Grupo de Estudio de Enfermedades Cerebrovasculares de la SEN

Minimizing acquisition time of arterial spin labeling at 3T.

Magn Reson Med. 2008 Jun;59(6):1467-71

Authors: Fernández-Seara MA, Edlow BL, Hoang A, Wang J, Feinberg DA, Detre JA

An improved arterial spin labeling (ASL) perfusion technique that combines pseudo-continuous labeling and a T2*-insensitive sequence (GRASE) with background suppression was used to acquire perfusion maps in normal volunteers and stroke patients. It is shown that perfusion measurements obtained in less than 1 min of scan time are reproducible, with a coefficient of variation of 7%. The perfusion maps generated from these data can be used to characterize the stroke lesion.

PMID: 18506806 [PubMed - indexed for MEDLINE]

SEPS1 gene is activated during astrocyte ischemia and shows prominent antiapoptotic effects.

J Mol Neurosci. 2008 Jul;35(3):259-65

Authors: Fradejas N, Pastor MD, Mora-Lee S, Tranque P, Calvo S

Contrarily to neurons, astrocytes can survive short periods of ischemia. We have searched for genes implicated in astrocyte resistance to ischemia using oxygen and glucose deprivation (OGD) as a stroke model. A RNA differential display approach uncovered the OGD induction of selenoprotein-S-encoding gene SEPS1. This endoplasmic reticulum (ER) resident protein is known to promote cell survival regulating the ER stress as well as inflammation. We found that suppression of SEPS1 by small interfering RNA severely increases astrocyte injure caused by OGD, suggesting that selenoprotein S protects astrocytes against ischemia. Our data also support that modulation of ER stress is implicated in this effect.

PMID: 18498015 [PubMed - indexed for MEDLINE]

Outcome of bilateral deep brain subthalamic stimulation in patients carrying the R1441G mutation in the LRRK2 dardarin gene.

Neurosurgery. 2008 Apr;62(4):857-62; discussion 862-3

Authors: Gómez-Esteban JC, Lezcano E, Zarranz JJ, González C, Bilbao G, Lambarri I, Rodríguez O, Garibi J

OBJECTIVE: Deep brain subthalamic stimulation provides symptomatic relief to patients with Parkinson's disease. The present study analyzes the postoperative outcome of deep brain subthalamic stimulation in patients carrying the R1441G mutation in the leucine-rich repeat kinase-2 (LRRK2) (dardarin) gene. METHODS: Five of the 48 patients treated in our unit carried a mutation in the LRRK2 (dardarin) gene. All five met the Core Assessment Program for Surgical Interventional Therapies criteria for inclusion in the surgical program. Pre- and postoperative assessment (6 mo) was made using the Unified Parkinson Disease Rating Scale II, Unified Parkinson Disease Rating Scale III, and Parkinson's Disease Questionnaire-39 scores, as well as the type and dosage of drugs used. RESULTS: The response to L-dopa after 6 months was similar to the baseline in all four patients. One suffered a stroke four months after surgery and is not eligible for evaluation. The improvements in motor response, daily life activities, and quality of life were limited (18, 22, and 33%, respectively) and were lower than those of the control group (39, 45, and 41%, respectively). DISCUSSION: Carriers of the R1441G mutation were clinically analogous to the rest of similarly operated patients with idiopathic Parkinson's disease. However, the response to deep brain subthalamic stimulation was worse among the former. The explanation for this negative result is unclear because all patients maintained an excellent response to L-dopa. Further larger studies are needed to confirm these findings.

PMID: 18496192 [PubMed - indexed for MEDLINE]

Quantification of left ventricular function and mass in heart transplant recipients using dual-source CT and MRI: initial clinical experience.

