Abstracts of Literature

Abstract

HomeStrokeVol. 31, No. 5Abstracts of Literature Free AccessOtherPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyRedditDiggEmail 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 May 2000https://doi.org/10.1161/01.STR.31.5.1199Stroke. 2000;31:1199–1205Cerebral AneurysmsAB-14661-00Disturbance of Cerebral Blood Flow Autoregulation in Hypertension is Attributable to Ischaemia Following Subarachnoid Haemorrhage in Rats: A PET Study—Yamamoto S (Dept of Neurosurgery, Hamamatsu Univ School of Medicine, 3600 Handa-cho, Hamamatsu 431-3192, Japan), Teng W, Kakiuchi T, Tsukada H—Acta Neurochir (Wien). 1999;141:1213–1219. Copyright © 1999 Springer-Verlag.The effects of subarachnoid haemorrhage (SAH) on cerebral blood flow (CBF) autoregulation during induced hypertension were studied by positron emission tomography (PET) during chronic vasospasm in anaesthetized Sprague-Dawley rats. SAH was induced by intracisternal injection of autologous blood. In the control animals saline was injected instead. This method produced angiographical vasospasm of major arteries 48 h after injection. During this period, CBF was measured at each side of fronto-parietal and occipital sections using PET with or without induced hypertension. Mean arterial blood pressure (MABP) was increased from 94±2.4 to 140±0.3 mm Hg by the injection of phenylephrine. An autoregulatory index (AI) expressed as delta CBF (%) per 10-mm Hg increase in MABP was employed to analyse CBF response. SAH significantly reduced (p<0.0001) basal CBF (ml/100 g/min) by 26.2% (control 60.0±1.9 n=24, SAH 44.3±4.5 n=20). A territorial CBF that decreased by 50% or more over the mean control value was used to define ischaemia and was identified in five out of 20 regions (25%) in the SAH group. AI (%/10-mm Hg) was 13.5±2.4 in the control group (n=24). In the SAH group, AI decreased (p<0.05) to 4.5±2.5 in non-ischaemic areas (n=15), while in the ischaemic areas (n=5) AI increased (p<0.05) to 25.2±4.1. Since the spastic artery is intrinsically resistant to hypertension, the marked increase in CBF during hypertension can be attributable to ischaemia following SAH.Key Words: cerebral blood flow, subarachnoid hemorrhageAB-14662-00Increased Cerebral Blood Flow but No Reversal or Prevention of Vasospasm in Response to l-Arginine Infusion After Subarachnoid Hemorrhage—Pluta RM (NINDS, Surgical Neurology Branch NIH, Bldg 10, Rm 5D-37, 9000 Rockville Pike, Bethesda, MD 20892), Afshar JKB, Thompson BG, Brook RJ, Harvey-White J, Oldfield EH—J Neurosurg. 2000;92:121–126.Objective. The reduction in the level of nitric oxide (NO) is a purported mechanism of delayed vasospasm after subarachnoid hemorrhage (SAH). Evidence in support of a causative role for NO includes the disappearance of nitric oxide synthase (NOS) from the adventitia of vessels in spasm, the destruction of NO by hemoglobin released from the clot into the subarachnoid space, and reversal of vasospasm by intracarotid NO. The authors sought to establish whether administration of l-arginine, the substrate of the NO-producing enzyme NOS, would reverse and/or prevent vasospasm in a primate model of SAH.Methods. The study was composed of two sets of experiments: one in which l-arginine was infused over a brief period into the carotid artery of monkeys with vasospasm, and the other in which l-arginine was intravenously infused into monkeys over a longer period of time starting at onset of SAH. In the short-term infusion experiment, the effect of a 3-minute intracarotid infusion of l-arginine (intracarotid concentration 10−6 M) on the degree of vasospasm of the right middle cerebral artery (MCA) and on regional cerebral blood flow (rCBF) was examined in five cynomolgus monkeys. In the long-term infusion experiment, the effect of a 14-day intravenous infusion of saline (control group, five animals) or l-arginine (10−3 M; six animals) on the occurrence and degree of cerebral vasospasm was examined in monkeys. The degree of vasospasm in all experiments was assessed by cerebral arteriography, which was performed preoperatively and on postoperative Days 7 (short and long-term infusion experiments) and 14 (long-term infusion experiment). In the long-term