Abstracts of Literature.

Abstract

HomeStrokeVol. 30, No. 10Abstracts of Literature Free AccessOtherPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessOtherPDF/EPUBAbstracts of Literature Askiel Bruno and Engin Y. Yilmaz Askiel BrunoAskiel Bruno Search for more papers by this author and Engin Y. YilmazEngin Y. Yilmaz Search for more papers by this author Originally published1 Oct 1999https://doi.org/10.1161/01.STR.30.10.2249Stroke. 1999;30:2249–2255Cerebral AneurysmsAB-14482-99 Surgical and Endovascular Treatment of Unruptured Cerebral Aneurysms at University Hospitals—Johnston SC (Dept of Neurology, Box 0114, Univ of California, San Francisco, 505 Parnassus Ave, San Francisco, CA 94143-0114), Dudley RA, Gress DR, Ono L—Neurology. 1999;52:1799–1805. Copyright ©1999 by the American Academy of Neurology.Objective: To compare complications of surgical clipping and coil embolization in the treatment of unruptured aneurysms. Background: Surgical clipping has been the preferred treatment for unruptured cerebral aneurysms but endovascular coil embolization is an increasingly employed alternative. No direct comparisons of the techniques are available to guide clinical decision making. Methods: We performed a cohort study of patients treated for unruptured cerebral aneurysms at 60 university hospitals from January 1994 through June 1997 using the University HealthSystem Consortium database. The database was validated by chart review from one of the participant universities. The main outcome measures were in-hospital mortality and adverse outcomes, defined as in-hospital deaths and discharges to nursing homes or rehabilitation hospitals. Results: The primary treatment modality was surgical in 2,357 cases and endovascular in 255 cases. Adverse outcomes were significantly more common in surgical cases (18.5%) compared to endovascular cases (10.6%) (p=0.002), and the difference was not altered after adjusting for age, sex, race, transfer admissions, emergency room admissions, and year of treatment (odds ratio [OR] 2.1, 95% confidence interval [CI] 1.4 to 3.3; p=0.001). In-hospital mortality was also increased in surgical cases (2.3% versus 0.4%; p=0.039), but the difference was not significant in the multivariable model (OR 6.3, 95% CI 0.9 to 46.1; p=0.07). Length of stay and hospital charges were significantly greater for surgical cases (p<0.0001 for each), and these differences were not affected by risk adjustment. Conclusion: Endovascular coil embolization resulted in fewer adverse outcomes than surgery for unruptured cerebral aneurysms treated at the university hospitals studied. Although these results should be seen as preliminary, the magnitude of difference and current predominance of surgery appear to justify a randomized trial.Key Words: cerebral aneurysm, endovascular therapyAB-14483-99Role of Transcranial Doppler Monitoring in the Diagnosis of Cerebral Vasospasm After Subarachnoid Hemorrhage—Vora YY, Suarez-Almazor M, Steinke DE, Martin ML, Findlay JM (2D3.77 WMC, Univ of Alberta Hospital, 8440 112th St, Edmonton, Alberta T6G 2B7, Canada)—Neurosurgery. 1999;44:1237–1248.OBJECTIVE: The purpose of this study was to determine the correlation between transcranial Doppler (TCD) velocities and angiographic vasospasm after aneurysmal subarachnoid hemorrhage.METHODS: In the first part of this study, patients were retrospectively reviewed to correlate middle cerebral artery absolute blood flow velocities with angiographic vasospasm. In the second part of the study, the middle cerebral artery/ipsilateral extracranial internal carotid artery velocity ratio (Lindegaard ratio) was prospectively correlated with angiographic vasospasm. Angiographic vasospasm was independently graded, by observers blinded to the TCD results, as either none, mild (less than one-third artery luminal narrowing), moderate (one-third to one-half narrowing), or severe (more than one-half narrowing). The sensitivity, specificity, likelihood ratios for positive and negative TCD results, positive and negative predictive values, and κ and P values were calculated.RESULTS: One hundred one patients were analyzed in the first part of the study, and 44 patients were analyzed in the second part. Interobserver agreement regarding