Eur Radiol. 2008 Sep;18(9):1784-90

Authors: Bastarrika G, Arraiza M, De Cecco CN, Mastrobuoni S, Ubilla M, Rábago G

The purpose of this study was to compare LV function and mass quantification derived from cardiac dual-source CT (DSCT) exams with those obtained by MRI in heart transplant recipients. Twelve heart transplant recipients who underwent cardiac DSCT and MRI examination were included. Double-oblique short-axis 8-mm slice thickness images were evaluated. Left ventricular ejection fraction, end-diastolic volume, end-systolic volume, stroke volume, cardiac output and myocardial mass were manually assessed for each patient by two blinded readers. A systematic overestimation of all left ventricular volumes by DSCT when compared with MRI was observed. Mean difference was 16.58 +/- 18.61 ml for EDV, 4.9 4 +/- 6.84 ml for ESV, 11.64 +/- 13.58 ml for SV and 5.73 +/- 1.14 l/min for CO. Slightly lower values for left ventricular ejection fraction with DSCT compared with MRI were observed (mean difference 0.34 +/- 3.18%, p = 0.754). Correlation between DSCT and MRI for left ventricular mass was excellent (rho = 0.972). Bland and Altman plots and CCC indicated good agreement between DSCT and MRI left ventricular function and mass measurements. The interobserver correlation was good. In conclusion, DSCT accurately estimates left ventricular ejection fraction, volumes and mass in heart transplant recipients.

PMID: 18491100 [PubMed - indexed for MEDLINE]

Complete atrioventricular block induced by rituximab in monotherapy in an aged patient with non-Hodgkin's diffuse large B-cell lymphoma.

Clin Transl Oncol. 2008 May;10(5):298-9

Authors: Cervera Grau JM, Esquerdo Galiana G, Belso Candela A, Llorca Ferrándiz C, Juárez Marroquí A, Maciá Escalante S

Rituximab is a treatment option to non-Hodg kin's diffuse large B-cell lymphoma (NHDLBCL) in advanced stage and comorbility. It is known the cardiotoxicity effect of this drug, but there is no previous report describing a complete atrioventricular block (CAVB) secundary to treatment with Rituximab. We present an elderly woman treated with monotherapy with Rituximab who experienced a CAVB after administration of the fifth dose of this drug.

PMID: 18490248 [PubMed - indexed for MEDLINE]

Fibrinolysis: the key to new pathogenetic mechanisms.

Curr Med Chem. 2008;15(9):923-9

Authors: Zorio E, Gilabert-Estellés J, España F, Ramón LA, Cosín R, Estellés A

The fibrinolytic system includes a broad spectrum of proteolytic enzymes with physiological and pathophysiological functions in several processes, such as haemostatic balance, tissue remodeling, tumor invasion, angiogenesis and reproduction. The main enzyme of the plasminogen activator system is plasmin, which is responsible for the degradation of fibrin into soluble degradation products. The activation of plasminogen into plasmin is mediated by two types of activators, urokinase-type plasminogen activator (uPA) and tissue-type plasminogen activator (tPA). The activity of both is regulated by specific plasminogen activator inhibitors (PAIs). There are 3 types of PAIs described so far but the most important fibrinolytic inhibitor in vivo is PAI type 1 (PAI-1). Among others, the presence of metabolic syndrome and the -675 4G/5G promoter polymorphism are known to be modulators of PAI-1 levels. Besides their fibrinolytic profile, plasmin and plasminogen activators are implicated in tissue proliferation and cellular adhesion, as they can proteolytically degrade the extracellular matrix and regulate the activation of both growth factors and matrix metalloproteinases. By all these means, the fibrinolytic system is also involved in physiological processes, and in pathological situations such as thrombosis, arteriosclerosis, endometriosis and cancer. PAI 1 has been studied in different settings with thrombotic pathophysiology, such as coronary artery disease and ischaemic stroke. Controversial results have been published and concerns about study designs or presence of confounders have been claimed to be responsible of them. Recently, its involvement in adverse thrombotic events related to the modern drug-eluting coronary stents has renewed the interest of its study. PAI-1 also plays an important role in signal transduction, cell adherence, and migration. Indeed, studies of several types of cancers, including breast cancer, have shown that increased uPA and PAI-1 levels are associated with aggressive tumor behavior and poor prognosis. Endometriosis is defined by the presence of endometrial glands and stroma outside the uterus with marked ability to attach and invade the peritoneum. It is one of the most frequent benign gynecological diseases that affect women with pelvic pain or infertility during their reproductive age. Immune system disorders, genetic predisposition, altered peritoneal environment and endometrial alterations are believed to increase the susceptibility to endometriosis. The plasminogen activator system may be involved in this process, where local extracellular proteolysis plays a crucial role. Altered expression of several components of the fibrinolytic system in both eutopic and ectopic endometrium and peritoneal fluid of women with the disease has been implicated not only in the onset, but also in the progression of the endometriotic lesions.

PMID: 18473800 [PubMed - indexed for MEDLINE]

Partial trisomy 13q22-qter associated to leukoencephalopathy and late onset generalised epilepsy.