infusion experiment, plasma levels of l-arginine were measured at these times in the monkeys to confirm l-arginine availability.Vasospasm was not affected by the intracarotid infusion of l-arginine (shown by the reduction in the right MCA area on an anteroposterior arteriogram compared with preoperative values). However, intracarotid l-arginine infusion increased rCBF by 21% (p<0.015; PCO2 38–42 mm Hg) in all vasospastic monkeys compared with rCBF measured during the saline infusions. In the long-term infusion experiment, vasospasm of the right MCA occurred with similar intensity with or without continuous intravenous administration of l-arginine on Day 7 and had resolved by Day 14. The mean plasma l-arginine level increased during infusion from 12.7±4 μg/ml on Day 0 to 21.9±13.1 μg/ml on Day 7 and was 18.5±3.1 μg/ml on Day 14 (p<0.05).Conclusions. Brief intracarotid and continuous intravenous infusion of l-arginine did not influence the incidence of degree of cerebral vasospasm. After SAH, intracarotid infusion of l-arginine markedly increased rCBF in a primate model of SAH. These findings discourage the use of l-arginine as a treatment for vasospasm after SAH.Key Words: subarachnoid hemorrhage, vasospasmAB-14663-00Toward More Rational Prediction of Outcome in Patients With High-Grade Subarachnoid Hemorrhage—Chiang VLS, Claus EB, Awad IA (Dept of Neurosurgery, Yale Medical School, 333 Cedar St, TMP 405, New Haven, CT 06520)—Neurosurgery. 2000;46:28–36.OBJECTIVE: Accurate outcome prediction after high-grade subarachnoid hemorrhage remains imprecise. Several clinical grading scales are in common use, but the timing of grading and changes in grade after admission have not been carefully evaluated. We hypothesized that these latter factors could have a significant impact on outcome prediction.METHODS: Fifty-six consecutive patients with altered mental status after subarachnoid hemorrhage, who were managed at a single institution, were studied retrospectively. On the basis of prospectively assessed elements of the clinical examination, each patient was graded at admission, at best before treatment, at worst before treatment, immediately before treatment, and at best within 24 hours after treatment of the aneurysm using the Glasgow Coma Scale (GCS), the World Federation of Neurological Surgeons (WFNS) scale, and the Hunt and Hess scale. Outcome at 6 months was determined using a modification of the Glasgow Outcome Scale validated against the Karnofsky scale. All grades and clinical and radiographic data collected were compared among good and poor outcome groups. Multivariate analyses were then performed to determine which grading scale, which time of grading, and which other factors were correlated with and contributed significantly to outcome prediction.RESULTS: A good outcome was achieved in 24 (43%) of 56 patients. Our study also had a 32% mortality rate. With the Hunt and Hess scale, only the worst pretreatment grade was significantly correlated with outcome. However, with the GCS and the WFNS scale, grading at all pretreatment times was significantly correlated with outcome, although outcome was best predicted before treatment, regardless of the scale used, if grading was performed at the patient’s clinical worst. Multivariate analysis revealed that the best predictor of outcome was WFNS grade at clinical worst before treatment. Used alone, a WFNS Grade 3 at worst pretreatment predicted a 75% favorable outcome, and a WFNS Grade 5 at worst pretreatment predicted an 87% poor outcome. No significant correlation was found between direction or magnitude of change in grade and outcome. Age was found to be significantly correlated with outcome, but it was only an independent factor in outcome prediction when used in conjunction with the Hunt and Hess scale and not with the WFNS scale and the GCS.CONCLUSION: Timing of grading is an important factor in outcome prediction that needs to be standardized. This study suggests that the patient’s worst clinical grade is most predictive of outcome, especially when the patient is assessed using the WFNS scale or the GCS.Key Words: subarachnoid hemorrhage, stroke outcomeAB-14664-00Factors Associated With Aneurysm Size in Patients With Subarachnoid Hemorrhage: Effect of Smoking and Aneurysm Location—Qureshi AI (Dept of Neurosurgery, Millard Fillmore Hospital, 3 Gates Circle, Buffalo, NY 14209-1194), Sung GY, Suri MFK, Straw RN, Guterman LR, Hopkins LN, and Participants—Neurosurgery. 