The Experts below are selected from a list of 2721 Experts worldwide ranked by ideXlab platform
Lawrence L Latour - One of the best experts on this subject based on the ideXlab platform.
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evidence of reperfusion injury exacerbated by thrombolytic therapy in human Focal Brain Ischemia using a novel imaging marker of early blood Brain barrier disruption
Stroke, 2004Co-Authors: Steven Warach, Lawrence L LatourAbstract:Loss of integrity of the blood–Brain barrier (BBB) resulting from Ischemia and reperfusion is a hypothesized precursor to hemorrhagic transformation (HT) and worse clinical outcome than would be expected from the beneficial effects of reperfusion. We used a novel magnetic resonance imaging marker to characterize early BBB disruption in acute Focal Brain Ischemia and tested associations with reperfusion, HT, and poor outcome (modified Rankin score >2). The BBB disruption was evident as delayed gadolinium enhancement of cerebrospinal fluid space on fluid-attenuated inversion recovery (FLAIR) images and, for convenience, has been termed hyperintense acute reperfusion marker (HARM). HARM was found in 47 of 144 (33%) ischemic stroke patients. Reperfusion was found to be the strongest independent predictor of early BBB disruption ( P =0.018) in multivariate analysis. HARM was associated with HT and worse clinical outcome (after adjustment for initial severity). It was also associated with more severe strokes at onset and greater age. Because the timing of the disruption was early enough (median estimate 3.8 hours from onset) to make it relevant to acute thrombolytic therapy, early BBB disruption as defined by HARM may be a promising target for adjunctive therapy to reduce the complications associated with thrombolytic therapy, broaden the therapeutic window, and improve clinical outcome.
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early blood Brain barrier disruption in human Focal Brain Ischemia
Annals of Neurology, 2004Co-Authors: Lawrence L Latour, Dongwha Kang, Mustapha A Ezzeddine, Julio A Chalela, Steven WarachAbstract:Loss of integrity of the blood–Brain barrier (BBB) resulting from Ischemia/reperfusion is believed to be a precursor to hemorrhagic transformation (HT) and poor outcome. We used a novel magnetic resonance imaging marker to characterize early BBB disruption in human Focal Brain Ischemia and tested for associations with reperfusion, HT, and poor outcome (modified Rankin score >2). BBB disruption was found in 47 of 144 (33%) patients, having a median time from stroke onset to observation of 10.1 hours. Reperfusion was found to be the most powerful independent predictor of early BBB disruption (p = 0.018; odds ratio, 4.09; 95% confidence interval, 1.28–13.1). HT was observed in 22 patients; 16 (72.7%) of those also had early BBB disruption (p 6), early BBB disruption was found to be an independent predictor of HT. Because the timing of the disruption was early enough to make it relevant to acute thrombolytic therapy, early BBB disruption as defined by this imaging biomarker may be a promising target for adjunctive therapy to reduce the complications associated with thrombolytic therapy, broaden the therapeutic window, and improve clinical outcome. Ann Neurol 2004
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Early blood–Brain barrier disruption in human Focal Brain Ischemia
Annals of Neurology, 2004Co-Authors: Lawrence L Latour, Dongwha Kang, Mustapha A Ezzeddine, Julio A Chalela, Steven WarachAbstract:Loss of integrity of the blood–Brain barrier (BBB) resulting from Ischemia/reperfusion is believed to be a precursor to hemorrhagic transformation (HT) and poor outcome. We used a novel magnetic resonance imaging marker to characterize early BBB disruption in human Focal Brain Ischemia and tested for associations with reperfusion, HT, and poor outcome (modified Rankin score >2). BBB disruption was found in 47 of 144 (33%) patients, having a median time from stroke onset to observation of 10.1 hours. Reperfusion was found to be the most powerful independent predictor of early BBB disruption (p = 0.018; odds ratio, 4.09; 95% confidence interval, 1.28–13.1). HT was observed in 22 patients; 16 (72.7%) of those also had early BBB disruption (p 6), early BBB disruption was found to be an independent predictor of HT. Because the timing of the disruption was early enough to make it relevant to acute thrombolytic therapy, early BBB disruption as defined by this imaging biomarker may be a promising target for adjunctive therapy to reduce the complications associated with thrombolytic therapy, broaden the therapeutic window, and improve clinical outcome. Ann Neurol 2004
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mri diffusion mapping of reversible and irreversible ischemic injury in Focal Brain Ischemia
Neurology, 1994Co-Authors: Yasuhiro Hasegawa, Lawrence L Latour, Marc Fisher, Bernard J Dardzinski, Christopher H SotakAbstract:The reduction of the apparent diffusion coefficient (ADC) of water shortly after a Focal ischemic insult is thought to reflect intracellular water accumulation (cytotoxic edema) related to high-energy metabolism failure and loss of ion homeostasis. We attempted to clarify whether varying ranges of ADC measurements in ischemic Brain tissue can be used to differentiate between reversible and irreversible ischemic lesions before reperfusion in a temporary Ischemia model. We induced 45 minutes of temporary Ischemia in 12 rats using the middle cerebral artery suture occlusion method. Regional changes of ADC values were serially measured in seven regions of interest in each hemisphere and evaluated by ΔADC, defined as the difference between ADC value in an ischemic region and that in a contralateral homologous