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Gerhard F Hamann - One of the best experts on this subject based on the ideXlab platform.
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mild to moderate hypothermia prevents microvascular Basal Lamina antigen loss in experimental focal cerebral ischemia
Stroke, 2004Co-Authors: Gerhard F Hamann, Dorothe Burggraf, Helge K Martens, Gabriele Jager, Martin Liebetrau, Nathalie Wunderlich, Michael Degeorgia, Derk W KriegerAbstract:Background and Purpose— Microvascular Basal Lamina damage occurs after cerebral ischemia and is important for the development of hemorrhage. The aim of this study was to determine whether hypothermia could maintain microvascular integrity in ischemic stroke. Methods— Using the suture model, we subjected 12 rats to 3 hours of focal ischemia and 24 hours of reperfusion. Six rats received postischemic normothermia (37°C) and 6 received hypothermia (32°C to 34°C) for the reperfusion period; a group of 6 sham-operated animals without ischemia was used as control. Collagen type IV and hemoglobin were measured by Western blot analysis, matrix metalloproteinase (MMP)-2 and MMP-9 by gelatin zymography, and urokinase-type plasminogen activator (uPA) and tissue-type plasminogen activator (tPA) by plasminogen-casein zymography. Results— Hypothermia reduced Basal Lamina collagen type IV loss: 87±16% (hypothermia) versus 43±4% (normothermia) in Basal ganglia and 74±16% versus 64±4% in cortex; hypothermia reduced hemorrhage from 431±65% (normothermia) to 241±28% (Basal ganglia) ( P <0.05). Hypothermia also reduced MMP-2, MMP-9, uPA, and tPA (Basal ganglia: MMP-2: 71±20% [hypothermia] versus 109±3% [normothermia]; MMP-9: 38±12% versus 115±4%; uPA activity: 310±86% versus 1019±22%; tPA activity: 61±17% versus 111±13%; cortex: MMP-2: 53±6% versus 116±1%; MMP-9: 16±4% versus 123±3%; uPA: 180±27% versus 176±10%; tPA: 91±15% versus 101±8%; each difference: P <0.001) (nonischemic control side=100%). Conclusions— Hypothermia maintains microvascular integrity and reduces hemorrhage and the activities of MMP-2, MMP-9, uPA, and tPA.
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recombinant human tissue plasminogen activator protects the Basal Lamina in experimental focal cerebral ischemia
Thrombosis and Haemostasis, 2003Co-Authors: Dorothe Burggraf, Helge K Martens, Gabriele Jager, Gerhard F HamannAbstract:While recombinant tissue plasminogen activator (rt-PA) is successfully used in human ischemic stroke, it may also cause hemorrhagic complications. Animal experiments have shown that hemorrhages are related to microvascular Basal Lamina damage.We investigated the effects of different doses of rt-PA on the brain microvasculature. Experimental cerebral ischemia in rats was induced for 3 h and followed by 24 h reperfusion (suture model). Each group of rats (n = 6) received either treatment (0.9, 9, or 18 mg rt-PA/kg body weight) or saline (control group) at the end of ischemia. The loss of microvascular Basal Lamina antigen collagen type IV was measured by Western blot of the ischemic and non-ischemic Basal ganglia and cortex. Compared with the contralateral non-ischemic area, collagen type IV was significantly reduced in the ischemic area: (Basal ganglia/cortex) 43% +/- 9% / 64% +/- 4 %. Low/moderate doses of rt-PA had a protective effect: 0.9 mg 79% +/- 3% / 89% +/- 6%, 9 mg 72% +/- 9%/ 81% +/- 12% (p < 0.05). Higher doses of rt-PA (18 mg) had a similar effect as seen in untreated controls: 57% +/- 11% / 59% +/- 9% (p < 0.05,Anova). MMP-9 and MMP- 2, measured by gelatine zymography, steadily increased over higher doses of rt-PA: MMP-9 (Basal ganglia/cortex): control 115% +/- 4% / 123% +/- 3% compared with 18 mg rt-PA 146% +/- 5%/ 162% +/- 6% (p < 0.05) and MMP-2: control 109% +/- 4%/ 116% +/- 5% and 18 mg rt-PA 222% +/- 15%/ 252% +/- 2% (p < 0.05). Low to moderate doses of rt-PA protect the microvascular Basal Lamina, whereas high doses of rt-PA have the opposite effect, probably due to increased coactivation of MMP-2 and MMP-9.