2000;46:44–50.OBJECTIVE: Intracranial aneurysm size is an important determinant of risk of rupture and outcome after rupture. Risk factors influencing aneurysm formation and growth are not well defined. In this study, we examined the association between known risk factors for cerebrovascular disease and size of intracranial aneurysms in patients with aneurysmal subarachnoid hemorrhage.METHODS: We analyzed prospectively collected data from the placebo-treated group in a multicenter clinical trial conducted at 54 neurosurgical centers in North America. The presence, location, and size of intracranial aneurysms were determined by review of the admission angiograms. Pertinent information regarding the presence of various cerebrovascular risk factors was collected for each patient. Using logistic regression analysis, we identified independent determinants of aneurysm size from demographic, clinical, and angiographic characteristics of the participants. The impact of aneurysm size on 3-month mortality was analyzed after adjusting for potential confounding factors.RESULTS: For 298 patients admitted with subarachnoid hemorrhage, the ruptured aneurysms were graded as small (<13 mm) in 235 patients (79%) and large (≥13 mm) in 63 patients (21%). In the logistic regression model, both smoking at any time (odds ratio, 2.2; 95% confidence interval, 1.1–4.5) and middle cerebral artery origin (odds ratio, 2.5; 95% confidence interval, 1.3–4.9) were independently associated with large aneurysms. Neither hypertension, diabetes mellitus, nor alcohol and illicit drug use were associated with large-sized aneurysms. After adjusting for initial Glasgow Coma Scale score and age in the logistic regression model, the presence of large-sized aneurysms was independently associated with 3-month mortality (odds ratio, 2.3; 95% confidence interval, 1.1–4.8).CONCLUSION: Cigarette smoking and middle cerebral artery origin seem to increase the risk for developing large aneurysms in patients predisposed to intracranial aneurysm formation. Further studies are required to investigate the mechanism underlying the association between cigarette smoking and intracranial aneurysm formation.Key Words: subarachnoid hemorrhage, aneurysmsClinicalAB-14665-00Lacunar Infarcts in Patients Aged 85 Years and Older—Arboix A (Acute Stroke Unit, Dept of Neurology, Hospital del Sagrat Cor, Viladomat 288, E-08029 Barcelona, Spain), Garcia-Eroles L, Massons J, Oliveres M, Targa C—Acta Neurol Scand. 2000;101:25–29. Copyright © Munksgaard 2000.Objectives—To compare the occurrence of lacunar infarcts in the very elderly (>85 years of age) and in patients below 85. Material and methods—Data of 374 consecutive patients with lacunar infarcts were collected from a prospective hospital-based stroke registry in which 2000 patients are included. Distinctive clinical features of lacunar infarct in the very elderly were assessed by multiple logistic regression analysis. Results—Lacunar infarcts were diagnosed in 39 (15%) of the 262 very elderly patients of our stroke registry. Lacunar infarcts in the very elderly accounted for 10.5% of all lacunes. There was no statistical difference in the occurrence of different lacunar syndromes between the very elderly patients and patients below 85. However, the very old group with lacunar infarct showed a significantly higher proportion of the female sex (56.4% vs 37.3%) and history of atrial fibrillation (28.2% vs 8.7%), chronic renal disease and pathologic condition and a significantly lower proportion of hypertension (61.5% vs 77.3%), diabetes (7.7% vs 28.4%), ischemic heart disease, hypercholesterolemia, and absence of neurologic deficit at discharge from the hospital than patients below 85. After multivariate analysis only atrial fibrillation (OR=3.77), female gender (OR=2.52), hypertension (OR=0.35), and diabetes (OR=0.16) were independent clinical factors for developing lacunar infarction in the very elderly. Conclusion—In the very elderly the