region. We acquired dynamic contrast-enhanced perfusion images 2 minutes before and after reperfusion to document reduced perfusion and its restoration. We confirmed the infarct area by 2,3,5-triphenyltetrazolium chloride staining 24 hours after occlusion and correlated this with the MRI studies. Recovery of initially reduced ADC values occurred only in ischemic regions where ΔADC values were not below −0.25 × 10 −5 cm 2 /sec. Although the extent of infarction at postmortem examination varied in regions with moderately decreased prereperfusion ADC values, more than 70% of regions of interest with slight declines of prereperfusion ADC values exhibited no infarction. ADC values progressively decreased after reperfusion in regions that initially had severely decreased prereperfusion ADC values, and postmortem examination always demonstrated infarction in such regions. These results suggest that measurement of ΔADC can provide information that will enable the clinician to discriminate between irreversible and potentially reversible ischemic regions before reperfusion is performed.
Steven Warach - One of the best experts on this subject based on the ideXlab platform.
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evidence of reperfusion injury exacerbated by thrombolytic therapy in human Focal Brain Ischemia using a novel imaging marker of early blood Brain barrier disruption
Stroke, 2004Co-Authors: Steven Warach, Lawrence L LatourAbstract:Loss of integrity of the blood–Brain barrier (BBB) resulting from Ischemia and reperfusion is a hypothesized precursor to hemorrhagic transformation (HT) and worse clinical outcome than would be expected from the beneficial effects of reperfusion. We used a novel magnetic resonance imaging marker to characterize early BBB disruption in acute Focal Brain Ischemia and tested associations with reperfusion, HT, and poor outcome (modified Rankin score >2). The BBB disruption was evident as delayed gadolinium enhancement of cerebrospinal fluid space on fluid-attenuated inversion recovery (FLAIR) images and, for convenience, has been termed hyperintense acute reperfusion marker (HARM). HARM was found in 47 of 144 (33%) ischemic stroke patients. Reperfusion was found to be the strongest independent predictor of early BBB disruption ( P =0.018) in multivariate analysis. HARM was associated with HT and worse clinical outcome (after adjustment for initial severity). It was also associated with more severe strokes at onset and greater age. Because the timing of the disruption was early enough (median estimate 3.8 hours from onset) to make it relevant to acute thrombolytic therapy, early BBB disruption as defined by HARM may be a promising target for adjunctive therapy to reduce the complications associated with thrombolytic therapy, broaden the therapeutic window, and improve clinical outcome.
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early blood Brain barrier disruption in human Focal Brain Ischemia
Annals of Neurology, 2004Co-Authors: Lawrence L Latour, Dongwha Kang, Mustapha A Ezzeddine, Julio A Chalela, Steven WarachAbstract:Loss of integrity of the blood–Brain barrier (BBB) resulting from Ischemia/reperfusion is believed to be a precursor to hemorrhagic transformation (HT) and poor outcome. We used a novel magnetic resonance imaging marker to characterize early BBB disruption in human Focal Brain Ischemia and tested for associations with reperfusion, HT, and poor outcome (modified Rankin score >2). BBB disruption was found in 47 of 144 (33%) patients, having a median time from stroke onset to observation of 10.1 hours. Reperfusion was found to be the most powerful independent predictor of early BBB disruption (p = 0.018; odds ratio, 4.09; 95% confidence interval, 1.28–13.1). HT was observed in 22 patients; 16 (72.7%) of those also had early BBB disruption (p 6), early BBB disruption was found to be an independent predictor of HT. Because the timing of the disruption was early enough to make it relevant to acute thrombolytic therapy, early BBB disruption as defined by this imaging biomarker may be a promising target for adjunctive therapy to reduce the complications associated with thrombolytic therapy, broaden the therapeutic window, and improve clinical outcome. Ann Neurol 2004
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Early blood–Brain barrier disruption in human Focal Brain Ischemia
Annals of Neurology, 2004Co-Authors: Lawrence L Latour, Dongwha Kang, Mustapha A Ezzeddine, Julio A Chalela, Steven WarachAbstract:Loss of integrity of the blood–Brain barrier (BBB) resulting from Ischemia/reperfusion is believed to be a precursor to hemorrhagic transformation (HT) and poor outcome. We used a novel magnetic resonance imaging marker to characterize early BBB disruption in human Focal Brain Ischemia and tested for associations with reperfusion, HT, and poor outcome (modified Rankin score >2). BBB disruption was found in 47 of 144 (33%) patients, having a median time from stroke onset to observation of 10.1 hours. Reperfusion was found to be the most powerful independent predictor of early BBB disruption (p = 0.018; odds ratio, 4.09; 95% confidence interval, 1.28–13.1). HT was observed in 22 patients; 16 (72.7%) of those also had early BBB disruption (p 6), early BBB disruption was found to be an independent predictor of HT. Because the timing of the disruption was early enough to make it relevant to acute thrombolytic therapy, early BBB disruption as defined by this imaging biomarker may be a promising target for adjunctive therapy to reduce the complications associated with thrombolytic therapy, broaden the therapeutic window, and improve clinical outcome. Ann Neurol 2004
Mustapha A Ezzeddine - One of the best experts on this subject based on the ideXlab platform.
