the sources from which the migrants were drawn, their situation in the host society, their numerical growth and age distribution, as well as acculturation to the country settlement.

Soluble intercelluar adhesion molecule-1, E-selectin, vascular cell adhesion molecule-1 and von Willebrand factor in stroke.

We investigated the role of endothelial cell and leukocyte adhesion in the pathophysiology of acute stroke. The immunocytochemical expression of adhesion molecules in brain tissue from six patients who died following acute ischaemic stroke showed weak endothelial expression of intercellular adhesion molecule-1 (ICAM-1), but intense expression of vascular cell adhesion molecule-1 (VCAM-1) by astrocytes and endothelial cells from the infarcted, but not the non-infarcted areas. We also measured soluble adhesion molecules E-selectin, ICAM-1, VCAM-1 and von Willebrand factor (all by enzyme-linked immunosorbent assay) in 21 patients after an acute ischaemic stroke (ictus < 12 h), and again 3 months later. Blood levels in the stroke patients were compared with 82 healthy controls and 22 subjects with carotid atherosclerosis. Compared with healthy controls, both patient groups had raised levels of von Willebrand factor (P < 0.02) but the level of soluble VCAM-1 was raised only in patients with acute stroke (P < 0.02). Levels of von Willebrand factor and soluble VCAM-1 in the stroke patients were still high at 3 months follow-up. We suggest that there might be changes in adhesion molecule expression and release in the acute and chronic stages of ischaemic stroke, where blood levels are related to immunocytochemical findings on infarcted brain. These changes may perhaps be part of the complex pathophysiological responses to infarction and repair of brain tissue following stroke.