higher occurrence of atrial fibrillation, the lower prevalence of hypertension and diabetes, and the greater focal neurological impairment suggest that the cardioembolic pathogenetic mechanisms may be more frequent than generally established for lacunar infarcts in stroke patients.Key Words: aged, lacunar infarctionAB-14666-00Emotional Outcomes After Stroke: Factors Associated With Poor Outcome—Dennis M (Neurosciences Trials Unit, Dept of Clinical Neurosciences, The Univ of Edinburgh, Bramwell Dott Bldg, Western General Hospital, Crewe Rd, Edinburgh, EH4 2XU, UK), O’Rourke S, Lewis S, Sharpe M, Warlow C—J Neurol Neurosurg Psychiatry. 2000;68:47–52.Objectives—The impact of stroke on the emotional outcome of patients is large. The aim was to describe the emotional outcomes among a cohort of patients which was of sufficient size to provide a precise estimate of their frequency and help identify those factors which are associated with poor outcomes after an acute stroke.Methods—372 surviving patients, who had been referred to a hospital and entered into a randomised trial to evaluate a stroke family care worker, were asked to complete questionnaires at a 6 month follow up. These included measures of emotional distress (general health questionnaire 30 item, hospital anxiety and depression scale) and physical functioning (modified Rankin, Barthel index). A regression analysis was used to identify factors which were independently associated with poor outcomes.Results—184 (60%) surviving patients scored more than 4 on the GHQ-30, 55 (22%) more than 8 on the HAD anxiety subscale, and 49 (20%) more than 8 on the HAD depression subscale. Patients with severe strokes resulting in physical disability were more likely to be depressed whereas there was a less strong relation between disability and anxiety. Patients with posterior circulation strokes had consistently better emotional outcomes than those with anterior circulation strokes.Conclusions—These data may help identify those patients at greatest risk of poor emotional outcomes and thus help in planning trials and delivering appropriate interventions.Key Words: stroke outcome, depressionAB-14667-00Stroke in Children: The Coexistence of Multiple Risk Factors Predicts Poor Outcome—Lanthier S, Carmant L (Dept of Pediatrics, Div of Neurology, Hôpital Sainte-Justine, 3175 Chemin de la Côte Sainte-Catherine, Laboratoire d’Életrophysiologie Médicale Rm 2130, Montréal, Québec, Canada, H3T 1C5), David M, Larbrisseau A, de Veber G—Neurology. 2000;54:371–378. Copyright © 2000 by the American Academy of Neurology.Objective: To characterize the risk factors for stroke in children and their relationship to outcomes. Methods: We reviewed charts of children with ischemic and hemorrhagic stroke seen at Hôpital Sainte-Justine, Montréal between 1991 and 1997. Results: We found 51 ischemic strokes: 46 arterial and 5 sinovenous thromboses. Risk factors were variable and multiple in 12 (24%) of the 51 ischemic strokes. Ischemic stroke recurred in 3 (8%) patients with a single or no identified risk factor and in 5 (42%) of 12 patients with multiple risk factors (p=0.01). We also found 21 hemorrhagic strokes, 14 (67%) of which were caused by vascular abnormalities. No patient with hemorrhagic stroke had multiple risk factors. Hemorrhagic stroke recurred in two patients (10%). Outcome in all 72 stroke patients was as follows: asymptomatic, 36%; symptomatic epilepsy or persistent neurologic deficit, 45%; and death, 20%. Death occurred more frequently in patients with recurrent stroke (40%) than in those with nonrecurrent stroke (16%). Conclusions: Multiple risk factors are found in many ischemic strokes and may predict stroke recurrence. Recurrent stroke tends to increase rate of mortality. Because of the high prevalence and importance of multiple risk factors, a complete investigation, including hematologic and metabolic studies and angiography, should be considered in every child with ischemic stroke, even when a cause is known.Key Words: stroke outcome, childAB-14668-00Incidence and Prognostic Significance of Fever Following Intracerebral Hemorrhage—Schwarz S (Dept of Neurology, Univ of Heidelberg, 400 Im Neuenheimer Feld, Heidelberg 69120, Germany), Häfner K, Aschoff A, Schwab S—Neurology. 