Oral Presentations
2000; Lippincott Williams & Wilkins; Volume: 31; Issue: 1 Linguagem: Inglês
10.1161/01.str.31.1.275
ISSN1524-4628
AutoresBarbara Gregson, A. David Mendelow, AJ Pearson, Haggeas S. Fernandes, HS Siddique,
ResumoHomeStrokeVol. 31, No. 1Oral Presentations Free AccessOtherPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessOtherPDF/EPUBOral Presentations Originally published1 Jan 2000https://doi.org/10.1161/01.STR.31.1.275Stroke. 2000;31:275–346Thursday-Morning1 The Effect of Early and Late Brain Tissue Reperfusion on Infarct VolumeRuediger von Kummer, Univ of Technology, Dresden Germany; Joerg Berrouschot, Barthel Henrik, Hesse Swen, Univ, Leipzig Germany; Christiane Dieler, Univ of Technology, Dresden Germany; Dietmar Schneider, Univ, Leipzig GermanyObjectives: To find out whether brain tissue reperfusion affects the volume of ischemic infarcts if observed within or after 8 hours of stroke onset. Methods: We performed 99mTc-ethyl cysteinate dimer single-photon emission computed tomography (SPECT) in patients included in a single site of the ECASS II before treatment with recombinant tissue plasminogen activator (rt-PA, 0.9 mg/kg IV) (n=26) or placebo (N=26), 6-8 hours after treatment, and after 7±1 days to determine the degree and extent of brain ischemia. Following a prospective protocol, the SPECT scans were analyzed blinded to treatment allocation using a graded scale for quantification. We defined "reperfusion" as a decrease in the graded scale by >25% comparing the follow-up scans with the baseline scan. The infarct volumes were measured using the formula for irregular volumes, blinded to clinical information and the SPECT results. Results: SPECT detected reperfusion in 18 patients within 8 hours and in additional 10 patients at 7 days of stroke onset. Treatment did not affect the frequency of reperfusion. Twenty-four patients did not show reperfusion. These 3 groups did not differ at baseline with regard to gender, age, the NIH Stroke Score, the SPECT graded scale, and the extent of ischemic lesions on CT. One patient with early reperfusion died at day 15 from a non-neurological cause. Eight patients without reperfusion died until day 90, 5 of them from large parenchymal hematoma within 6 days of stroke onset. The mean infarct volume at day 1 was 137 ± 141 ml without reperfusion, 37 ± 30 ml with late reperfusion (p=0.01, vs. no reperfusion), and 21± 26 ml with early reperfusion (p=0.0005, vs. no reperfusion). The mean infarct volume at day 7 was 115 ± 139 ml without reperfusion, 56 ± 42 ml with late reperfusion, and 26± 33 ml with early reperfusion (p=0.0067 vs. no reperfusion). Patients with early and late reperfusion had a better clinical outcome at 90 days than patients without reperfusion. Conclusion: Spontaneous reperfusion even if delayed 8 hours after stroke onset was associated with smaller infarctions and better clinical outcome.2 The Validity and Reliability of a Novel Quantitative CT Score in Predicting Outcome Prior to Thrombolytic TreatmentPhilip A Barber, Andrew M Demchuk, Jinjin Zhang, Univ of Calgary, Calgary, AB Canada; Robert Sevick, William Hu, Mark Hudon, James Scott, Deepak Kaura, Foothills Hosp, Calgary, AB Canada; Alastair M Buchan, Univ of Calgary, Calgary, AB CanadaBackground The significance of early ischemic change in the context of hyperacute stroke is unclear. Concern exists over the ability of clinicians to correctly recognise and interpret these changes. Improved methods of recognising and quantifying early CT changes are needed to influence patient selection for thrombolytic therapy. Methods Consecutive patients with anterior circulation ischemic stroke were treated with intravenous t-PA according to NINDS guidelines. All pretreatment CT scans were prospectively evaluated blind to clinical information by 2 methods of quantifying middle cerebral artery territory (MCA) early CT change: (1) a novel 10 point CT score (Alberta Stroke Program Early CT Score, ASPECTS); and (2) the less than/ greater than 1/3 MCA territory rule. Primary outcome measures evaluated included symptomatic intracerebral hemorrhage, and 3 month Rankin score. Factors that predict functional outcome and symptomatic intracerebral hemorrhage were identified by logistic regression. The inter-observer