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early blood Brain barrier disruption in human Focal Brain Ischemia
Annals of Neurology, 2004Co-Authors: Lawrence L Latour, Dongwha Kang, Mustapha A Ezzeddine, Julio A Chalela, Steven WarachAbstract:Loss of integrity of the blood–Brain barrier (BBB) resulting from Ischemia/reperfusion is believed to be a precursor to hemorrhagic transformation (HT) and poor outcome. We used a novel magnetic resonance imaging marker to characterize early BBB disruption in human Focal Brain Ischemia and tested for associations with reperfusion, HT, and poor outcome (modified Rankin score >2). BBB disruption was found in 47 of 144 (33%) patients, having a median time from stroke onset to observation of 10.1 hours. Reperfusion was found to be the most powerful independent predictor of early BBB disruption (p = 0.018; odds ratio, 4.09; 95% confidence interval, 1.28–13.1). HT was observed in 22 patients; 16 (72.7%) of those also had early BBB disruption (p 6), early BBB disruption was found to be an independent predictor of HT. Because the timing of the disruption was early enough to make it relevant to acute thrombolytic therapy, early BBB disruption as defined by this imaging biomarker may be a promising target for adjunctive therapy to reduce the complications associated with thrombolytic therapy, broaden the therapeutic window, and improve clinical outcome. Ann Neurol 2004
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Early blood–Brain barrier disruption in human Focal Brain Ischemia
Annals of Neurology, 2004Co-Authors: Lawrence L Latour, Dongwha Kang, Mustapha A Ezzeddine, Julio A Chalela, Steven WarachAbstract:Loss of integrity of the blood–Brain barrier (BBB) resulting from Ischemia/reperfusion is believed to be a precursor to hemorrhagic transformation (HT) and poor outcome. We used a novel magnetic resonance imaging marker to characterize early BBB disruption in human Focal Brain Ischemia and tested for associations with reperfusion, HT, and poor outcome (modified Rankin score >2). BBB disruption was found in 47 of 144 (33%) patients, having a median time from stroke onset to observation of 10.1 hours. Reperfusion was found to be the most powerful independent predictor of early BBB disruption (p = 0.018; odds ratio, 4.09; 95% confidence interval, 1.28–13.1). HT was observed in 22 patients; 16 (72.7%) of those also had early BBB disruption (p 6), early BBB disruption was found to be an independent predictor of HT. Because the timing of the disruption was early enough to make it relevant to acute thrombolytic therapy, early BBB disruption as defined by this imaging biomarker may be a promising target for adjunctive therapy to reduce the complications associated with thrombolytic therapy, broaden the therapeutic window, and improve clinical outcome. Ann Neurol 2004
Marc Fisher - One of the best experts on this subject based on the ideXlab platform.
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animal models of Focal Brain Ischemia
Experimental & Translational Stroke Medicine, 2009Co-Authors: Kenneth M Sicard, Marc FisherAbstract:Stroke is a leading cause of disability and death in many countries. Understanding the pathophysiology of ischemic injury and developing therapies is an important endeavor that requires much additional research. Animal stroke models provide an important mechanism for these activities. A large number of stroke models have been developed and are currently used in laboratories around the world. These models are overviewed as are approaches for measuring infarct size and functional outcome.