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microvascular Basal Lamina injury after experimental focal cerebral ischemia and reperfusion in the rat
Journal of Cerebral Blood Flow and Metabolism, 2002Co-Authors: Gerhard F Hamann, Dorothe Burggraf, Helge K Martens, Gabriele Jager, Martin Liebetrau, Christian U A Kloss, G Bultemeier, Natalie Wunderlich, Thomas PfefferkornAbstract:To define the location and extent of microvascular damage of the Basal Lamina after cerebral ischemia and reperfusion in rats, the authors subjected animals (n = 16) to 3 hours of focal cerebral ischemia and 24 hours of reperfusion using the suture middle cerebral artery occlusion model; sham-operated animals served as controls (n = 6). The Western blot technique was used to define the collagen type IV protein content in various brain regions, whereas immunohistochemistry identified microvascular Basal Lamina loss (anticollagen type IV staining). The extent of damage was quantified by automatic morphometric video-imaging analysis. Statistical analysis was based on the Mann-Whitney test and the paired Student's t-test. The ischemic hemisphere showed a reduction of the collagen type IV protein content after ischemia and reperfusion in the Western blot (reduction compared with the nonischemic side: total hemisphere, 33% +/- 6%; Basal ganglia, 25% +/- 7%; cortex 49% +/- 4%; P < 0.01) [corrected]. There was also a decrease in the number of cerebral microvessels between the ischemic and nonischemic hemispheres (20% +/- 2%), cortical (8% +/- 3%), and Basal ganglia areas (31% +/- 3%) (P < 0.001). Besides a reduction of the vessel number, there was also a loss in Basal Lamina antigen-positive stained area in ischemic areas (hemisphere, 16% +/- 3%; cortex, 14% +/- 3%; Basal ganglia, 21% +/- 4%; P < 0.01) [corrected]. Cortical areas had a less pronounced Basal Lamina loss than Basal ganglia (P < 0.05). For the first time, microvascular Basal Lamina damage, indicated by collagen type IV loss, is proven in rats by biochemical and morphometric analysis. These changes are comparable with those found in nonhuman primates. The authors report novel data regarding microvascular ischemic changes in the cortex. These data provide a basis for future experiments to determine the mechanisms of ischemic microvascular damage and to devise new therapeutic strategies.
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microvascular Basal Lamina injury after experimental focal cerebral ischemia and reperfusion in the rat
Journal of Cerebral Blood Flow and Metabolism, 2002Co-Authors: Gerhard F Hamann, Dorothe Burggraf, Helge K Martens, Gabriele Jager, Martin Liebetrau, Christian U A Kloss, G Bultemeier, Natalie Wunderlich, Thomas PfefferkornAbstract:To define the location and extent of microvascular damage of the Basal Lamina after cerebral ischemia and reperfusion in rats, the authors subjected animals (n = 16) to 3 hours of focal cerebral ischemia and 24 hours of reperfusion using the suture middle cerebral artery occlusion model; sham-operated animals served as controls (n = 6). The Western blot technique was used to define the collagen type IV protein content in various brain regions, whereas immunohistochemistry identified microvascular Basal Lamina loss (anticollagen type IV staining). The extent of damage was quantified by automatic morphometric video-imaging analysis. Statistical analysis was based on the Mann-Whitney test and the paired Student's t-test. The ischemic hemisphere showed a reduction of the collagen type IV protein content after ischemia and reperfusion in the Western blot (reduction compared with the nonischemic side: total hemisphere, 33% ± 6%; Basal ganglia, 49% ± 4%; cortex, 25% ± 7%; P < 0.01). There was also a decrease in ...