Int Arch Med. 2008;1(1):5

Authors: Ribacoba R, Menendez-Gonzalez M, Hernando I, Salas J, Giros ML

ABSTRACT: The partial trisomy 13q.22 is an uncommon chromosomopathy. We present a case with a partial trisomic component 13q22 and a monosomic component 5p15 from paternal origin. This patient developed early menopause and major neurological disorders as leukoencephalopathy, late onset generalised epilepsy and stroke. She also had fatty acids disturbances and their potential relation to the neurological disorders and early menopause is discussed. The presented case illustrates the phenotype of 13q22-qter in adult age and reaffirms the importance of studying the karyotype of any patient with seizures or leukoencephalopathy particularly when there are associated other clinical features including stroke at a young age, fatty acids disturbances, microcephaly, hypotelorism, short neck, hemangiomata, short fingers or distal swell in thumbs.

PMID: 18471271 [PubMed - in process]

Clinical study of lacunar infarcts in non-hypertensive patients.

J Stroke Cerebrovasc Dis. 2003 Sep-Oct;12(5):232-6

Authors: Arboix A, Altés E, García-Eroles L, Massons J

Lacunar infarcts in non-hypertensive patients have been scantly assessed. The objective of this study was to determine clinical features of lacunar infarct in patients without hypertension (n = 91) in comparison with characteristics of lacunar infarcts occurring in patients with hypertension (n = 283) collected from a prospective hospital-based stroke registry in which 2000 patients with acute stroke are included. Predictors of lacunar infarct in patients without hypertension were assessed by multiple logistic regression analysis. The group of non-hypertensive patients with lacunar infarction showed a significantly higher frequency of male gender, age 85 years or older, history of atrial fibrillation, chronic obstructive pulmonary disease and diabetes mellitus, and a significantly lower frequency of female gender and absence of limitation at hospital discharge than hypertensive patients with lacunar infarct. Differences between hypertensive and non-hypertensive patients in relation to frequency of the different lacunar syndromes were not observed. After multivariate analysis, age 85 years or older (odds ratio 3.13), diabetes (odds ratio 2.57), and male gender (odds ratio 1.99) seemed to be independent factors associated with lacunar infarct in patients without hypertension. Lacunar infarct in non-hypertensive patients showed some differential clinical features compared to the remaining lacunar infarctions because it occurred more frequently in male patients aged 85 years or older. In this group, diabetes was the most important modifiable risk factor. These results suggest an earlier effect of arteriopathy caused by hypertension favoring lacunar brain ischemia, whereas in non-hypertensive patients, arteriopathy responsible for small vessel disease would take a more prolonged time in causing lacunar infarction.

PMID: 17903933 [PubMed]

Plasma thrombin-activatable fibrinolytic inhibitor (TAFI) among healthy subjects and patients with vascular diseases: a validation study.

Pathophysiol Haemost Thromb. 2003 Sep-2004 Dec;33(5-6):382-6

Authors: Monasterio J, Bermúdez P, Quiroga D, Francisco E, Meneses B, Montaner J

Thrombin activable fibrinolysis inhibitor antigen levels (TAFI Ag ) exhibit a great inter-individual variability in healthy populations. Our aim is to determine whether variability is due to physiologic variations depending on genetic control or due to validation of the method,in order to allow a better interpretation of the results inpatients with vascular diseases. With this purpose, we performed a strategy validation of specific ELISA method, Zymutest TAFI Ag Hyphen Biomed, base don a commercial monoclonal antibody. After methodology validation we have recently determined plasma TAFI Ag levels in several groups of diseases such as septic patients, menopause and cerebrovascular diseases. TAFI was finally determined in acute ischemic stroke to know its relationship with stroke evolution and response to thrombolytic treatments.