reliability of the two methods were assessed between stroke neurologists, radiology trainees, and experienced neuroradiologists. Results A total of 156 patients were included in the analysis. Logistic regression identified that ASPECTS predicts functional outcome and symptomatic hemorrhage, controlling for the simultaneous effects of age, stroke severity, and serum glucose (p<0.01 respectively). An ASPECTS score of 7 and below has a sensitivity of 0.78, specificity 0.96 compared to a sensitivity of 0.73 and a specificity 0.91 for the 1/3 MCA territory rule. The measure of agreement between observers was very good for the ASPECTS (Kappa 0.7-0.76) and fair to moderate for the MCA territory rule (Kappa 0.4-0.55). The intra- rater reliability for each clinician ranged from k 0.67-0.84 for ASPECTS and k 0.26-0.76 for the MCA rule. Conclusion The ASPECTS scoring system is a practical method that predicts functional outcome and of symptomatic hemorrhage in stroke patients treated with t-PA. This system appears to have improved intra and inter-observer reliability compared to the less than/ greater than 1/3 MCA rule.3 Acute Cerebral Blood Flow as a Predictive Physiologic Marker for Symptomatic Hemorrhagic Conversion and Clinical Herniation After Thrombolytic TherapySteven Goldstein, Howard Yonas, James M Gebel, Amin Kassam, Charles A Jungreis, Guven Uzun, Andrew D Firlik, Giorgio Rubin, Lawrence R Wechsler, Univ of Pittsburgh Med Ctr Stroke Institute, Pittsburgh, PABackground and Purpose: We looked at the ability of quantitative cerebral blood flow (qCBF) to act as a physiologic marker for the identification of patients (pts.) at high risk for symptomatic hemorrhagic conversion (SHC) and/or clinical herniation (CH). Methods: We reviewed 32 pts. with acute cerebral infarction and who had qCBF measurements prior to or concomitant with thrombolytic therapy. Treatment was administered as follows: intravenous (iv) t-PA in accordance with FDA approved clinical guidelines (N=14), intra-arterial (ia) urokinase (UK) (N=7), ia UK and angioplasty (N=4), combined iv t-PA (0.6 mg/kg) and ia t-PA (0.3 mg/kg) including one with concomitant angioplasty (N=5), iv t-PA and ia UK (N=1) and ia t-PA (N=1). All pts. receiving iv t-PA , iv/ia t-PA or iv t-PA and ia UK were treated within 3 hours and pts. treated with ia UK or ia t-PA were treated within 6 hours of stroke onset. qCBF measurements were performed using xenon enhanced computerized tomography (XeCT). The mean qCBF in the symptomatic vascular territory was calculated by averaging standard regions of interest (ROI) in 3-4 hemispheric brain levels. Focal qCBF was defined as two adjacent ROI within the symptomatic vascular territory with the lowest qCBF averaged over 3-4 hemispheric levels. Non-contrast CT scans were performed prior to and 24-72 hours after treatment. Results: The mean qCBF in pts. with SHC and/or CH after thrombolysis ( N=9) was 14.3 ml/100gr/min. In pts. without SHC or CH after thrombolysis (N=23) the mean qCBF was 28.8 ml/100gr/min. P<0.0002. The focal qCBF in pts. with SHC and/or CH after thrombolysis was 8.6 ml/100gr/min. In pts. without SHC or CH after thrombolysis the focal qCBF was 20.3 ml/100gr/min. P<0.0007. Conclusions: XeCT qCBF can be combined with CT equipment, providing qCBF information for review within 15 minutes. It is ideally suited as a diagnostic study in pts. with acute stroke. qCBF may be an effective physiologic marker for the identification of patients at high risk for SHC and/or CH after thrombolytic therapy. By improving patient selection the utilization of thrombolytic therapy may be increased.4 Thrombolysis in Brain Ischemia (TIBI) Flow Grades Predict Likelihood of Recanalization and Recovery in Intravenous TPA Treated PatientsAndrew M Demchuk, Ioannis Christou, Robert A Felberg, Univ of Texas, Houston, Houston, TX; Philip A Barber, Univ of Calgary, Calgary, AB Canada; Marc Malkoff, Andrei V Alexandrov, Univ of Texas, Houston, Houston, TXBackground: Residual flow surrounding occlusion is an important predictor for success with coronary thrombolysis. Thrombolysis in Myocardial Ischemia (TIMI) grading system is an angiographic classification to measure residual flow and recanalization. We developed a Thrombolysis in Brain Ischemia (TIBI) classification