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microvascular Basal Lamina antigens disappear during cerebral ischemia and reperfusion
Stroke, 1995Co-Authors: Gerhard F Hamann, Yasushi Okada, Robert Fitridge, Gregory J Del ZoppoAbstract:Background and Purpose Changes in vascular permeability are well-known and important consequences of cerebral ischemia. The development of edema and of petechial hemorrhage is connected to altered vascular integrity. A major part in microvascular integrity is played by the Basal Lamina. Methods The fates of the Basal Lamina components laminin, fibronectin, and type IV collagen during middle cerebral artery occlusion (2 hours, n=3) and occlusion (3 hours) with reperfusion (1 hour, n=3; 4 hours, n=3; and 24 hours, n=4) were evaluated in the nonhuman primate. Specific monoclonal antibodies against these components were used. The number and size distribution of the microvessels in each specimen were determined by video-imaging microscopy, and the relative fluorescence intensity of laminin was semiquantified by laser confocal microscopy. Basal Lamina antigen presentations were compared by double-stain immunofluorescence histochemistry. Results The number of microvascular structures defined by the presence of each Basal Lamina antigen decreased significantly up to 24 hours of reperfusion ( P <.0001). The ratio of laminin-containing vessels between the ischemic and nonischemic territories decreased significantly from control (0.98±0.04) to 2 hours of ischemia (0.83±0.09) and 1 hour (0.79±0.08), 4 hours (0.77±0.06), and 24 hours of reperfusion (0.55±0.07). The ratio of fibronectin (cellular) and of collagen (IV)-containing vessels decreased from 0.98±0.04 to 0.75±0.1 and from 1.02±0.03 to 0.57±0.1, respectively. Mean laminin fluorescence intensity decreased from 76.1±6.0 U (controls) to 52.0±14.6 U (24 hours of reperfusion; P <.001). Conclusions The significant parallel losses of three Basal Lamina components, both in number and intensity, contribute to loss of microvascular integrity. These phenomena may be important for understanding cell extravasation and the hemorrhagic consequences of acute stroke.
Mariajulieta Gonzalez - One of the best experts on this subject based on the ideXlab platform.
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involvement of specific laminins and nidogens in the active remodeling of the Basal Lamina of labial salivary glands from patients with sjogren s syndrome
Arthritis & Rheumatism, 2006Co-Authors: Yoonjeoung Kwon, Claudio Molina, Cecilia Alliende, Sergio Aguilera, Lisette Leyton, Cecilia Leyton, Paola Perez, Monica Brito, Rafael Romo, Mariajulieta GonzalezAbstract:Objective To investigate remodeling of the Basal Lamina of labial salivary glands (LSGs) from patients with Sjogren's syndrome (SS) by analyzing the expression of specific components that participate in its assembly and attachment to acinar and ductal cells. Methods Two groups of SS patients with similar levels of remnant glandular tissue but with low and high levels of interacinar fibrosis, respectively, were studied. The expression of laminin α1, α4, and γ2 chains and nidogens was examined at the messenger RNA (mRNA) and protein levels. Nidogens 1 and 2 were also studied in situ by immunohistochemistry. Results Increases in the amount of mRNA and protein for both the processed and unprocessed laminin γ2-chain were more pronounced in patients with low interacinar fibrosis. Increases in the protein levels of laminin α1 and α4 chains were observed in patients with low interacinar fibrosis, but not in those with high interacinar fibrosis. Nidogen mRNA and protein levels were similar in SS patients and controls. Interestingly, high levels of nidogen degradation were observed in patients with low interacinar fibrosis. Nidogens were readily detected by immunofluorescence in the Basal Lamina of the capillaries and stroma in SS patients, but were less apparent in the Basal Lamina of the acini and ducts. Conclusion These results suggest that the Basal Lamina of LSGs from patients with SS is undergoing active remodeling, such that alterations are less evident in patients who have advanced morphologic signs of the disease (high interacinar fibrosis). Nidogen proteolysis might account for the disorganization of the Basal Lamina that is typically observed in LSGs from SS patients, assuming that cleavage impairs their ability to crosslink type IV collagen and laminin networks.
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Basal Lamina disorganisation of the acini and ducts of labial salivary glands from patients with sjogren s syndrome association with mononuclear cell infiltration
Annals of the Rheumatic Diseases, 2006Co-Authors: Claudio Molina, Cecilia Alliende, Sergio Aguilera, Yoonjeoung Kwon, Lisette Leyton, Benjamin Martinez, Cecilia Leyton, Paola Perez, Mariajulieta GonzalezAbstract:Objective: To study the expression of laminin and type IV collagen as biomarkers of the organisation of the Basal Lamina of acini and ducts in labial salivary glands from patients with Sjogren’s syndrome, and to relate this organisation to inflammatory cell invasion of acini and ducts. Methods: Immunohistochemistry for laminin and type IV collagen was undertaken on sections of labial salivary glands from 30 patients with Sjogren’s syndrome, 10 control subjects, and 24 controls with chronic sialoadenitis. Immunohistochemistry reaction, alterations to cell morphology, and the presence of inflammatory cells in acini and ducts were evaluated and scored using a semiquantitative method. Results: Changes in the expression of laminin and type IV collagen in the Basal Lamina of acini and ducts of labial salivary glands from patients with Sjogren’s syndrome were more pronounced than in labial salivary glands from control groups. A remarkable characteristic was the disorganisation of the Basal Lamina in the labial salivary glands in Sjogren’s syndrome. The pattern of immunoreactivity of the Basal Lamina of other structures (for example, blood vessels) did not change. In Sjogren’s syndrome, invasion of cytotoxic T lymphocytes was only observed in acini and ducts which had a disorganised Basal Lamina. Conclusions: The high state of disorganisation of the Basal Lamina of acini and ducts could allow invasion of cytotoxic T lymphocytes in Sjogren’s syndrome, contributing to cell death and ductal hyperplasia.