PMID: 15692248 [PubMed - indexed for MEDLINE]

[Cardiovascular diseases. Evaluation of the objectives of the Health Plan for Catalonia for the year 2000]

Med Clin (Barc). 2003;121 Suppl 1:20-5

Authors: Tresserras R, Castell C, Pardell H

Background and objective: Cardiovascular diseases (CVD) constitute one of the main public health problems in western countries. Interventions applied to minimize impact of these conditions were considered priority when aims of Catalonian Health Plan for 2000 were designed. The purpose of this paper will be evaluate whether this objectives have been fulfilled.Subjects and methods: We have studied the CVD age standardized mortality rate between 1983 and 2000 in subjects younger than 65. We have also analized this rate for stroke and renal failure, including all ages. By means of the Health Exam, we have studied the percentage of treated and controlled hypertense people, the average cholesterolemia and the hypercholesterolemia prevalence in the population ages 18-74.Results: Cardiovascular mortality in younger than 65 years old that should have experimented a 15% reduction, has decreased 32.6%. In the other hand, stroke mortality has decrease further than best expectations (55.7% instead of 20%). Mortality for chronic renal failure has kept constant. However the predicted 5% mortality reduction has not been achieved. The increase of hypertensed treated (50%), and controlled (75%) the reduction of average cholesterolemia (< 220 mg/100 ml) and hypercholesterolemia prevalence are some of the objectives achieved.Conclusions: The results show that the targets related to CVD, arterial hypertension and hypercholesterolemia have been widely fulfilled.

PMID: 15274821 [PubMed - in process]

Does nitric oxide contribute to iron-dependent brain injury after experimental cerebral ischaemia?

J Physiol Biochem. 2003 Dec;59(4):249-54

Authors: Gámez A, Carbonell T, Rama R

Experimental and clinical data suggest that iron has a key role in cerebral ischaemia. We measure infarct volume and analyse the nitric oxide responses to brain injury in rat stroke model after increased oral iron intake. Permanent middle cerebral artery occlusion (MCAO) was performed in a group of 20 male Wistar rats, 10 of which were fed with a control diet and 10 of which were fed with iron-enriched diet containing 2.5% carbonyl iron for 9 weeks. L-arginine and nitric oxide metabolites were determined in blood samples before and at 2, 6, 8 and 48 h after MCAO. Infarct volume, thiobarbituric acid reaction substances (TBARS) and tissue iron were measured at 48 h. Infarct volume was 66% greater in the iron-fed rats than in the control group. Iron-fed animals showed significantly higher levels of TBARS. Liver iron stores (3500 +/- 199 vs 352 +/- 28 microg Fe/g, p<0.0001) but not brain iron stores (131 +/- 11 vs 139 +/- 8 microg Fe/g, p=0.617), were significantly higher in the iron-fed group. L-arginine levels were slightly lower in iron-fed rats and decreased significantly in both groups at 6 and 8 hours after MCAO. The levels of the stable end products of NOS (NOx = nitrite + nitrate) were significantly higher in iron-fed rats before MCAO (16.2 +/- 2.2 vs. 9.6 +/- 0.8 micromol x L(-1), p<0.05), with a further increase during the six first hours after MCAO in both groups. These results suggest that the iron overload that increases both superoxide and nitric oxide production leads to peroxynitrite formation, thus enhancing brain damage.

PMID: 15164943 [PubMed - indexed for MEDLINE]

Association between inflammation and hemostatic markers in atherothrombotic stroke.

Thromb Res. 2003;112(4):217-21

Authors: Reganon E, Vila V, Martínez-Sales V, Vaya A, Lago A, Alonso P, Aznar J

INTRODUCTION: It has been reported that the influence of fibrinogen on the incidence of ischemic events is related to inflammation processes and reflects an association with advance atherosclerosis. The aim of this study was to evaluate the association of thrombogenic and inflammatory profiles in patients who have suffered a stroke. MATERIALS AND METHODS: The study involved 17 patients with atherothrombotic stroke and 34 healthy subjects as control group. The patients were examined 48 h, 3 and 6 months after the stroke occurred. To determine the inflammatory and thrombogenic profiles, plasma levels of fibrinogen, total sialic acid (TSA), C-reactive protein (CRP), tissue factor (TF) and fibrin D-dimer (D-dimer) were measured. RESULTS: The study showed that at 48 h and 3 months the levels of fibrinogen, TF, D-dimer, TSA and CRP were significantly higher than control group. TF, D-dimer and TSA remains significantly elevated throughout the entire study period. TF and D-dimer decreased over time without reaching the normal values. The multiple regression analysis showed that, at 48 h, 68% of the variance of fibrinogen and 22% of the variance of TF could be explained by the influence of CRP. At 3 and 6 months, 78% of the variance of fibrinogen could be explained by the influence of TSA. CONCLUSIONS: The results suggest a relation among inflammation markers, fibrinogen and TF in the acute phase of stroke. As TF and D-dimer are still elevated at 6 months, an increased thrombogenicity for a longer period following the acute event is present.