2000;54:354–361. Copyright © 2000 by the American Academy of Neurology.Objective: To investigate the incidence and prognostic significance of fever on presentation and during the subsequent 72 hours in patients with spontaneous supratentorial intracerebral hemorrhage (ICH). Methods: We analyzed 251 patients. On admission, body temperature, Glasgow Coma Scale (GCS) score, age, sex, blood pressure, blood glucose level, and presumed origin of hemorrhage were analyzed. From the initial CT scan, hematoma volume, location, and presence of intraventricular hemorrhage were determined. From the first 72 hours, hematoma enlargement, duration of increased temperatures, blood pressure, and blood glucose level were determined. Outcome was classified on discharge with the Glasgow Outcome Scale (GOS) score. Results: Outcomes included no symptoms in 23 (9%), moderate disability in 64 (26%), severe disability in 104 (41%), vegetative state in 5 (2%), and death in 55 (22%) patients. Prognostic factors retained from a logistic regression model with a dichotomized GOS scale (GOS score of 1 or 2 versus GOS score of 3 to 5) as response variables were GCS score of 7 or less, age older than 75 years, hematoma volume of more than 60 cm3, ventricular hemorrhage, and presence of a coagulation disorder (p<0.05). Fever was associated with intraventricular hemorrhage. From 196 patients, data from the first 72 hours were analyzed. A total of 18 patients (9%) had normal temperatures throughout the study. The duration of fever (≥37.5 °C) was less than 24 hours in 66 (34%), 24 to 48 hours in 70 (36%), and more than 48 hours in 42 patients (21%). Independent prognostic factors during the first 72 hours were duration of fever, secondary hemorrhage, GCS score of 7 or less, ventricular hemorrhage, hematoma volume of more than 60 cm3, duration of increased blood pressure of more than 48 hours, and duration of increased blood glucose of more than 48 hours. Conclusions: The incidence of fever after supratentorial ICH is high, especially in patients with ventricular hemorrhage. In patients surviving the first 72 hours after hospital admission, the duration of fever is associated with poor outcome and seems to be an independent prognostic factor in these patients.Key Words: intracerebral hemorrhage, hyperthermiaEpidemiologyAB-14669-00Cardiovascular and Cerebrovascular Mortality Associated With Ocular Pseudoexfoliation—Shrum KR (Ophthalmology Dept, 200 SW 1st St, Rochester, MN 55905), Hattenhauer MG, Hodge D—Am J Ophthalmol. 2000;129:83–86. Copyright © 2000 by Elsevier Science Inc.purpose: In recent years, several studies have shown the presence of vascular, cardiac, and other organ pseudoexfoliative material in patients with ocular pseudoexfoliation. The purpose of this study was to determine whether an association exists between ocular pseudoexfoliation and cardiovascular, cerebrovascular, or all-cause mortality.methods: This retrospective study included 472 residents of Olmsted County, Minnesota, who were diagnosed with pseudoexfoliation syndrome or pseudoexfoliative glaucoma at Mayo Clinic from 1976 through 1995. Of these 472 cases, 151 subsequently died from 1976 through 1997. Cause of death for these patients, as determined by the National Center for Health Statistics was compared with the entire Rochester, Minnesota, population using Kaplan-Meier analysis.results: Of the 472 patients with ocular pseudoexfoliation, 358 (76%) were female and 114 (24%) were male. The mean age at diagnosis was 74 years, with a SD of 10 years and a range from 39 to 106 years. Cardiovascular disease resulted in 40 deaths, with a 15-year cumulative probability of cardiovascular mortality of 22%, compared with an expected 20% (no significant difference with P=.19). Cerebrovascular disease resulted in 26 deaths with a 15-year cumulative probability of cerebrovascular mortality of 12%, compared with an expected 10% (no significant difference with P=.38). Finally, the 15-year observed all-cause cumulative mortality was 53% versus an expected rate of 59% (significant difference with P=.0002).conclusions: No association was found between ocular pseudoexfoliation and cardiovascular or cerebrovascular mortality. All-cause mortality was significantly less in patients with ocular pseudoexfoliation.Key Words: ocular disease, mortalityAB-14670-00J-Shaped Relation Between Blood Pressure and Stroke in Treated Hypertensives—Vokó Z, Bots ML, Hofman A, Koudstaal PJ, Witteman JCM, Breteler MMB (Erasmus Univ, School of Medicine, Dept of Epidemiology & Biostatistics, POB 1738, NL-3000 Dr, Rotterdam, Netherlands)—Hypertension. 