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secondary decline in apparent diffusion coefficient and neurological outcomes after a short period of Focal Brain Ischemia in rats
Annals of Neurology, 2000Co-Authors: Fuhai Li, Christopher H Sotak, Matthew D Silva, Karl G Helmer, T Omae, Joseph D Fenstermacher, Marc FisherAbstract:This study was designed to characterize the initial and secondary changes of the apparent diffusion coefficient (ADC) of water with high temporal resolution measurements of ADC values and to correlate ADC changes with functional outcomes. Fourteen rats underwent 30 minutes of temporary middle cerebral artery occlusion (MCAO). Diffusion-, perfusion-, and T2-weighted imaging was performed during MCAO and every 30 minutes for a total of 12 hours after reperfusion (n = 6). Neurological outcomes were evaluated during MCAO, every 30 minutes for a total of 6 hours and at 24 hours after reperfusion (n = 8). The decreased cerebral blood flow during MCAO returned to normal after reperfusion and remained unchanged thereafter. The decreased ADC values during occlusion completely recovered at 1 hour after reperfusion. The renormalized ADC values started to decrease secondarily at 2.5 hours, accompanied by a delayed increase in T2 values. The ADC-defined secondary lesion grew over time and was 52% of the ADC-defined initial lesion at 12 hours. Histological evaluation demonstrated neuronal damage in the regions of secondary ADC decline. Complete resolution of neurological deficits was seen in 1 rat at 1 hour and in 6 rats between 2.5 and 6 hours after reperfusion; no secondary neurological deficits were observed at 24 hours. These data suggest that (1) a secondary ADC reduction occurs as early as 2.5 hours after reperfusion, evolves in a slow fashion, and is associated with neuronal injury; and (2) renormalization and secondary decline in ADC are not associated with neurological recovery and worsening, respectively. Ann Neurol 2000;48:236–244
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mri diffusion mapping of reversible and irreversible ischemic injury in Focal Brain Ischemia
Neurology, 1994Co-Authors: Yasuhiro Hasegawa, Lawrence L Latour, Marc Fisher, Bernard J Dardzinski, Christopher H SotakAbstract:The reduction of the apparent diffusion coefficient (ADC) of water shortly after a Focal ischemic insult is thought to reflect intracellular water accumulation (cytotoxic edema) related to high-energy metabolism failure and loss of ion homeostasis. We attempted to clarify whether varying ranges of ADC measurements in ischemic Brain tissue can be used to differentiate between reversible and irreversible ischemic lesions before reperfusion in a temporary Ischemia model. We induced 45 minutes of temporary Ischemia in 12 rats using the middle cerebral artery suture occlusion method. Regional changes of ADC values were serially measured in seven regions of interest in each hemisphere and evaluated by ΔADC, defined as the difference between ADC value in an ischemic region and that in a contralateral homologous region. We acquired dynamic contrast-enhanced perfusion images 2 minutes before and after reperfusion to document reduced perfusion and its restoration. We confirmed the infarct area by 2,3,5-triphenyltetrazolium chloride staining 24 hours after occlusion and correlated this with the MRI studies. Recovery of initially reduced ADC values occurred only in ischemic regions where ΔADC values were not below −0.25 × 10 −5 cm 2 /sec. Although the extent of infarction at postmortem examination varied in regions with moderately decreased prereperfusion ADC values, more than 70% of regions of interest with slight declines of prereperfusion ADC values exhibited no infarction. ADC values progressively decreased after reperfusion in regions that initially had severely decreased prereperfusion ADC values, and postmortem examination always demonstrated infarction in such regions. These results suggest that measurement of ΔADC can provide information that will enable the clinician to discriminate between irreversible and potentially reversible ischemic regions before reperfusion is performed.
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diffusion weighted magnetic resonance imaging rapid and quantitative detection of Focal Brain Ischemia
Neurology, 1992Co-Authors: Kazuo Minematsu, Marc Fisher, Limin Li, Christopher H Sotak, Michael A Davis, Massimo S FiandacaAbstract:We examined serial changes of diffusion- (DWI) and T 2 -weighted (T2WI) magnetic resonance images 30 minutes to 3 hours after intraluminal suture occlusion of the middle cerebral artery (MCA) in eight rats and after sham occlusion in four. We correlated the abnormal areas on DWI and T2WI with postmortem areas of infarction determined by 2,3,5-triphenyltetrazolium chloride (TTC), 24 hours after the operation. The 30-minute DWI in each MCA-occluded rat demonstrated increased signal intensity in the ipsilateral MCA territory, while T2WI showed no changes. At 3 hours, the ipsilateral DWI signal intensity increased further and the area of abnormality slightly increased. In some animals, the 3-hour T2WI disclosed an area of hyperintensity significantly smaller than that seen on the 30-minute DWI. TTC staining demonstrated an extensive MCA infarction in all rats with permanent MCA occlusion, confirmed by hematoxylin and eosin staining. The percent infarcted area of coronal Brain sections, as determined by TTC staining, correlated significantly with areas on similar DWI sections at both 30 minutes and 3 hours. Sham-occluded control animals did not display any changes on DWI, T2WI, or TTC staining. The present study suggests that DWI is a very sensitive modality for detecting early ischemic Brain injury, being highly correlated with postmortem area of infarction, and may be useful to assess pharmacologic intervention.