angiographic vasospasm was good (κ=0.86). Despite significant correlation between mean velocities and the degree of vasospasm, the clinical dependability of TCD velocities (evaluated using predictive values and likelihood ratios) was limited. The positive predictive value of velocities of ≥200 cm/s for moderate/severe angiographic vasospasm was 87% but that of lower velocities was approximately 50%. The negative predictive value of velocities of <120 cm/s was 94% but that of higher velocities was approximately 75%. Only the likelihood ratios for velocities of <120 or ≥200 cm/s were useful (likelihood ratio for negative result=0.17, likelihood ratio for positive result=16.39). Overall, 57% of patients exhibited maximum velocities in the indeterminate range between 120 and 199 cm/s. Lindegaard ratios did not improve the predictive value of TCD monitoring.CONCLUSION: For individual patients, only low or very high middle cerebral artery flow velocities (i.e., <120 or ≥200 cm/s) reliably predicted the absence or presence of clinically significant angiographic vasospasm. Intermediate velocities, which were observed for approximately one-half of the patients, were not dependable and should be interpreted with caution.Key Words: subarachnoid hemorrhage, vasospasmClinicalAB-14484-99Embolic Risk Based on Aortic Atherosclerotic Morphologic Features and Aortic Spontaneous Echocardiographic Contrast—Finkelhor RS (MetroHealth Medical Center, 2500 MetroHealth Dr, Cleveland, OH 44109), Youssefi ME, Lamont WE, Bahler RC—Am Heart J. 1999;137:1088–1093. Copyright ©1999 by Mosby, Inc.Background Different aortic atherosclerotic plaque morphologic features may have varying embolic potentials. Spontaneous echocardiographic contrast (SEC) in the aorta, as in the left atrium, has been associated with an increased risk of embolic events and often occurs with complex aortic atherosclerosis. Thus an evaluation of their isolated and combined association with embolic events was undertaken.Methods We retrospectively studied all patients who underwent biplane or multiplane transesophageal echocardiography meeting the following inclusion and exclusion criteria: age ≥55 years and no other cardiac pathologic condition known to be associated with embolic events other than aortic atherosclerosis or aortic SEC. The 105 patients meeting the criteria were divided into those with aortic atherosclerosis and/or aortic SEC (the study group) and those without these aortic pathologic conditions (the comparison group). Complex aortic atherosclerosis was defined as mobile, ulcerated, or protuberant (>4 mm). SEC was defined as a pulsatile, swirling echo pattern within the aortic lumen. Embolic events included strokes, transient ischemic attacks, or peripheral emboli.Results The 61 study patients and 44 comparison patients did not significantly differ with respect to the reason for referral, age, or sex. Embolic events occurred in 35 patients. Those with ulcerated or mobile plaques had a greater prevalence of embolic events (odds ratio 4.50; 95% confidence interval, 1.30–15.5; P<.05). The highest embolic event rate was seen in patients with any complex atherosclerosis and concomitant SEC (odds ratio 9.00; 95% confidence interval, 2.06–39.3; P<.01). Patients with SEC alone or protuberant plaques alone did not have a higher event rate (odds ratio 1.71 and 0.60; 95% confidence interval, 0.57–5.17 and 0.15–2.47, respectively).Conclusions Embolic events were associated with the presence of ulcerated or mobile aortic plaques. In addition, the combination of aortic SEC and any complex atherosclerosis had the highest embolic association.Key Words: aortic arch, embolismAB-14485-99Posterior Cerebral Artery Territory Infarcts in The New England Medical Center Posterior Circulation Registry—Yamamoto Y, Georgiadis AL, Chang H-M, Caplan LR (Dept of Neurology, Beth Israel Deaconess Medical Center, Dana 779, 330 Brookline Ave, Boston, MA 02215)—Arch Neurol. 