PMID: 14987914 [PubMed - indexed for MEDLINE]

Angiotensin receptor blocker as adjunctive therapy for rhythm control in atrial fibrillation: results of the irbesartan-amiodarone trial.

Card Electrophysiol Rev. 2003 Sep;7(3):243-6

Authors: Madrid AH, Escobar C, Rebollo JM, Marín I, Bernal E, Nannini S, Limón L, Peng J, Moro C

Atrial fibrillation (AF) is a common arrhythmia associated with increased risk of stroke and mortality. The early appearance of electrical remodeling is followed by structural remodeling of the atrial tissue. Direct current cardioversion of persistent AF is the most effective treatment for the restoration of sinus rhythm, but it is hampered by a high percentage of recurrences. Recurrences may be the consequence of both electrical and structural remodeling. A study on the use of irbesartan to maintain sinus rhythm in patients with long-lasting persistent AF showed that this angiotensin II receptor blocker combined with amiodarone prolonged sinus rhythm after cardioversion. Irbesartan may have antifibrotic effects due not only to the ability to diminish the synthesis of collagen type I molecules but also to its capacity to stimulate the degradation of collagen type I fibers, as has been demonstrated with losartan, another angiotensin II receptor blocker. This suggests that efforts to reduce the structural changes that occur during AF may be more useful in preventing recurrences than efforts designed to minimize the electrical changes alone. The AFFIRM trial compared two approaches to the treatment of AF: cardioversion with antiarrhythmic drugs to maintain sinus rhythm and the use of rate-controlling drugs. The results show that management of AF with the rhythm-control strategy offers no survival advantage over the rate-control strategy. However, non-antiarrhythmic drugs to prevent recurrences, like irbesartan, were not controlled and amiodarone was used in a low percentage of the patients. The treatment strategies proposed in both AFFIRM and RACE, in our opinion, may not be the optimal. The modern clinical approach to AF involves an early intervention to restore sinus rhythm, therefore preventing atrial remodeling. The pretreatment of patients with AF who undergo electrical cardioversion is very important and will be the subject for continuous improvement.

PMID: 14739722 [PubMed - indexed for MEDLINE]

[Treatment of postmenopausal osteoporosis]

An Sist Sanit Navar. 2003;26 Suppl 3:91-8

Authors: Loza E

Prevention and treatment of osteoporosis consists of non-drug and drug therapy. This review of the topic will provide an overview of the approach to therapy of osteoporosis in postmenopausal women. In the past, estrogen replacement was considered a primary therapy for the prevention of postmenopausal osteoporosis. However, data from the Wome&#x144;s Health Initiative (WHI) revealed that estrogen-progestine therapy does not reduce the risk of coronary heart disease, and increases the risk of breast cancer, stroke, and venous thromboembolic events. As a result of these findings, other antiresorptive agents are now the drugs of choice for the prevention and treatment of osteoporosis in postmenopausal women.

PMID: 14716361 [PubMed - indexed for MEDLINE]

The release of tumor necrosis factor-alpha is associated with ischemic tolerance in human stroke.

Ann Neurol. 2003 Dec;54(6):811-9

Authors: Castillo J, Moro MA, Blanco M, Leira R, Serena J, Lizasoain I, Dávalos A

Tumor necrosis factor (TNF)-alpha overexpression has been related to experimental ischemic tolerance when transient ischemia precedes cerebral infarction. We investigated TNF-alpha and interleukin (IL)-6 plasma concentrations in 283 patients with an acute stroke within 24 hours after symptom onset. An ipsilateral transient ischemic attack (TIA) within 72 hours before stroke was recorded in 38 patients. The infarct volume measured on computed tomography on days 4 to 7 and the frequency of poor outcome (Barthel Index score < 85) at 3 months were significantly lower in patients with prior TIA. Plasma concentrations of TNF-alpha were higher (42.5 +/- 9.9 vs 13.1 +/- 6.4pg/ml, p < 0.0001) and IL-6 levels were lower (10.1 +/- 6.2 vs 28.3 +/- 17.3pg/ml, p < 0.0001) in patients with prior TIA. A new variable termed TNF-alpha/IL-6 index was considered positive when TNF-alpha was greater than 30pg/ml and IL-6 was less than 30pg/ml. Positive TNF-alpha/IL-6 index was found in 92% of patients with prior TIA and in 1% of those without. TNF-alpha/IL-6 index (p = 0.0003) and TIA (p = 0.0001) were associated with good outcome in logistic regression analysis after adjusting for potential confounding factors. Ischemic tolerance in acute stroke is associated with increased plasma levels of TNF-alpha in the presence of reduced concentrations of IL-6.