using transcranial Doppler (TCD) to noninvasively monitor residual flow signals. In this study we examine the relationship between stroke severity and outcome in intravenous TPA patients evaluated by TCD emergently using this new TIBI classification. Methods: Previously established TCD occlusion criteria were followed to determine site of arterial occlusion. Residual flow waveforms were identified by TCD at depth just distal to presumed occlusion site, before, during and after intravenous (IV) TPA treatment. TIBI Grade I consisted of absent and minimal waveforms; Grade II: blunted and dampened; Grade III: stenotic and normal. NIHSS scores were obtained at baseline and discharge. Results: 62 IV TPA treated patients were studied prospectively (age 66±16 years, pre-TPA NIHSS 16.4±6.2, TPA bolus at 139±58 min); 7 patients were excluded from the analysis (5 no temporal windows, 2 missing data). Pre-TPA NIHSS scores were 19.5±6.0 for Grade I, n=30; 13.5±4.6 for Grade II, n=15; and 12.2±5.9 for Grade III, n=10 (p<0.05, I vs III). TIBI flow improvement to Grade III occurred in 30% (9/30) of initial Grade I and 46% (7/15) of initial Grade II patients. Patients with final Grade III had follow-up NIHSS 6.2±9.8 (n=17), final Grade II 12.7±9.7 (n=13), and final Grade I 21±11 (n=11), (p= 0.05, I vs II and III). In-hospital mortality was 35% (11/30) in patients with pre-TPA Grade I flow, and 12% (3/25) in pre-TPA Grades II-III, (χ2=4.37 p= 0.037). Conclusions: No or minimal residual flow (TIBI Grade I) correlates with severe pretreatment neurologic deficit, poor clinical recovery and higher mortality in IV TPA treated patients. The presence of residual flow (Grades II and III) before thrombolysis is a prognostically favorable sign. The degree of TIBI flow grade improvement correlates with short-term recovery.5 Post-Approval Experience of Intracerebral Hemorrhage Following Intravenous T-PA Therapy for Acute Ischemic Stroke: CT Risk FactorsWayne M Clark, Oregon Stroke Ctr, Portland, OR; Gregory W Albers, Stanford Univ, Palo Alto, CA; Scott A Hamilton, For the STARS Study Investigators, Genentech, Inc, San FranciscoOBJECTIVE: To identify variables predictive of intracerebral hemorrhage in patients treated with intravenous t-PA for acute ischemic stroke in routine clinical practice. Data were collected as part of the Standard Treatment with Activase to Reverse Stroke (STARS) project which was a prospective, monitored, multi-center study evaluating the post-approval experience with t-PA. METHODS:391 patients who were treated for stroke with intravenous t-PA at 59 centers were enrolled in this study. Data regarding baseline characteristics, medications, medical history, and CT-scan results were collected. Data on symptomatic and asymptomatic intracerebral hemorrhage were collected during the initial hospitalization and at 30 days. Using multivariable regression, the relationship of the baseline variables with symptomatic and asymptomatic hemorrhage during the first 72 hours was assessed. RESULTS: A total of 41 patients (11%) experienced an ICH during the first 72 hours following treatment. Thirteen (3%) of the patients experienced a symptomatic hemorrhage and 28 (7%) experienced an asymptomatic hemorrhage. Of the 81 patients with evidence of stroke on the baseline CT scan, five (6%) experienced a symptomatic ICH compared to 8/308 (2.5%) without evidence, p=0.15. Of the ten patients with effacement and/or hypodensity in greater than a third of the MCA territory, 2 (20%) experienced a symptomatic ICH (2.9% without), p=0.04. Twenty-three patients had edema and three (13%) experienced a symptomatic ICH (2.7% without), p=0.035. Of the seven patients with mass effect, 2 (30%) had a symptomatic ICH (2.9% without), p=0.02. Baseline and follow-up CT scans will be presented. A multivariate analysis including CT and clinical variables is in progress. CONCLUSIONS: In this consecutive study of acute stroke patients treated with t-PA the reported rates of ICH were lower, but comparable to the NIH t-PA study. Univariate, unadjusted predictors of symptomatic ICH were effacement and hypodensity in greater than a third of the MCA territory, edema, and mass effect. Results of the multivariable model will be presented.6 Relationship Between Diffusion and Perfusion