1999;56:824–832.Background: Infarcts in the territory of the posterior cerebral arteries (PCAs) are common. Although associated clinical symptoms and signs are known, the mechanisms of stroke and the anatomical distribution of PCA territory lesions caused by the various stroke mechanisms are less well defined. Published reports have selected only special subgroups of patients.Patients and Methods: We studied stroke mechanisms, infarct distribution, and clinical findings among 79 patients in the New England Medical Center Posterior Circulation Registry in whom brain imaging scans showed infarcts that involved 1 or more cortical territories of the PCA.Results: Forty-eight patients (61%) had infarcts limited to the PCA territory (pure PCA), while 31 (39%) also had infarcts in other territories (PCA+). Infarcts were in the cortical territory of the PCA in 47 patients (59%) and were cortical and deep in 32 (41%). Infarcts that were cortical and deep were more common in PCA+ lesions. Stroke mechanisms were embolism of cardiac origin (32 [41%]), proximal arterial disease (25 [32%]), cryptogenic embolism (8 [10%]), intrinsic PCA disease (7 [9%]), vasoconstriction (4 [5%]), and coagulopathy (3 [4%]). Patients with cardiogenic embolism and intrinsic PCA disease often had pure PCA territory infarcts, while patients with proximal arterial disease more often had PCA+ infarcts. Visual abnormalities were present in 66 patients (84%). Motor weakness, cognitive and behavioral abnormalities, and ataxia were found in 20 patients (25%); only 12 (15%) had sensory signs.Conclusions: The great majority of pure PCA and PCA+ territory infarcts are caused by cardiac or intra-arterial embolism. Intrinsic PCA disease, vasoconstriction, and coagulopathy are less common causes of infarction.Key Words: cerebral infarction, posterior cerebral arteryAB-14486-99Association of Cervical Artery Dissection With Recent Infection—Grau AJ (Dept of Neurology, Univ of Heidelberg, Im Neuenheimer Feld 400, 69120 Heidelberg, Germany), Brandt T, Buggle F, Orberk E, Mytilineos J, Werle E, Conradt C, Krause M, Winter R, Hacke W—Arch Neurol. 1999;56:851–856.Background: Cervical artery dissection (CAD) is an important cause of ischemic stroke in younger patients. However, its cause is insufficiently understood.Objective: To test the hypothesis that CAD is frequently associated with recent infection.Subjects and Methods: We compared the prevalence of infection during the preceding week in 43 consecutive patients with acute CAD and 58 consecutive patients younger than 50 years with acute cerebral ischemia from other causes (control patients). In subgroups of patients, we correlated infectious status with electron microscopic studies of skin biopsy specimens and investigated pathways potentially linking infection and CAD.Results: Recent infection was more common in patients with CAD (25/43 [58.1%]) than in control patients (19/58 [32.8%]; P=.01). Respiratory tract infection was preponderant in both groups. Recent infection, but not the mechanical factors cough, sneezing, or vomiting, was independently associated with CAD in multivariate analysis. Investigation of serum antibodies against Chlamydia pneumoniae, smooth muscle cells, endothelial cells, collagen types I through IV, and heat shock protein 65 and assessment of serum α1-antitrypsin and HLA did not contribute to the understanding of the pathogenesis of CAD. More patients with pathologic findings in skin biopsy specimens tended to have had a recent infection (13/21 [62%]) than patients without pathologic findings (2/9 [22%]; P=.11).Conclusion: Our results suggest a significant association between recent infection and CAD that is not explained by mechanical factors occurring during infection.Key Words: dissection, infectionAB-14487-99Importance of Left Atrial Appendage Flow as a Predictor of Thromboembolic Events in Patients With Atrial Fibrillation—Kamp O (Free Univ Hospital, Dept of Cardiology, De Boelelaan 1117, 1081 HV Amsterdam, Netherlands), Verhorst PMJ, Welling RC, Visser CA—Eur Heart J. 1999;20:979–985. Copyright ©The European Society of Cardiology.Aim The purpose of this study was to investigate the role of transoesophageal echocardiography in predicting subsequent thromboembolic events in patients with atrial fibrillation.Methods and patients Transoesophageal echocardiography was performed in 88 patients with documented paroxysmal (n=53) or chronic atrial fibrillation (n=35) to assess morphological and functional predictors of thromboembolic events. Prospective selection was