The Experts below are selected from a list of 1152 Experts worldwide ranked by ideXlab platform

Brian S. Mckay - One of the best experts on this subject based on the ideXlab platform.

  • liquefaction of the brain following stroke shares a similar molecular and morphological profile with atherosclerosis and mediates secondary neurodegeneration in an osteopontin dependent mechanism
    eNeuro, 2018
    Co-Authors: Amanda Chung, Jacob C. Zbesko, Jennifer B. Frye, Megan Hayes, Eleni Constantopoulos, Anna G. Figueroa, John P. Konhilas, Danielle A Becktel, Antony W Day, Brian S. Mckay
    Abstract:

    Here we used mouse models of heart and brain ischemia to compare the inflammatory response to ischemia in the heart, a protein rich organ, to the inflammatory response to ischemia in the brain, a lipid rich organ. We report that ischemia-induced inflammation resolves between one and four weeks in the heart compared to between eight and 24 weeks in the brain. Importantly, we discovered that a second burst of inflammation occurs in the brain between four and eight weeks following ischemia, which coincided with the appearance of cholesterol crystals within the infarct. This second wave shares a similar cellular and molecular profile with atherosclerosis and is characterized by high levels of osteopontin (OPN) and matrix metalloproteinases (MMPs). In order to test the role of OPN in areas of Liquefactive Necrosis, OPN-/- mice were subjected to brain ischemia. We found that at seven weeks following stroke, the expression of pro-inflammatory proteins and MMPs was profoundly reduced in the infarct of the OPN-/- mice, although the number of cholesterol crystals was increased. OPN-/- mice exhibited faster recovery of motor function and a higher number of neuronal nuclei (NeuN) positive cells in the peri-infarct area at seven weeks following stroke. Based on these findings we propose that the brain liquefies after stroke because phagocytic cells in the infarct are unable to efficiently clear cholesterol rich myelin debris, and that this leads to the perpetuation of an OPN-dependent inflammatory response characterized by high levels of degradative enzymes.

  • Liquefaction of the brain following stroke shares a similar molecular and morphological profile with atherosclerosis and mediates secondary neurodegeneration in an osteopontin dependent mechanism
    2018
    Co-Authors: Amanda Chung, Jacob C. Zbesko, Jennifer B. Frye, Megan Hayes, Eleni Constantopoulos, Anna G. Figueroa, W. Antony Day, John P. Konhilas, Brian S. Mckay, Thuy-vi V. Nguyen
    Abstract:

    The response to ischemic injury in the brain is different to the response to ischemic injury in other organs and tissues. Almost exclusive to the brain, and for unknown reasons, dead tissue liquefies in response to ischemia by the process of Liquefactive Necrosis. However, the data we present here indicate that at the macroscopic, microscopic, and molecular level, Liquefactive Necrosis strongly resembles atherosclerosis. We show that chronic stroke infarcts contain foamy macrophages, cholesterol crystals, high levels of osteopontin and matrix metalloproteinases, and a similar cytokine profile to atherosclerosis. Excessive cholesterol loading of macrophages is a principal driver of atherosclerosis. Therefore, because cholesterol is an important structural component of myelin, Liquefactive Necrosis in response to stroke may be caused by an inflammatory response to myelin debris that is prolonged by the formation of cholesterol crystals within macrophages. We propose that this results in the chronic production of high levels of proteases, which in a partially osteopontin dependent mechanism, causes secondary neurodegeneration and encephalomalacia of the surrounding tissue. In support of this, we show that genetically ablating osteopontin substantially reduces the production of degradative enzymes following stroke, reduces secondary neurodegeneration, and improves recovery. These findings suggest that treatments that prevent atherosclerosis or target the regression of atherosclerosis may also be useful for mitigating the harmful effects of Liquefactive Necrosis following stroke.