1999;34:1181–1185.The objective of this study was to investigate the relationship between hypertension and risk of stroke in the elderly. The study was performed within the framework of the Rotterdam Study, a prospective population-based cohort study. The risk of first-ever stroke was associated with hypertension (relative risk, 1.6; 95% CI, 1.2 to 2.0) and with isolated systolic hypertension (relative risk, 1.7; 95% CI, 1.1 to 2.6). We found a continuous increase in stroke incidence with increasing blood pressure in nontreated subjects. In treated subjects, we found a J-shaped relation between blood pressure and the risk of stroke. In the lowest category of diastolic blood pressure, the increase of stroke risk was statistically significant compared with the reference category. Hypertension and isolated systolic hypertension are strong risk factors for stroke in the elderly. The increased stroke risk in the lowest stratum of blood pressure in treated hypertensive patients may indicate that the therapeutic goal of “the lower the better” is not the optimal strategy in the elderly.Key Words: blood pressure, stroke preventionAB-14671-00Warfarin Use Among Ambulatory Patients With Nonvalvular Atrial Fibrillation: The AnTicoagulation and Risk Factors in Atrial Fibrillation (ATRIA) Study—Go AS (Kaiser Permanente Medical Care Program, Div of Research, 3505 Broadway St, 12th Fl, Oakland, CA 94611), Hylek EM, Borowsky LH, Phillips KA, Selby JV, Singer DE—Ann Intern Med. 1999;131:927–934.Background: Warfarin dramatically reduces the risk for ischemic stroke in nonvalvular atrial fibrillation, but its use among ambulatory patients with atrial fibrillation has not been widely studied. Objective: To assess the rates and predictors of warfarin use in ambulatory patients with nonvalvular atrial fibrillation. Design: Cross-sectional study. Setting: Large health maintenance organization. Patients: 13428 patients with a confirmed ambulatory diagnosis of nonvalvular atrial fibrillation and known warfarin status between 1 July 1996 and 31 December 1997. Measurements: Data from automated pharmacy, laboratory, and clinical-administrative databases were used to determine the prevalence and determinants of warfarin use in the 3 months before or after the identified diagnosis of atrial fibrillation. Results: Of 11082 patients with nonvalvular atrial fibrillation and no known contraindications, 55% received warfarin. Warfarin use was substantially lower in patients who were younger than 55 years of age (44.3%) and those who were 85 years of age or older (35.4%). Only 59.3% of patients with one or more risk factors for stroke and no contraindications were receiving warfarin. Among a subset of “ideal” candidates to receive warfarin (persons 65 to 74 years of age who had no contraindications and had previous stroke, hypertension, or both), 62.1% had evidence of warfarin use. Among our entire cohort, the strongest predictors of receiving warfarin were previous stroke (adjusted odds ratio, 2.55 [95% CI, 2.23 to 2.92]), heart failure (odds ratio, 1.63 [CI, 1.51 to 1.77]), previous intracranial hemorrhage (odds ratio, 0.33 [CI, 0.21 to 0.52]), age 85 years or older (odds ratio, 0.35 [CI, 0.31 to 0.40]), and previous gastrointestinal hemorrhage (odds ratio, 0.47 [CI, 0.40 to 0.57]). Conclusions: In a large, contemporary cohort of ambulatory patients with atrial fibrillation who received care within a health maintenance organization, warfarin use was considerably higher than in other reported studies. Although the reasons why physicians did not prescribe warfarin could not be elucidated, many apparently eligible patients with atrial fibrillation and at least one additional risk factor for stroke, especially hypertension, did not receive anticoagulation. Interventions are needed to increase the use of warfarin for stroke prevention among appropriate candidates.Key Words: atrial fibrillation, warfarinExperimental PathologyAB-14672-00Protective Effects of Memantine Against Ischemia-Reperfusion Injury in Spontaneously Hypertensive Rats—Dogan A, Eras MA, Rao VLR, Dempsey RJ (Dept of Neurological Surgery, Univ of Wisconsin, H4/338 Clinical Science Center, 600 Highland Ave, Madison, WI 53792)—Acta Neurochir (Wien). 