David S. Baskin - One of the best experts on this subject based on the ideXlab platform.
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Caspase-3-Dependent and -Independent Apoptosis in Focal Brain Ischemia
Molecular Medicine, 2002Co-Authors: Vladimir V. Didenko, Candace L. Minchew, Denise J. Boudreaux, Marsha A. Widmayer, David S. BaskinAbstract:Background Although extensive caspase-3 activation has been demonstrated in experimental Brain Ischemia produced in neonatal rat, the role this caspase plays in the Focal Ischemia of adult Brain is not clear, as the levels of caspase-3 in adult rat Brain are extremely low. This raises the question whether caspase-3 synthesis and activation are essential for execution of the apoptotic program and DNA fragmentation in permanent Brain Ischemia, a condition that impairs cellular protein synthesis. Materials and Methods Rat middle cerebral artery was permanently occluded and histochemical detection of procaspase-3, active caspase-3 and DFF40/CAD and apoptotic morphology analysis were performed at 6, 24, 48, and 72 hours after occlusion. Results Necrosis and two types of programmed cell death (PCD) are identified in this study of permanent Focal Brain Ischemia. The first type of PCD is represented by active caspase-3 and DFF40/CAD-positive cells. The second type of PCD is represented by caspase-3 and DFF40/CAD negative cells, which display morphological signs of apoptosis-like PCD: namely, nuclear chromatin condensation in lump masses and apoptotic body formation. The cells of the first type have a maximum number noted after 24 hours of Ischemia. The cells of the second type are primarily seen after 48 and 72 hours of Ischemia. Necrotic cells, which are also detected in the stroke, are caspase-3 negative, and have swollen nuclei, without chromatin condensation and apoptotic body formation. Conclusions Our results indicate that in permanent Brain Ischemia in adult rats, PCD processes occur differently in various parts of ischemic zone. In conditions of severe energy depletion, the reactions of cellular disassembly and packaging into apoptotic bodies are accomplished without either caspase-3 expression or the activation of caspase-3-dependent deoxyribonuclease.
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Caspase-3-Dependent and -Independent Apoptosis in Focal Brain Ischemia
Molecular Medicine, 2002Co-Authors: Vladimir V. Didenko, Candace L. Minchew, Denise J. Boudreaux, Marsha A. Widmayer, David S. BaskinAbstract:Although extensive caspase-3 activation has been demonstrated in experimental Brain Ischemia produced in neonatal rat, the role this caspase plays in the Focal Ischemia of adult Brain is not clear, as the levels of caspase-3 in adult rat Brain are extremely low. This raises the question whether caspase-3 synthesis and activation are essential for execution of the apoptotic program and DNA fragmentation in permanent Brain Ischemia, a condition that impairs cellular protein synthesis. Rat middle cerebral artery was permanently occluded and histochemical detection of procaspase-3, active caspase-3 and DFF40/CAD and apoptotic morphology analysis were performed at 6, 24, 48, and 72 hours after occlusion. Necrosis and two types of programmed cell death (PCD) are identified in this study of permanent Focal Brain Ischemia. The first type of PCD is represented by active caspase-3 and DFF40/CAD-positive cells. The second type of PCD is represented by caspase-3 and DFF40/CAD negative cells, which display morphological signs of apoptosis-like PCD: namely, nuclear chromatin condensation in lump masses and apoptotic body formation. The cells of the first type have a maximum number noted after 24 hours of Ischemia. The cells of the second type are primarily seen after 48 and 72 hours of Ischemia. Necrotic cells, which are also detected in the stroke, are caspase-3 negative, and have swollen nuclei, without chromatin condensation and apoptotic body formation. Our results indicate that in permanent Brain Ischemia in adult rats, PCD processes occur differently in various parts of ischemic zone. In conditions of severe energy depletion, the reactions of cellular disassembly and packaging into apoptotic bodies are accomplished without either caspase-3 expression or the activation of caspase-3-dependent deoxyribonuclease.