from patients with non-valvular atrial fibrillation who had undergone transoesophageal echocardiography because of previous thromboembolism (n=30); prior to electrical cardioversion (n=31); or for other reasons (n=27). All patients were followed up for 1 year.Results During the period of follow-up new thromboembolic events occurred in 18 of 88 patients (20%/year); 16 of these patients had a stroke and two a peripheral embolism. Univariate analysis revealed that previous thromboembolism (P<0.005; odds ratio 5.3 [CI 1.9, 12.1]), history of hypertension (P<0.01; odds ratio 4.0 [CI 1.4, 10.4]), presence of left atrial spontaneous echo contrast (P<0.025; odds ratio 3.5 [CI 1.2, 10.0]), and presence of left atrial appendage peak velocity ≤0.20 m.s−1 (P<0.01; odds ratio 4.1 [CI 1.4, 11.6]) were significantly related to subsequent thromboembolic events. Stepwise logistic regression showed that independent predictors of thromboembolic events were: history of thromboembolism (P<0.005), history of hypertension (P<0.05) and low left atrial appendage peak velocity ≤0.20 m.s−1 (P<0.01).Conclusions In patients with atrial fibrillation, the presence of spontaneous echo contrast in the left atrium, and in particular a low left atrial appendage peak flow velocity, can be used to identify a subgroup of atrial fibrillation patients at either increased or decreased risk of subsequent thromboembolism, which might have important implications for anticoagulation therapy.Key Words: embolism, atrial fibrillationAB-14488-99The Natural History of Cavernous Malformations: A Prospective Study of 68 Patients—Moriarity JL, Wetzel M, Clatterbuck RE, Javedan S, Sheppard J-M, Hoenig-Rigamonti K, Crone NE, Breiter SN, Lee RR, Rigamonti D (Neurovascular Surgery, The Johns Hopkins Hospital, 600 N Wolfe St, Meyer 5-181, Baltimore, MD 21287)—Neurosurgery. 1999;44:1166–1173.OBJECTIVE: Cavernous malformations are angiographically occult cerebrovascular malformations found in approximately 0.5% of the population. To help further understand the natural history of these lesions, we prospectively followed 68 patients harboring cavernous malformations.METHODS: The 68 patients in this study were all diagnosed radiographically (67 patients) or surgically (1 patient) and were entered into a patient database. Age, sex, clinical symptoms, seizure frequency, focal neurological deficits, and presence or absence of extralesional hemorrhage were all recorded at presentation. Patients were then followed prospectively to determine the rate of hemorrhage and new-onset seizures.RESULTS: The mean follow-up per patient was 5.2 years, and the total follow-up was 352.9 patient-years. There was an average of 3.4 lesions per patient. Thirteen of the patients (19%) had familial cavernous malformations. Patients with familial disease were more likely to have multiple lesions than patients with sporadic disease (85% versus 25%, respectively [P=0.001]). Initial presentation included headache (65%), seizures (49%), and focal neurological deficit (46%). Eleven symptomatic, radiologically proven, extralesional hemorrhages occurred during the 352.9 patient-years of follow-up for an overall hemorrhage rate of 3.1% per patient-year. Female patients had a significantly higher prospective hemorrhage rate (4.2% per patient-year versus 0.9% per patient-year [P=0.04]). A history of hemorrhage at presentation was not a risk factor for subsequent hemorrhage during follow-up. The rate of new-onset seizures was 2.4% per patient-year.CONCLUSION: The clinical presentation and prospective hemorrhage rate reported here agree well with findings of other prospective studies. This information, combined with our new-onset seizure rate, should aid clinicians caring for patients with cavernous malformations.Key Words: cavernous angiomas, natural historyEpidemiologyAB-14489-99Effects of Leisure-Time Physical Activity and Ventilatory Function on Risk for Stroke in Men: The Reykjavík Study—Agnarsson U (The Heart Preventive Clinic, Lagmuli 9, 108 Reykjavík, Iceland), Thorgeirsson G, Sigvaldason H, Sigfusson N—Ann Intern Med. 1999;130:987–990. Copyright ©1999 American College of Physicians–American Society of Internal Medicine.Background: Stroke is a major cause of illness, death, and health