Weighted MRI Findings and Hemorrhagic Transformation Following Acute Ischemic Stroke: Preliminary ObservationsDavid C Tong, Stanford Stroke Ctr, Palo Alto, CA; Alessandro Adami, Univ di Verona, Verona Italy; MIchael P Marks, Michael E Moseley, Stanford Univ, Stanford, CABackground and Purpose: Little is known about the relationship between diffusion and perfusion weighted MRI findings and the risk of secondary hemorrhage following acute ischemic stroke. This information could be of potentially great value, particularly in patients being considered for thrombolytic or anticoagulant therapy. Methods: We retrospectively reviewed all acute stroke patients that were evaluated with DWI or PWI within 8 hours of symptom onset and that received also a follow up MRI (n=24) or CT scan (n=3). We studied the relationship between initial DWI/PWI findings and subsequent hemorrhage in these patients. Results: 27 patients were identified. 16 patients received rt-PA and 11 did not. Overall, hemorrhage was detected in 16/27 (60%), and was symptomatic in 11% (n=3). The FLAIR apparent diffusion coefficient (ADCFL) of the ischemic areas that subsequently developed hemorrhage (ADCFLHEM) were significantly lower than the ischemic lesions as a whole (ADCFLAVG)[0.484 ± 0.170 x 10-5 cm2/s, versus 0.621 ± 0.123 x10-5 cm2/s, p=0.002]. An early (<36 h) ADC rise was also identified in 10/13 (77%) patients experiencing hemorrhagic transformation compared with 2/8 (25%) patients not experiencing hemorrhagic change (p=0.03). In addition, low perfusion was identified acutely in 91% (10/11) patients who had PWI performed initially and experienced subsequent HT compared with 0/7 (0%) patients with no subsequent HT (p<0.001). There was no relationship between time to PWI resolution and subsequent hemorrhage. Conclusions: Both DWI and PWI can identify abnormalities that are associated with subsequent hemorrhagic change. These findings may be helpful in identifying patients who are at increased risk for bleeding complications following acute stroke.7 Early CT Changes and Outcome of Ischemic StrokeNatan M Bornstein, Boris D Aronovich, Irith I Reider-Groswasser, Joram Segev, Sourasky Med Ctr, Tel Aviv IsraelBackground: Although recombinant tissue plasminogen activator (rtPA) was implemented as part of the emergency care of acute stroke, its use in daily clinical practice still remains controversial in many countries. The most important question for the clinician is what should be the criteria for careful selection of certain subgroup of patients for this treatment. Objective:The aim of our study was to estimate the correlation between early CT findings and outcome of patients with acute stroke. Methods and results: We conducted a prospective outcome study of patients with acute ischemic stroke (IS) admitted to hospital within 6 hours of symptom onset. All CT scans carried out in the emergency room were read by experienced neuroradiologists blind to the clinical outcome of the patients. Early CT changes were defined as in ECASS 2. In addition to these parameters, we also analyzed tissue characteristics of the brain which was unaffected by acute stroke. Our approach included the assessment of tissue loss (according to the width of the 3rd ventricle, 3VW) and alteration in the tissue characteristics (gray-white matter distribution, GWMD, and leukoaraiosis, LA). 150 consecutive patients (75 males, mean age 72.5±9.0 ) with IS (54.7 % mild strokes and 45.3 % severe strokes) were evaluated. Early CT changes were: hypodensity 55.7 %, effacement of sulci 41.3 %, hyperdensity of MCA 13.3%, hypodensity of lentiform 20.7 %, loss of Ribbon sign 28.7 %. The correlation between early CT changes and outcome (discharge, rehabilitation, chronic care, and death) were analyzed by Pearson s X2. No significant correlation was found between ECASS2 early CT changes and outcome even after adjustment for other vascular risk factors. Quantitative analysis of the characteristics that we added revealed a tendency toward better prognosis (fewer deaths, p=0.008) in patients with worse GWMD and poorer prognosis (more deaths, p=0.08) in patients with LA. Conclusion: Although early signs on the CT scan are common in the first 6 hours from stroke onset, we found no correlation with clinical