PMID: 14681891 [PubMed - indexed for MEDLINE]

Improving the predictive accuracy of recanalization on stroke outcome in patients treated with tissue plasminogen activator.

Stroke. 2004 Jan;35(1):151-6

Authors: Molina CA, Alexandrov AV, Demchuk AM, Saqqur M, Uchino K, Alvarez-Sabín J,

BACKGROUND AND PURPOSE: Although early recanalization is a powerful predictor of stroke outcome after thrombolysis, some stroke patients remain disabled despite tissue plasminogen activator (tPA)-induced recanalization. Therefore, we sought to investigate whether the predictive accuracy of early recanalization on stroke outcome is improved when combined with clinical and radiological information. METHODS: We evaluated 177 patients with nonlacunar strokes in the middle cerebral artery (MCA) treated with intravenous tPA who were followed up during 3 months. Transcranial Doppler monitoring of recanalization was conducted during the first hours after tPA administration. The relative contribution of clinical, transcranial Doppler, and radiological information on stroke outcome was evaluated. We used logistic regression to derive a predictive model for good outcome (modified Rankin Scale score < or =2) after thrombolysis. RESULTS: Median National Institutes of Health Stroke Scale (NIHSS) score before tPA was 16. At 3 months, 87 patients (49.2%) became functionally independent (modified Rankin Scale score < or =2). In a logistic regression model, degree of recanalization within 300 minutes (P<0.001), proximal MCA occlusion (P<0.001), baseline NIHSS score (P=0.0013), systolic blood pressure (P=0.0116), and early ischemic changes on CT (P=0.0253) independently predicted outcome at 3 months. A 5-item score was developed on the basis of the factors significantly associated with stroke outcome in the logistic regression (total score range, 0 to 7). The likelihood of good outcome at 3 months was 0.82 (95% CI, 0.72 to 0.92) in patients who scored 0 to 2, 0.51 (95% CI, 0.36 to 0.66) in those who scored 3 to 4, and 0.15 (95% CI, 0.05 to 0.25) in those who scored 5 to 7 points. CONCLUSIONS: The combination of clinical, radiological, and hemodynamic information predicts with a high accuracy long-term stroke outcome during or shortly after intravenous tPA administration.

PMID: 14671245 [PubMed - indexed for MEDLINE]

Neutrophil infiltration increases matrix metalloproteinase-9 in the ischemic brain after occlusion/reperfusion of the middle cerebral artery in rats.

J Cereb Blood Flow Metab. 2003 Dec;23(12):1430-40

Authors: Justicia C, Panés J, Solé S, Cervera A, Deulofeu R, Chamorro A, Planas AM

Matrix metalloproteinase-9 (MMP-9) activity increases in the brain during the first day after focal ischemia and might be involved in the pathogenesis of tissue damage. We previously showed MMP-9 in the extracellular space of brain parenchyma along with neutrophil recruitment after ischemia. In the present study, we tested whether neutrophils were a direct source of enhanced MMP-9 in the ischemic brain. Neutrophil infiltration was prevented either by injecting an antibody against ICAM-1, which abrogates neutrophil adhesion to the endothelial vessel wall, or by inducing neutropenia. One-hour intraluminal middle cerebral artery occlusion with reperfusion was induced, and studies were performed at 24 hours. Circulating neutrophils expressed 95-kDa MMP-9 and dimers, and infiltrated neutrophils stained positive for MMP-9. The expression of MMP-9 (mainly 95-kDa proform and dimers and, to a lesser extent, 88-kDa form) increased in brain after ischemia/reperfusion. Treatments preventing neutrophil infiltration failed to preclude the ischemia-induced increase in 88-kDa MMP-9 form and gelatinase activity in neurons and blood vessels. However, these treatments prevented the major increase in 95-kDa MMP-9 form and dimers. We conclude that neutrophil infiltration highly contributes to enhanced MMP-9 in the ischemic brain by releasing MMP-9 proform, which might participate in the tissular inflammatory reaction.