expenditures. Leisure-time physical activity may reduce the risk for stroke.Objective: To examine the association of leisure-time physical activity and pulmonary function with risk for stroke.Design: Prospective cohort study.Setting: Reykjavík, Iceland.Participants: 4484 men 45 to 80 years of age followed for a mean (±SD) of 10.6±3.6 years.Measurements: Patients underwent physical examination, blood sampling, and spirometry and completed a questionnaire about health and exercise. Computerized hospital records were used to identify strokes, and the Icelandic National Registry was used to identify deaths.Results: New stroke developed in 249 men (5.6%) (hemorrhagic stroke in 44 [18%] and ischemic stroke in 205 [82%]). In a multivariable hazard analysis that controlled for known risk factors for cerebrovascular disease, leisure-time physical activity maintained after 40 years of age was associated with a reduced risk for stroke (relative risk, 0.69 [CI, 0.47 to 1.01] for total stroke and 0.62 [CI, 0.40 to 0.97] for ischemic stroke). Risk for stroke increased with diminished ventilatory function (FVC or FEV1) (relative risk, 1.9 [CI, 1.06 to 3.25] for the lowest compared with the highest quintile).Conclusion: Middle-aged men who participate in leisure-time physical activity and have good pulmonary function seem to have a lower risk for stroke than men who are not active or have diminished pulmonary function.Key Words: risk factors, stroke preventionAB-14490-99Relation of Consumption of Vitamin E, Vitamin C, and Carotenoids to Risk for Stroke Among Men in the United States—Ascherio A (Dept of Nutrition, Harvard School of Public Health, 665 Huntington Ave, Boston, MA 02115), Rimm EB, Hernán MA, Giovannucci E, Kawachi I, Stampfer MJ, Willett WC—Ann Intern Med. 1999;130:963–970. Copyright ©1999 American College of Physicians–American Society of Internal Medicine.Background: Antioxidants increase the resistance of low-density lipoprotein to oxidation and may thereby reduce risk for atherosclerosis.Objective: To determine whether intake of vitamin E, vitamin C, or carotenoids predict risk for total or ischemic stroke.Design: Prospective observational study.Setting: The Health Professionals Follow-up Study.Participants: 43 738 men 40 to 75 years of age who did not have cardiovascular disease or diabetes.Measurements: Repeated and validated dietary assessments were done by using a self-administered 131-item food-frequency questionnaire, which included questions on dose and duration of vitamin supplement use. The follow-up period was 8 years.Results: A total of 328 strokes occurred: 210 ischemic, 70 hemorrhagic, and 48 unclassified. After adjustment for age, smoking, hypertension, hypercholesterolemia, body mass index, physical activity, parental history of myocardial infarction, alcohol consumption, and total energy intake, the relative risk for ischemic stroke in the top quintile of vitamin E intake (median, 411 IU/d) compared with the bottom quintile (5.4 IU/d) was 1.18 (95% CI, 0.77 to 1.82). The relative risk for ischemic stroke in the top quintile of vitamin C intake (1167 mg/d) compared with the bottom quintile (95 mg/d) was 1.03 (CI, 0.66 to 1.59). Results for total stroke were similar. Associations of vitamin intake with hemorrhagic stroke were also nonsignificant, but the CIs were wide. Neither dose nor duration of vitamin E or vitamin C supplement use was related to risk for total or ischemic stroke. The relative risk for ischemic stroke was 1.16 (CI, 0.81 to 1.67) in men using 250 IU or more of vitamin E supplementation per day compared with men who used no vitamin E supplements and was 0.93 (CI, 0.60 to 1.45) in men using 700 mg or more of vitamin C supplementation per day compared with men who used no vitamin C supplements. A significant inverse relation between lutein intake and risk for ischemic stroke was seen but was not independent of other dietary factors.Conclusion: Vitamin E and vitamin C supplements and specific carotenoids did not seem to substantially reduce risk for stroke in this cohort. Modest effects, however, cannot be excluded.Key Words: stroke prevention, vitaminsExperimental PathologyAB-14491-99Interrelation Between Cerebral Energy Metabolism and Behaviour in a Rat Model