H. Kitagawa - One of the best experts on this subject based on the ideXlab platform.

  • Delayed changes of vascular permeability in the cat's spinal cord following continuous electrical stimulation
    International Orthopaedics, 1991
    Co-Authors: Kazuhiko Takakuwa, Haruo Tsuji, Haruo Takano, H. Kitagawa
    Abstract:

    Liquefactive Necrosis coexistent with alteration of vascular permeability was studied following electrical stimulation of the spinal cord. Evans blue albumen complex (EBA) (2.5%) was perfused one hour before electrical stimulation for 30 min with 10 mA current of 0.3 msec duration at a frequency of 20 Hz. Perfusion with saline and formalin was carried out at 0, 1, 3, 6 and 12 h after stimulation had been completed. Results were independent of the time lapse after completion of the stimulation. Liquefactive Necrosis, swelling and moniliform degeneration and myelinoclasia of the myelin sheath were noted only in the external layer of the white matter. EBA leakage occurred, but there was no further expansion with time. Les auteurs ont étudié, après stimulation électrique de la moelle épinière, la nécrose liquéfiante avec altération de la perméabilité vasculaire. Un complexe (2.5%) d'albumine et de bleu Evans (ABE) a été perfusé une heure avant une stimulation électrique de 30 minutes par un courant de 10 mA, de 0.3 msec de durée, à une fréquence de 20 Hz. Une perfusion de sérum salé et de formaline a été effectuée 1, 2, 6 et 12 heures après que la stimulation ait été terminée. Les résultats sont indépendants du délai écoulé depuis la fin de la stimulation. On observe, au niveau seulement de la couche externe de la substance blanche, une nécrose liquéfiante, un oedème et une dégénérescence moniliforme, une myélinoclasie des gaînes des myéline. Une fuite de l'ABE s'est produite, mais elle n'augmente pas avec le temps.

  • Delayed changes of vascular permeability in the cat's spinal cord following continuous electrical stimulation.
    International Orthopaedics, 1991
    Co-Authors: Kazuhiko Takakuwa, Haruo Tsuji, Haruo Takano, H. Kitagawa
    Abstract:

    Liquefactive Necrosis coexistent with alteration of vascular permeability was studied following electrical stimulation of the spinal cord. Evans blue albumen complex (EBA) (2.5%) was perfused one hour before electrical stimulation for 30 min with 10 mA current of 0.3 msec duration at a frequency of 20 Hz. Perfusion with saline and formalin was carried out at 0, 1, 3, 6 and 12 h after stimulation had been completed. Results were independent of the time lapse after completion of the stimulation. Liquefactive Necrosis, swelling and moniliform degeneration and myelinoclasia of the myelin sheath were noted only in the external layer of the white matter. EBA leakage occurred, but there was no further expansion with time.

Amanda Chung - One of the best experts on this subject based on the ideXlab platform.

  • liquefaction of the brain following stroke shares a similar molecular and morphological profile with atherosclerosis and mediates secondary neurodegeneration in an osteopontin dependent mechanism
    eNeuro, 2018
    Co-Authors: Amanda Chung, Jacob C. Zbesko, Jennifer B. Frye, Megan Hayes, Eleni Constantopoulos, Anna G. Figueroa, John P. Konhilas, Danielle A Becktel, Antony W Day, Brian S. Mckay
    Abstract:

    Here we used mouse models of heart and brain ischemia to compare the inflammatory response to ischemia in the heart, a protein rich organ, to the inflammatory response to ischemia in the brain, a lipid rich organ. We report that ischemia-induced inflammation resolves between one and four weeks in the heart compared to between eight and 24 weeks in the brain. Importantly, we discovered that a second burst of inflammation occurs in the brain between four and eight weeks following ischemia, which coincided with the appearance of cholesterol crystals within the infarct. This second wave shares a similar cellular and molecular profile with atherosclerosis and is characterized by high levels of osteopontin (OPN) and matrix metalloproteinases (MMPs). In order to test the role of OPN in areas of Liquefactive Necrosis, OPN-/- mice were subjected to brain ischemia. We found that at seven weeks following stroke, the expression of pro-inflammatory proteins and MMPs was profoundly reduced in the infarct of the OPN-/- mice, although the number of cholesterol crystals was increased. OPN-/- mice exhibited faster recovery of motor function and a higher number of neuronal nuclei (NeuN) positive cells in the peri-infarct area at seven weeks following stroke. Based on these findings we propose that the brain liquefies after stroke because phagocytic cells in the infarct are unable to efficiently clear cholesterol rich myelin debris, and that this leads to the perpetuation of an OPN-dependent inflammatory response characterized by high levels of degradative enzymes.