Dorothe Burggraf - One of the best experts on this subject based on the ideXlab platform.
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mild to moderate hypothermia prevents microvascular Basal Lamina antigen loss in experimental focal cerebral ischemia
Stroke, 2004Co-Authors: Gerhard F Hamann, Dorothe Burggraf, Helge K Martens, Gabriele Jager, Martin Liebetrau, Nathalie Wunderlich, Michael Degeorgia, Derk W KriegerAbstract:Background and Purpose— Microvascular Basal Lamina damage occurs after cerebral ischemia and is important for the development of hemorrhage. The aim of this study was to determine whether hypothermia could maintain microvascular integrity in ischemic stroke. Methods— Using the suture model, we subjected 12 rats to 3 hours of focal ischemia and 24 hours of reperfusion. Six rats received postischemic normothermia (37°C) and 6 received hypothermia (32°C to 34°C) for the reperfusion period; a group of 6 sham-operated animals without ischemia was used as control. Collagen type IV and hemoglobin were measured by Western blot analysis, matrix metalloproteinase (MMP)-2 and MMP-9 by gelatin zymography, and urokinase-type plasminogen activator (uPA) and tissue-type plasminogen activator (tPA) by plasminogen-casein zymography. Results— Hypothermia reduced Basal Lamina collagen type IV loss: 87±16% (hypothermia) versus 43±4% (normothermia) in Basal ganglia and 74±16% versus 64±4% in cortex; hypothermia reduced hemorrhage from 431±65% (normothermia) to 241±28% (Basal ganglia) ( P <0.05). Hypothermia also reduced MMP-2, MMP-9, uPA, and tPA (Basal ganglia: MMP-2: 71±20% [hypothermia] versus 109±3% [normothermia]; MMP-9: 38±12% versus 115±4%; uPA activity: 310±86% versus 1019±22%; tPA activity: 61±17% versus 111±13%; cortex: MMP-2: 53±6% versus 116±1%; MMP-9: 16±4% versus 123±3%; uPA: 180±27% versus 176±10%; tPA: 91±15% versus 101±8%; each difference: P <0.001) (nonischemic control side=100%). Conclusions— Hypothermia maintains microvascular integrity and reduces hemorrhage and the activities of MMP-2, MMP-9, uPA, and tPA.
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recombinant human tissue plasminogen activator protects the Basal Lamina in experimental focal cerebral ischemia
Thrombosis and Haemostasis, 2003Co-Authors: Dorothe Burggraf, Helge K Martens, Gabriele Jager, Gerhard F HamannAbstract:While recombinant tissue plasminogen activator (rt-PA) is successfully used in human ischemic stroke, it may also cause hemorrhagic complications. Animal experiments have shown that hemorrhages are related to microvascular Basal Lamina damage.We investigated the effects of different doses of rt-PA on the brain microvasculature. Experimental cerebral ischemia in rats was induced for 3 h and followed by 24 h reperfusion (suture model). Each group of rats (n = 6) received either treatment (0.9, 9, or 18 mg rt-PA/kg body weight) or saline (control group) at the end of ischemia. The loss of microvascular Basal Lamina antigen collagen type IV was measured by Western blot of the ischemic and non-ischemic Basal ganglia and cortex. Compared with the contralateral non-ischemic area, collagen type IV was significantly reduced in the ischemic area: (Basal ganglia/cortex) 43% +/- 9% / 64% +/- 4 %. Low/moderate doses of rt-PA had a protective effect: 0.9 mg 79% +/- 3% / 89% +/- 6%, 9 mg 72% +/- 9%/ 81% +/- 12% (p < 0.05). Higher doses of rt-PA (18 mg) had a similar effect as seen in untreated controls: 57% +/- 11% / 59% +/- 9% (p < 0.05,Anova). MMP-9 and MMP- 2, measured by gelatine zymography, steadily increased over higher doses of rt-PA: MMP-9 (Basal ganglia/cortex): control 115% +/- 4% / 123% +/- 3% compared with 18 mg rt-PA 146% +/- 5%/ 162% +/- 6% (p < 0.05) and MMP-2: control 109% +/- 4%/ 116% +/- 5% and 18 mg rt-PA 222% +/- 15%/ 252% +/- 2% (p < 0.05). Low to moderate doses of rt-PA protect the microvascular Basal Lamina, whereas high doses of rt-PA have the opposite effect, probably due to increased coactivation of MMP-2 and MMP-9.