of Permanent Brain Vessel Occlusion—Plaschke K, Yun S-W, Martin E, Hoyer S, Bardenheuer HJ (Clinic of Anesthesiology, Univ of Heidelberg, Im Neuenheimer Feld 110, D-69120 Heidelberg, Germany)—Brain Res. 1999;830:320–329. Copyright ©1999 Elsevier Science.The present study investigates the interrelation between cerebral energy metabolism and memory capacities after acute and permanent occlusions of carotid and vertebral arteries in adult Wistar rats (n=60). Tissue ATP, phosphocreatine, ADP, AMP and adenosine concentrations were determined in rat brain by high-pressure liquid chromatography (HPLC) analysis. Lactate and pyruvate were measured spectrophotometrically. Rats underwent psychometric testing by means of a holeboard test, closed field activity, and passive avoidance behavior. Acute cerebral ischemia was associated with a substantial deficit in energy load (−50%). Cortical adenosine and lactate exhibited a 7- and a 10-fold increase, respectively, in concentration. After 2 weeks of four-vessel occlusion, cortical ATP and phosphocreatine showed a partial enhancement in their concentrations if compared with acute ischemia. Consequently, energy load (μmol/g) increased from 0.59 to 1.42 in cerebral cortex and from 0.58 to 1.14 in hippocampus under conditions of acute and permanent ischaemia, respectively. While lactate was normalized, adenosine showed a 2-fold increase in its cortical concentration. All animals improved their abilities in learning, memory and cognition after a 7-day training period. Acute vessel occlusion severely decreased working memory (WM), reference memory (RM) and locomotor activity. Simultaneously, the passive avoidance test showed a significant reduction in latency time from 247±85 s (sham) to 145±132 s. The partial improvement in brain energy state was accompanied by a relative improvement in WM and RM, although both memory capacities remained significantly lower than in controls. The data of the present study demonstrate a linear relationship between cerebral energy metabolism and brain memory capacities after acute and permanent vessel occlusions in rats.Key Words: cerebral ischemia, focal, stroke, experimentalAB-14492-99Post-Treatment With an Inhibitor of Poly (ADP-Ribose) Polymerase Attenuates Cerebral Damage in Focal Ischemia—Takahashi K, Pieper AA, Croul SE, Zhang J, Snyder SH, Greenberg JH (Cerebrovascular Research Center, Dept Neurology, Univ of Pennsylvania, School of Medicine, 429 Johnson Pavilion, 3610 Hamilton Walk, Philadelphia, PA 19104-6063)—Brain Res. 1999;829:46–54. Copyright ©1999 Elsevier Science B.V.Poly(ADP-ribose) polymerase (PARP) is thought to play a physio-logical role in maintaining genomic integrity and in the repair of DNA strand breaks. However, the activation of PARP by free radical-damaged DNA plays a pivotal role in mediating ischemia-reperfusion injury. The excessive activation of PARP causes a rapid depletion of intracellular energy leading to cell death. The present study examined the effect of post-ischemic pharmacological inhibition of PARP in a rat focal cerebral ischemia model. In Long–Evans rats, focal cerebral ischemia was produced by cauterization of the right distal middle cerebral artery (MCA) with bilateral temporary common carotid artery (CCA) occlusion for 90 min. A PARP inhibitor, 3,4-dihydro-5-[4-(1-piperidinyl)butoxyl]-1(2H)-isoquinolinone (DPQ; IC50=1 μM/1) was injected i.p. 30 min after the onset of MCA occlusion (control: 10, 20, 40 and 80 mg/kg; n=7 each). Twenty-four hours later, the total infarct volume was measured. Regional blood flow in the right parietal cortex decreased to approximately 20% of the baseline following MCA occlusion in all groups. PARP inhibition lead to a significant decrease in damaged volume in all treated groups with the largest reduction in the 40 mg/kg group (111.5±24.8 mm3, mean±SD, p<0.01), compared to the control group (193.5±28.6 mm3). We also found there was a significant increase of poly(ADP-ribose) immunoreactivity in the ischemic region, as compared to the contralateral side, with DPQ treatment diminishing poly(ADP-ribose) production. These findings indicate that DPQ exerts its neuroprotective effects in vivo by PARP inhibition and that PARP inhibitors may be effective for