outcome. The existing correlation between tissue characteristics and outcome which emerged will be discussed.8 Identification of Targets for Therapy by H2O/FMZ-PET in Early StrokeWolf-Dieter Heiss, Lutz Kracht, Alexander Thiel, Martin Grond, Jobst Rudolf, Rudolf Graf, MPI f neurol Forschung, Cologne GermanyObjective: To differentiate irreversibly damaged from viable penumbra tissue in the first hours after ischemic stroke by multitracer PET-studies. Background: Central benzodiazepine receptor ligands, as 11C-flumazenil (FMZ), are markers of neuronal integrity and can identify morphologically damaged neurons. Sub-threshold flow assessed by H215O-PET indicates critically perfused tissue. Methods: In 10 patients (7 male, 3 female, 52-76 years) FMZ and H215O-PET studies were performed 2-12 h after onset of acute ischemic hemispheric stroke. Cortical areas of decreased FMZ binding and areas of reduced flow ("critical": < 50%, "penumbra": 50-70% of contralateral mean) were identified and related to the extent of morphologic damage on MRT or CT 2-3 weeks after stroke. Results: In all patients cortical infarcts were found at the final CT/MRI, but size varied ,(0.7-150.0, mean 30.8 cm3). A large portion (21.1 cm3 or 68%) was identified in early PET studies by reduction of FMZ binding and critically reduced CBF. Penumbra (1.6%) or normal flow (< 1%) together with reduced FMZ contributed only marginally to the final infarct. In 24.9% of the final infarct FMZ was not decreased at the initial study. Flow was reduced below the critical value (6.0 cm3 = 9.5%) or to penumbra values (1.7 cm3 = 5.4%). Areas of normal flow and FMZ contributed to 4.2% of the final infarct. One patient's small volume (> 1 cm3) with reduced FMZ was not included in the final small infarct (0.7 cm3), possibly due to partial volume effects impairing comparability of different techniques in small lesions. Conclusions: These results demonstrate that irreversibly damaged tissue can be distinguished early after acute stroke from the critically perfused but viable "penumbra" compartment which could benefit from (reperfusion) therapy (in this study 25% of the final infarcts). In a small compartment (5%), however, critical hypoperfusion was not evident suggesting secondary ischemic damage.9 Do Early CT Changes Predict Clinical Outcome Following Administration of Intravenous R-Tpa for Acute Ischemic Stroke?Douglas N Lurie, Jorge E Mendizabal, Francis G Greiner, Richard M Zweifler, Univ of South Alabama, Mobile, ALBackground: Intravenous (IV) recombinant tissue plasminogen activator (r-tPA) is currently the only therapy of proven value for patients with acute ischemic stroke (AIS). There are conflicting data regarding the prognostic value of early CT changes in patients who receive r-tPA for AIS and few data speak to the prognostic value of these signs when rt-PA is administered as per the NINDS protocol (i.e., within 3 hours of stroke onset). The presence of early CT changes may predict a poor clinical response to IV rt-PA. Methods: Forty patients received IV rt-PA for AIS at a University of South Alabama HospitalbetweenJanuary 1996 and May 1999. A board-certified neuroradiologist, blinded to clinical outcomes, reviewed initial CT scans for the presence of the following: hyperdense middle cerebral artery (HMCA), loss of gray-white differentiation (LGWD), insular ribbon sign (IRS), parenchymal hypodensity (PH), sulcal effacement (SE) and intraparenchymal hemorrhage (IH). A modified Rankin scale (mRS) was prospectively obtained 90 days post-stroke and the score was dichotomized to represent favorable (0-1) or unfavorable (2-6) outcomes. The relationship between presence of early CT scan signs and 90-day mRS scores was evaluated using Chi-square analysis with Bonferroni correction for multiple comparisons. Results:During the study period, 40 patients received rt-PA. Complete data were available for 36 patients. The median admission NIH Stroke Scale score was 13, median admission mRS was 4, and median 90-day mRS was 2. Early CT changes were detected in 23 (64%) patients. Early changes encountered include HMCA in 4 cases (11%), LGWD in 12 (33%), IRS in 3 (8%), PH in 9 (25%), SE in 13 (36%). We found no statistically significant difference between the occurrence of these imaging