  • Liquefaction of the brain following stroke shares a similar molecular and morphological profile with atherosclerosis and mediates secondary neurodegeneration in an osteopontin dependent mechanism
    2018
    Co-Authors: Amanda Chung, Jacob C. Zbesko, Jennifer B. Frye, Megan Hayes, Eleni Constantopoulos, Anna G. Figueroa, W. Antony Day, John P. Konhilas, Brian S. Mckay, Thuy-vi V. Nguyen
    Abstract:

    The response to ischemic injury in the brain is different to the response to ischemic injury in other organs and tissues. Almost exclusive to the brain, and for unknown reasons, dead tissue liquefies in response to ischemia by the process of Liquefactive Necrosis. However, the data we present here indicate that at the macroscopic, microscopic, and molecular level, Liquefactive Necrosis strongly resembles atherosclerosis. We show that chronic stroke infarcts contain foamy macrophages, cholesterol crystals, high levels of osteopontin and matrix metalloproteinases, and a similar cytokine profile to atherosclerosis. Excessive cholesterol loading of macrophages is a principal driver of atherosclerosis. Therefore, because cholesterol is an important structural component of myelin, Liquefactive Necrosis in response to stroke may be caused by an inflammatory response to myelin debris that is prolonged by the formation of cholesterol crystals within macrophages. We propose that this results in the chronic production of high levels of proteases, which in a partially osteopontin dependent mechanism, causes secondary neurodegeneration and encephalomalacia of the surrounding tissue. In support of this, we show that genetically ablating osteopontin substantially reduces the production of degradative enzymes following stroke, reduces secondary neurodegeneration, and improves recovery. These findings suggest that treatments that prevent atherosclerosis or target the regression of atherosclerosis may also be useful for mitigating the harmful effects of Liquefactive Necrosis following stroke.

  • Glial scars are permeable to the neurotoxic environment of chronic stroke infarcts.
    Neurobiology of Disease, 2018
    Co-Authors: Jacob C. Zbesko, Thuy-vi V. Nguyen, Tao Yang, Jennifer B. Frye, Omar Khadeer Hussain, Megan Hayes, Amanda Chung, W. Anthony Day, Kristina Stepanovic, Krumberger
    Abstract:

    Abstract Following stroke, the damaged tissue undergoes Liquefactive Necrosis, a stage of infarct resolution that lasts for months although the exact length of time is currently unknown. One method of repair involves reactive astrocytes and microglia forming a glial scar to compartmentalize the area of Liquefactive Necrosis from the rest of the brain. The formation of the glial scar is a critical component of the healing response to stroke, as well as other central nervous system (CNS) injuries. The goal of this study was to evaluate the toxicity of the extracellular fluid present in areas of Liquefactive Necrosis and determine how effectively it is segregated from the remainder of the brain. To accomplish this goal, we used a mouse model of stroke in conjunction with an extracellular fluid toxicity assay, fluorescent and electron microscopy, immunostaining, tracer injections into the infarct, and multiplex immunoassays. We confirmed that the extracellular fluid present in areas of Liquefactive Necrosis following stroke is toxic to primary cortical and hippocampal neurons for at least 7 weeks following stroke, and discovered that although glial scars are robust physical and endocytic barriers, they are nevertheless permeable. We found that molecules present in the area of Liquefactive Necrosis can leak across the glial scar and are removed by a combination of paravascular clearance and microglial endocytosis in the adjacent tissue. Despite these mechanisms, there is delayed atrophy, cytotoxic edema, and neuron loss in regions adjacent to the infarct for weeks following stroke. These findings suggest that one mechanism of neurodegeneration following stroke is the failure of glial scars to impermeably segregate areas of Liquefactive Necrosis from surviving brain tissue.