treating ischemic stroke, even when the treatment is initiated after the onset of ischemia.Key Words: cerebral ischemia, focal, stroke, experimentalAB-14493-99Reduction of Ischemic Brain Injury by Anti-P-Selectin Monoclonal Antibody After Permanent Middle Cerebral Artery Occlusion in Rat—Suzuki H, Abe K (Dept of Neurology, Okayama Univ Medical School, 2-5-1 Shikatacho, Okayama 700-8558, Japan), Tojo SJ, Kitagawa H, Kimura K, Mizugaki M, Itoyama Y—Neurol Res. 1999;21:269–276.The selectin family of adhesion molecules is involved in adhesion of leukocyte to microcirculatory system and the transmigration into brain parenchyma. Although the role of P-selectin may be important in the pathogenesis of brain ischemia, a possible protective effect on ischemic brain injury by blocking P-selectin has not been reported. We have examined the effects of a novel anti-P-selectin antibody on ischemic brain injury after 24 h of permanent middle cerebral artery occlusion (MCAO) in rat. Male Wistar rats were subjected to MCAO by an insertion of a silicone rubber cylinder for 24 h. Anti-rat P-selectin monoclonal antibody, ARP 2-4, was injected intravenously at a dose of 1 mg kg−1 at 5 min before the induction of MCAO. Control animals received the same volume of vehicle solution. Regional cerebral blood flow (rCBF) was measured immediately after and at 8 h of MCAO. At decapitation of rats at 24 h of permanent MCAO, infarct size was compared between the antibody and vehicle treated group. In addition, immunohistochemistry for leukocyte infiltration and HSP72, and histochemistry for TUNEL were also compared. Pretreatment with ARP 2-4 improved rCBF at 8 h of MCAO (55.4%±11.7% of control, n=5) as compared to vehicle group (24.2%±11.8%, n=5, p<0.02). Although leukocyte infiltration was not normally detected by monoclonal antibodies for CD11a and CD18, it became remarkably evident at 1 day of MCAO. Although HSP72 and TUNEL were not also detected in sham control brains, they were induced in neurons of the MCA area at 1 day of MCAO. Treatment with ARP 2-4 significantly reduced the numbers of leukocyte and neurons with positive HSP72 and TUNEL stainings. These results demonstrated that an administration of a monoclonal antibody against P-selectin improved rCBF, and attenuated infarct size that was associated with reduction of leukocyte infiltration. Furthermore, treatment with the antibody reduced both HSP72 and TUNEL stainings. These data suggest an important role of P-selectin in ischemic brain damage, and a future therapeutic potential to human stroke patients.Key Words: cerebral ischemia, focal, stroke, experimentalAB-14494-99Carvastatin Suppresses Intimal Thickening of Rabbit Carotid Artery After Balloon Catheter Injury Probably Through the Inhibition of Vascular Smooth Muscle Cell Proliferation and Migration—Komukai M (Dept of Bioscience Research, Senga Pharmaceutical Laboratory Inc, 3-5-12, Higashi-Ome, Ome City, Tokyo 198-0042 Japan), Saitoh-Wajima Y, Tashiro J, Shinomiya M, Saito Y, Morisaki N—Scand J Clin Lab Invest. 1999;59:159–166.In order to test whether a 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitor has an anti-atherogenic activity, the effects of carvastatin, a newly developed potent inhibitor, and pravastatin were examined on the intimal thickening of the artery after the endothelial denudation induced by balloon catheter injury. Rabbits were divided into four groups; control, pravastatin-treated (20 mg kg−1 day−1) and two of carvastatin-treated groups (10 or 20 mg kg−1 day−1). Two weeks after balloon catheter injury, the areas of intima and media of the injured carotid arteries were determined, and the ratios of intima to media (I/M) were calculated as an index of intimal thickening. Average I/M ratios of the injured artery were 0.42±0.05 for control, 0.49±0.07 for pravastatin, 0.19±0.03 (10 mg kg−1 day−1) and 0.20±0.04 (20 mg kg−1 day−1) for carvastatin-treated rabbits, respectively. Thus, carvastatin reduced I/M ratio of the injured artery to approximately half versus control, but pravastatin failed to suppress the intimal thickening. For in vitro study, vascular smooth muscle cells (SMC) from rabbit aorta were explanted, then cultured, and the effects of carvastatin on SMC migration and SMC p