findings and the functional outcome at 90 days post-thrombolysis. Conclusions: Our data suggest that the presence of early CT findings in patients with AIS does not predict unfavorable outcome following IV thrombolysis with rt-PA.10 Subarachnoid Hemolysate Produces Cytochrome C Translocation into Cytosol in Mouse NeocortexPaul G Matz, Miki Fujimura, Yuiko Morita-Fujimura, Pak H Chan, Stanford Univ, Palo Alto, CAObjective: Prior to apoptosis, cytochrome c translocation in brain has been observed after ischemic and traumatic oxidative injury in vivo. Since hemolysate exposure has recently been associated with oxidative stress and apoptosis in vivo, we hypothesized that it would also produce cytochrome c translocation in brain. Methods: Subarachnoid hemorrhage (SAH) was induced in CD-1 mice (male, 3 months, n=22) by subarachnoid injection of autologous hemolysate (50μL) over the neocortex. Saline-injected mice (n=18, 50μL saline) were used for controls. Subjects were sacrificed at 2h, 4h, and 24h after SAH or saline injection by transcardiac perfusion-fixation (n=6 for each time point with n=6 controls). Serial sections were immunostained for cytochrome c using a rabbit polyclonal antibody. In a second group, mice were sacrificed at 4h (n=2) and 24h (n=2) after SAH. Fresh neocortex was removed ipsilateral and contralateral to the SAH. Cytosolic cell fractions were isolated by ultracentrifugation. Western blot analysis for cytochrome c was performed on the cytosolic fractions of ipsilateral and contralateral neocortex. Results: After SAH, cytosolic cytochrome c was evident on immunostaining at 2h (5/6, Fisher exact p<0.02) in regions closest to the SAH. Cytochrome c immunoreactivity continued to be observed at 4h and 24h after SAH (5/6 subjects in each group, Fisher exact p<0.02). Saline injection did not produce cytochrome c immunoreactivity (0/6 in all groups) confirming that mitochondrial cytochrome c alone does not produce immunoreactivity. Western blot analysis demonstrated cytochrome c at 4h and 24h in the cytosolic fraction of neocortex ipsilateral to the SAH. The cytosolic component of contralateral neocortex did not immunoblot for cytochrome c at 4h and 24h. Conclusion: Subarachnoid hemolysate exposure in neocortex is associated with cytochrome c translocation from mitochondria to cytosol. This mechanism may play a role in cell injury after SAH and may predispose underlying neocortex to apoptotic cell death after SAH.11 Some Potentially Harmful Side Effects of Anti-ICAM-1 Antibody Administration in Preclinical Animal Studies of StrokeKazuhide Furuya, Hidetaka Takeda, Salman Azhar, Thomas J DeGraba, National Institute of Neurological Disorders and Stroke, Bethesda, MD; Robert Rothlein, Boehringer Ingelheim Pharmaceuticals, Inc, Ridgefield, CT; Tony E Hugli, Gregory J del Zoppo, The Scripps Res Institute, La Jolla, CA; John M Hallenbeck, National Institute of Neurological Disorders and Stroke, Bethesda, MDA clinical trial of murine anti-human ICAM-1 antibody (Enlimomab) therapy of acute stroke produced a higher incidence of clinical deterioration in treated than in control patients. Evidence that monoclonal anti-ICAM-1 antibody (1A29) can activate expression of E-selectin and/or P-selectin on brain microvessels has been reported. We report additional evidence of the harmful side effects of 1A29 in preclinical animal models of stroke. Wistar rats and SHRs were subjected to permanent middle cerebral artery occlusion (MCAO) with 2 h (Wistar) or 1 h (SHR) occlusion of the ipsilateral common carotid artery (CCAO) as partial focal reperfusion models. 1A29 (2 mg/kg), PBS or isotype-matched immunoglobulin (IgG1) were administered intravenously just after reopening of the CCAO and 24 h after MCAO. The infarct volume was assessed at 48 h after MCAO. 1A29 treatment did not cause a statistically significant decrease of the infarct size in either strain compared to PBS and IgG1-treated animals [Wistar 1A29: 106±36 (Mean±SD,mm3), Wistar PBS: 135.2±27.4, Wistar IgG1: 117.8±39.8, SHR 1A29: 151.9±18.4, SHR PBS: 149±8.8, SHR IgG1: 149.8±23.3]. We sensitized Wistar rats with 1A29 (200 μg/kg i.p.)or PBS as a control at 7 days prior to surgery, followed by 1A29 treatment after surgery. 