Jacob C. Zbesko - One of the best experts on this subject based on the ideXlab platform.

  • liquefaction of the brain following stroke shares a similar molecular and morphological profile with atherosclerosis and mediates secondary neurodegeneration in an osteopontin dependent mechanism
    eNeuro, 2018
    Co-Authors: Amanda Chung, Jacob C. Zbesko, Jennifer B. Frye, Megan Hayes, Eleni Constantopoulos, Anna G. Figueroa, John P. Konhilas, Danielle A Becktel, Antony W Day, Brian S. Mckay
    Abstract:

    Here we used mouse models of heart and brain ischemia to compare the inflammatory response to ischemia in the heart, a protein rich organ, to the inflammatory response to ischemia in the brain, a lipid rich organ. We report that ischemia-induced inflammation resolves between one and four weeks in the heart compared to between eight and 24 weeks in the brain. Importantly, we discovered that a second burst of inflammation occurs in the brain between four and eight weeks following ischemia, which coincided with the appearance of cholesterol crystals within the infarct. This second wave shares a similar cellular and molecular profile with atherosclerosis and is characterized by high levels of osteopontin (OPN) and matrix metalloproteinases (MMPs). In order to test the role of OPN in areas of Liquefactive Necrosis, OPN-/- mice were subjected to brain ischemia. We found that at seven weeks following stroke, the expression of pro-inflammatory proteins and MMPs was profoundly reduced in the infarct of the OPN-/- mice, although the number of cholesterol crystals was increased. OPN-/- mice exhibited faster recovery of motor function and a higher number of neuronal nuclei (NeuN) positive cells in the peri-infarct area at seven weeks following stroke. Based on these findings we propose that the brain liquefies after stroke because phagocytic cells in the infarct are unable to efficiently clear cholesterol rich myelin debris, and that this leads to the perpetuation of an OPN-dependent inflammatory response characterized by high levels of degradative enzymes.

  • Liquefaction of the brain following stroke shares a similar molecular and morphological profile with atherosclerosis and mediates secondary neurodegeneration in an osteopontin dependent mechanism
    2018
    Co-Authors: Amanda Chung, Jacob C. Zbesko, Jennifer B. Frye, Megan Hayes, Eleni Constantopoulos, Anna G. Figueroa, W. Antony Day, John P. Konhilas, Brian S. Mckay, Thuy-vi V. Nguyen
    Abstract:

    The response to ischemic injury in the brain is different to the response to ischemic injury in other organs and tissues. Almost exclusive to the brain, and for unknown reasons, dead tissue liquefies in response to ischemia by the process of Liquefactive Necrosis. However, the data we present here indicate that at the macroscopic, microscopic, and molecular level, Liquefactive Necrosis strongly resembles atherosclerosis. We show that chronic stroke infarcts contain foamy macrophages, cholesterol crystals, high levels of osteopontin and matrix metalloproteinases, and a similar cytokine profile to atherosclerosis. Excessive cholesterol loading of macrophages is a principal driver of atherosclerosis. Therefore, because cholesterol is an important structural component of myelin, Liquefactive Necrosis in response to stroke may be caused by an inflammatory response to myelin debris that is prolonged by the formation of cholesterol crystals within macrophages. We propose that this results in the chronic production of high levels of proteases, which in a partially osteopontin dependent mechanism, causes secondary neurodegeneration and encephalomalacia of the surrounding tissue. In support of this, we show that genetically ablating osteopontin substantially reduces the production of degradative enzymes following stroke, reduces secondary neurodegeneration, and improves recovery. These findings suggest that treatments that prevent atherosclerosis or target the regression of atherosclerosis may also be useful for mitigating the harmful effects of Liquefactive Necrosis following stroke.