PMID: 14663338 [PubMed - indexed for MEDLINE]

Plasmatic level of neuroinflammatory markers predict the extent of diffusion-weighted image lesions in hyperacute stroke.

J Cereb Blood Flow Metab. 2003 Dec;23(12):1403-7

Authors: Montaner J, Rovira A, Molina CA, Arenillas JF, Ribó M, Chacón P, Monasterio J, Alvarez-Sabín J

Sixteen patients with acute middle cerebral artery stroke were studied to correlate neuroinflammatory markers with perfusion- and diffusion-weighted magnetic resonance imaging (MRI) lesion volumes (PWI and DWI). At arrival (less than 6 hours), plasmatic matrix metalloproteinase (MMP)-9, MMP-2, interleukin (IL)-6, IL-8, intercellular adhesion molecule (ICAM)-1, and tumor necrosis factor (TNF)-alpha were serially measured (by ELISA), and MRI was performed. In cerebral ischemia, tissue destruction seems related to matrix metalloproteinases expression because baseline MMP-9 was the only predictor of the infarct volume measured as a DWI lesion (lineal regression: b = 0.50, 0.25-0.74; P < 0.001). Moreover, the extent of hypoperfused brain area (PWI) was associated with a proinflammatory cytokine release in the next hours (TNF-alpha and IL-6).

PMID: 14663335 [PubMed - indexed for MEDLINE]

Pharmacological profile of phytoestrogens in cerebral vessels: in vitro study with rabbit basilar artery.

Eur J Pharmacol. 2003 Dec 15;482(1-3):227-34

Authors: Torregrosa G, Burguete MC, Pérez-Asensio FJ, Salom JB, Gil JV, Alborch E

As a previous step to consider their use in the pharmacology for stroke, we investigated the effects of four phytoestrogens (i.e. genistein, daidzein, zearalanone and biochanin A) on cerebral vessels. Cerebral vascular responses were analyzed by conventional recording of isometric tension in rabbit basilar artery segments kept in organ bath under standard conditions. The four phytoestrogens elicited concentration-dependent relaxant responses of different potency in basilar artery segments previously contracted with either 5x10(-2) M KCl or 10(-4) M UTP. Neither endothelium removal, 10(-4) M N(omega)-nitro-L-arginine methyl ester (L-NAME, nitric oxide (NO) synthase inhibitor), 10(-5) M1 H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ, selective inhibitor of NO-sensitive guanylyl cyclase), 10(-5) M 4H-8-bromo-1,2,4-oxadiazolo(3,4-d)benz(b)(1,4)oxazin-1-one (NS2028, specific soluble guanylyl cyclase inhibitor), nor 10(-5) M indomethacin (prostaglandin biosynthesis inhibitor) modified the phytoestrogen-elicited vasorelaxant responses. On the other hand, Ca(2+)-elicited contractile responses were effectively inhibited in the presence of phytoestrogens. Phytoestrogens act as cerebrovascular relaxants by a mechanism which involves Ca(2+) entry blockade in the vascular smooth muscle rather than stimulation of vasorelaxant endothelium-related mechanisms such as NO/cGMP or prostaglandins.

PMID: 14660027 [PubMed - indexed for MEDLINE]

[Eales' disease with bilateral brain strokes and jaw-closing dystonia]

Neurologia. 2003 Dec;18(10):750-3

Authors: Jiménez PE, Marsal C, Velázquez JM, Alvarez A

Eales' disease is an idiopathic occlusive vasculopathy of the retina, which is characterized by extensive peripheral non-perfusion, perivascular sheathing, and neovascularization. It is associated with recurrent vitreous hemorrhages. Both eyes are affected consecutively in 80% to 90% of the patients. In spite of the multiple theories that have been proposed, it continues to have unknown origin and its diagnosis relies on exclusion of other causes of retinal vasculopathy. In some occasions, these patients develop complications of the central nervous system, above all brain infarcts. We present the case of a 38 year old woman with Eales' disease who developed bilateral brain infarcts associated with occlusion or stenosis of the middle cerebral arteries. The cerebral angiography showed beading of the Silvian arteries, suggestive of an underlying inflammatory disorder. Early corticosteroid therapy could avoid contralateral retinal involvement and neurological complications. The patient also presented delayed jaw closing dystonia secondary to basal ganglia infarct which followed a benign course with spontaneous resolution in a few days.

PMID: 14648353 [PubMed - indexed for MEDLINE]