1A29-sensitized rats showed a statistically significant exacerbation of infarct volume (159±29) compared to controls (122±12). Although 1A29 inhibited leukocyte accumulation as shown by reduction in brain myeloperoxidase activity, circulating leukocytes were activated as demonstrated by flowcytometer mean fluorescence intensity of CD11b/18 expression on neutrophils 48 h after MCAO (Wistar 1A29: 11.6±2.0, Wistar PBS: 5.8±0.9, SHR 1A29: 9.5±2.5, SHR PBS: 6.3±1.6). 1A29 also caused significant granulocytosis in both strains and 1A29-treated SHRs significantly lost weight during 48 h. Potential mechanisms include generation of rat anti-murine antibody, complement fixation and acute cytokine response. These data bear on the mechanisms of clinical deterioration that occurred in the Enlimomab trial.12 Intracerebral Transplantation of Bone Marrow- Derived Mesenchymal Cells After Stroke in Adult MiceYi Li, Jieli Chen, Lei Wang, Dexian Dou, Michael Chopp, Henry Ford Hosp, Detroit, MIWe transplanted adult mesenchymal stem and progenitor cells (MSCs) into the striatum of the adult mouse brain after embolic middle cerebral artery occlusion (MCAo). Mice (n=28) were divided into five groups. Experimental mice were subjected to MCAo and transplanted with a. conventional cultured MSCs (n=5) and b. MSCs cultured with a neuronal growth factor (NGF, n=5). Control mice were subjected to c. MCAo alone (n=8); d. injection of phosphate buffered saline (PBS) into the ischemic striatum (n=5); and e. transplantation of MSCs into the normal striatum (n=5). Donor cells were harvested from mice injected with bromodeoxyuridine (BrdU, as a tracer) and were transplanted into the ischemic striatum at 4 d after MCAo. All mice were sacrificed at 28 d after the ischemic onset. Using single and double immunohistochemistry methods, we identified the phenotypic fate of donor cells and ischemic damaged brain tissue. Behavioral tests for modified neurological severity score (NSS) and a Rotarod were scored in mice. Compared with controls, our data indicate that BrdU positive MSCs were present and migrated a distance (∼1.7 mm) from the grafting area toward the ischemic striatum, corpus callosum and cortex at 28 d after MCAo in both experimental groups a and b. BrdU positive cells expressed neuronal (∼2%, NeuN; ∼10%, TH; ∼8% GABA) or astrocytic (∼3%, GFAP) phenotypes. NGF treatment increased the survival (∼10 x) of donor cells in vivo. No difference in the ischemic volume at 28 d was detected among MCAo alone and transplanted MSCs with or without NGF. Mice receiving MSCs with NGF exhibited significant recovery from the modified NSS (p<0.05) and rotarod test (p<0.05) compared with MCAo alone. Our findings suggest that the transplantation of adult MSCs cultured with NGF improves MSCs survival in ischemic brain and behavioral recovery from asymmetric brain damage in adult mice. The MSC population can be easily isolated from the bone marrow of humans and other species and expanded in culture (in the absence of differentiation) by a factor of at least 105 (18 doublings). MSCs may provide a new avenue to induce plasticity in injured brain.13 Proliferation and Differentiation of Ependymal and Choroidal Cells After Stroke in RodentsYi Li, Jieli Chen, Michael Chopp, Henry Ford Hosp, Detroit, MIRecent data suggest that the inner surface of the adult brain is lined with ependymal cell that have the power of differentiation. Choroidal cells are modified ependymal cells. To identify and characterize neural stem cells response to middle cerebral artery occlusion in rats (n=28) and mice (n=28), animals were sacrificed at 1, 2, 4, 7, 14, 21 & 28 d (n=4, per time point)after stroke, respectively. We employed antibodies against intermediate filament proteins (nestin, vimentin, glial fibrillary acidic protein - GFAP, neurofilament proteins - NF), proliferation cellular nuclear antigen (PCNA), bromodeoxyurodine (BrdU), neuronal nuclear antigen (NeuN) and microtubule associate protein 2 (MAP-2) in single and double immunostaining. Focusing on morphological approaches, we observed that a. in normal non ischemic rats and mice (n=4, respectively), most ependymal cells and scattered choroid cells express nestin, vimentin, PCNA and BrdU; b.however, after stroke, ependymal cells in the ventricular zone and cells derived from subventricul
Referência(s)