  • Glial scars are permeable to the neurotoxic environment of chronic stroke infarcts.
    Neurobiology of Disease, 2018
    Co-Authors: Jacob C. Zbesko, Thuy-vi V. Nguyen, Tao Yang, Jennifer B. Frye, Omar Khadeer Hussain, Megan Hayes, Amanda Chung, W. Anthony Day, Kristina Stepanovic, Krumberger
    Abstract:

    Abstract Following stroke, the damaged tissue undergoes Liquefactive Necrosis, a stage of infarct resolution that lasts for months although the exact length of time is currently unknown. One method of repair involves reactive astrocytes and microglia forming a glial scar to compartmentalize the area of Liquefactive Necrosis from the rest of the brain. The formation of the glial scar is a critical component of the healing response to stroke, as well as other central nervous system (CNS) injuries. The goal of this study was to evaluate the toxicity of the extracellular fluid present in areas of Liquefactive Necrosis and determine how effectively it is segregated from the remainder of the brain. To accomplish this goal, we used a mouse model of stroke in conjunction with an extracellular fluid toxicity assay, fluorescent and electron microscopy, immunostaining, tracer injections into the infarct, and multiplex immunoassays. We confirmed that the extracellular fluid present in areas of Liquefactive Necrosis following stroke is toxic to primary cortical and hippocampal neurons for at least 7 weeks following stroke, and discovered that although glial scars are robust physical and endocytic barriers, they are nevertheless permeable. We found that molecules present in the area of Liquefactive Necrosis can leak across the glial scar and are removed by a combination of paravascular clearance and microglial endocytosis in the adjacent tissue. Despite these mechanisms, there is delayed atrophy, cytotoxic edema, and neuron loss in regions adjacent to the infarct for weeks following stroke. These findings suggest that one mechanism of neurodegeneration following stroke is the failure of glial scars to impermeably segregate areas of Liquefactive Necrosis from surviving brain tissue.

Jennifer B. Frye - One of the best experts on this subject based on the ideXlab platform.

  • liquefaction of the brain following stroke shares a similar molecular and morphological profile with atherosclerosis and mediates secondary neurodegeneration in an osteopontin dependent mechanism
    eNeuro, 2018
    Co-Authors: Amanda Chung, Jacob C. Zbesko, Jennifer B. Frye, Megan Hayes, Eleni Constantopoulos, Anna G. Figueroa, John P. Konhilas, Danielle A Becktel, Antony W Day, Brian S. Mckay
    Abstract:

    Here we used mouse models of heart and brain ischemia to compare the inflammatory response to ischemia in the heart, a protein rich organ, to the inflammatory response to ischemia in the brain, a lipid rich organ. We report that ischemia-induced inflammation resolves between one and four weeks in the heart compared to between eight and 24 weeks in the brain. Importantly, we discovered that a second burst of inflammation occurs in the brain between four and eight weeks following ischemia, which coincided with the appearance of cholesterol crystals within the infarct. This second wave shares a similar cellular and molecular profile with atherosclerosis and is characterized by high levels of osteopontin (OPN) and matrix metalloproteinases (MMPs). In order to test the role of OPN in areas of Liquefactive Necrosis, OPN-/- mice were subjected to brain ischemia. We found that at seven weeks following stroke, the expression of pro-inflammatory proteins and MMPs was profoundly reduced in the infarct of the OPN-/- mice, although the number of cholesterol crystals was increased. OPN-/- mice exhibited faster recovery of motor function and a higher number of neuronal nuclei (NeuN) positive cells in the peri-infarct area at seven weeks following stroke. Based on these findings we propose that the brain liquefies after stroke because phagocytic cells in the infarct are unable to efficiently clear cholesterol rich myelin debris, and that this leads to the perpetuation of an OPN-dependent inflammatory response characterized by high levels of degradative enzymes.