1999;141:1107–1113. Copyright 1999 © Springer-Verlag.Memantine, an uncompetitive NMDA open-channel blocker, has been shown to be effective in preventing neuronal damage after permanent focal cerebral ischemia. Reperfusion after a long period of ischemia may aggravate the progression of neuronal damage. Those drugs that show protective effects after permanent cerebral ischemia, therefore, might fail to do so against ischemia-reperfusion injury. In this study we evaluated the effects of memantine on brain edema formation and ischemic injury volume after transient cerebral ischemia. Male Spontaneously Hypertensive Rats (SHR) weighing 250–300 g were anesthetized with halothane and subjected to 1 hour of temporary middle cerebral artery occlusion by an intraluminal suture. 20 mg/kg of memantine or saline were injected intraperitoneally 5 min. after the induction of ischemia. Physiological parameters and regional cerebral blood flow were monitored during the surgical procedure. Brain water content and ischemic injury volume were measured with the wet dry method and 2,3,5-triphenyl tetrazolium chloride monohydrate (TTC) staining, respectively, at 24 hours after occlusion. There were no statistically significant differences between the groups regarding physiological parameters during the procedure. Memantine treatment (n=9) reduced the brain water content significantly in the cortex compared to saline treatment (n=8; 83.1±0.7% vs. 84.5±1.5%, respectively, p<0.05). The total volume of ischemic brain injury was 300±49 mm3 in the animals treated with saline (n=13). Treatment with 20 mg/kg memantine (n=14) reduced the ischemic injury volume to 233±61 mm3 (P<0.01). These results demonstrate that the harmful effects of recirculation after a period of ischemia can be attenuated by the treatment of memantine, perhaps by its action at the NMDA receptors.Key Words: cerebral ischemia, N-methyl-d-aspartate AB-14673-00Cerebral Microvascular Obstruction By Fibrin Is Associated With Upregulation of PAI-1 Acutely After Onset of Focal Embolic Ischemia in Rats—Zhang ZG, Chopp M (Henry Ford Hospital, Dept of Neurology, 2799 W Grand Blvd, Detroit, MI 48202), Goussev A, Lu DY, Morris D, Tsang W, Powers C, Ho KL—J Neurosci. 1999;19:10898–10907.The mechanisms underlying cerebral microvascular perfusion deficit resulting from occlusion of the middle cerebral artery (MCA) require elucidation. We, therefore, tested the hypothesis that intravascular fibrin deposition in situ directly obstructs cerebral microcirculation and that local changes in type 1 plasminogen activator inhibitor (PAI-1) gene expression contribute to intravascular fibrin deposition after embolic MCA occlusion. Using laser-scanning confocal microscopy (LSCM) in combination with immunofluorescent staining, we simultaneously measured in three dimensions the distribution of microvascular plasma perfusion deficit and fibrin(ogen) immunoreactivity in a rat model of focal cerebral embolic ischemia (n=12). In addition, using in situ hybridization and immunostaining, we analyzed expression of PAI-1 in ischemic brain (n=13). A significant (p<0.05) reduction of cerebral microvascular plasma perfusion accompanied a significant (p<0.05) increase of intravascular and extravascular fibrin deposition in the ischemic lesion. Microvascular plasma perfusion deficit and fibrin deposition expanded concomitantly from the subcortex to the cortex during 1 and 4 hr of embolic MCA occlusion. Three-dimensional analysis revealed that intravascular fibrin deposition directly blocks microvascular plasma perfusion. Vascular plugs contained erythrocytes, polymorphonuclear leukocytes, and platelets enmeshed in fibrin. In situ hybridization demonstrated induction of PAI-1 mRNA in vascular endothelial cells in the ischemic region at 1 hr of isc