  • Liquefaction of the brain following stroke shares a similar molecular and morphological profile with atherosclerosis and mediates secondary neurodegeneration in an osteopontin dependent mechanism
    2018
    Co-Authors: Amanda Chung, Jacob C. Zbesko, Jennifer B. Frye, Megan Hayes, Eleni Constantopoulos, Anna G. Figueroa, W. Antony Day, John P. Konhilas, Brian S. Mckay, Thuy-vi V. Nguyen
    Abstract:

    The response to ischemic injury in the brain is different to the response to ischemic injury in other organs and tissues. Almost exclusive to the brain, and for unknown reasons, dead tissue liquefies in response to ischemia by the process of Liquefactive Necrosis. However, the data we present here indicate that at the macroscopic, microscopic, and molecular level, Liquefactive Necrosis strongly resembles atherosclerosis. We show that chronic stroke infarcts contain foamy macrophages, cholesterol crystals, high levels of osteopontin and matrix metalloproteinases, and a similar cytokine profile to atherosclerosis. Excessive cholesterol loading of macrophages is a principal driver of atherosclerosis. Therefore, because cholesterol is an important structural component of myelin, Liquefactive Necrosis in response to stroke may be caused by an inflammatory response to myelin debris that is prolonged by the formation of cholesterol crystals within macrophages. We propose that this results in the chronic production of high levels of proteases, which in a partially osteopontin dependent mechanism, causes secondary neurodegeneration and encephalomalacia of the surrounding tissue. In support of this, we show that genetically ablating osteopontin substantially reduces the production of degradative enzymes following stroke, reduces secondary neurodegeneration, and improves recovery. These findings suggest that treatments that prevent atherosclerosis or target the regression of atherosclerosis may also be useful for mitigating the harmful effects of Liquefactive Necrosis following stroke.

  • Glial scars are permeable to the neurotoxic environment of chronic stroke infarcts.
    Neurobiology of Disease, 2018
    Co-Authors: Jacob C. Zbesko, Thuy-vi V. Nguyen, Tao Yang, Jennifer B. Frye, Omar Khadeer Hussain, Megan Hayes, Amanda Chung, W. Anthony Day, Kristina Stepanovic, Krumberger
    Abstract:

    Abstract Following stroke, the damaged tissue undergoes Liquefactive Necrosis, a stage of infarct resolution that lasts for months although the exact length of time is currently unknown. One method of repair involves reactive astrocytes and microglia forming a glial scar to compartmentalize the area of Liquefactive Necrosis from the rest of the brain. The formation of the glial scar is a critical component of the healing response to stroke, as well as other central nervous system (CNS) injuries. The goal of this study was to evaluate the toxicity of the extracellular fluid present in areas of Liquefactive Necrosis and determine how effectively it is segregated from the remainder of the brain. To accomplish this goal, we used a mouse model of stroke in conjunction with an extracellular fluid toxicity assay, fluorescent and electron microscopy, immunostaining, tracer injections into the infarct, and multiplex immunoassays. We confirmed that the extracellular fluid present in areas of Liquefactive Necrosis following stroke is toxic to primary cortical and hippocampal neurons for at least 7 weeks following stroke, and discovered that although glial scars are robust physical and endocytic barriers, they are nevertheless permeable. We found that molecules present in the area of Liquefactive Necrosis can leak across the glial scar and are removed by a combination of paravascular clearance and microglial endocytosis in the adjacent tissue. Despite these mechanisms, there is delayed atrophy, cytotoxic edema, and neuron loss in regions adjacent to the infarct for weeks following stroke. These findings suggest that one mechanism of neurodegeneration following stroke is the failure of glial scars to impermeably segregate areas of Liquefactive Necrosis from surviving brain tissue.