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microvascular Basal Lamina injury after experimental focal cerebral ischemia and reperfusion in the rat
Journal of Cerebral Blood Flow and Metabolism, 2002Co-Authors: Gerhard F Hamann, Dorothe Burggraf, Helge K Martens, Gabriele Jager, Martin Liebetrau, Christian U A Kloss, G Bultemeier, Natalie Wunderlich, Thomas PfefferkornAbstract:To define the location and extent of microvascular damage of the Basal Lamina after cerebral ischemia and reperfusion in rats, the authors subjected animals (n = 16) to 3 hours of focal cerebral ischemia and 24 hours of reperfusion using the suture middle cerebral artery occlusion model; sham-operated animals served as controls (n = 6). The Western blot technique was used to define the collagen type IV protein content in various brain regions, whereas immunohistochemistry identified microvascular Basal Lamina loss (anticollagen type IV staining). The extent of damage was quantified by automatic morphometric video-imaging analysis. Statistical analysis was based on the Mann-Whitney test and the paired Student's t-test. The ischemic hemisphere showed a reduction of the collagen type IV protein content after ischemia and reperfusion in the Western blot (reduction compared with the nonischemic side: total hemisphere, 33% +/- 6%; Basal ganglia, 25% +/- 7%; cortex 49% +/- 4%; P < 0.01) [corrected]. There was also a decrease in the number of cerebral microvessels between the ischemic and nonischemic hemispheres (20% +/- 2%), cortical (8% +/- 3%), and Basal ganglia areas (31% +/- 3%) (P < 0.001). Besides a reduction of the vessel number, there was also a loss in Basal Lamina antigen-positive stained area in ischemic areas (hemisphere, 16% +/- 3%; cortex, 14% +/- 3%; Basal ganglia, 21% +/- 4%; P < 0.01) [corrected]. Cortical areas had a less pronounced Basal Lamina loss than Basal ganglia (P < 0.05). For the first time, microvascular Basal Lamina damage, indicated by collagen type IV loss, is proven in rats by biochemical and morphometric analysis. These changes are comparable with those found in nonhuman primates. The authors report novel data regarding microvascular ischemic changes in the cortex. These data provide a basis for future experiments to determine the mechanisms of ischemic microvascular damage and to devise new therapeutic strategies.
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microvascular Basal Lamina injury after experimental focal cerebral ischemia and reperfusion in the rat
Journal of Cerebral Blood Flow and Metabolism, 2002Co-Authors: Gerhard F Hamann, Dorothe Burggraf, Helge K Martens, Gabriele Jager, Martin Liebetrau, Christian U A Kloss, G Bultemeier, Natalie Wunderlich, Thomas PfefferkornAbstract:To define the location and extent of microvascular damage of the Basal Lamina after cerebral ischemia and reperfusion in rats, the authors subjected animals (n = 16) to 3 hours of focal cerebral ischemia and 24 hours of reperfusion using the suture middle cerebral artery occlusion model; sham-operated animals served as controls (n = 6). The Western blot technique was used to define the collagen type IV protein content in various brain regions, whereas immunohistochemistry identified microvascular Basal Lamina loss (anticollagen type IV staining). The extent of damage was quantified by automatic morphometric video-imaging analysis. Statistical analysis was based on the Mann-Whitney test and the paired Student's t-test. The ischemic hemisphere showed a reduction of the collagen type IV protein content after ischemia and reperfusion in the Western blot (reduction compared with the nonischemic side: total hemisphere, 33% ± 6%; Basal ganglia, 49% ± 4%; cortex, 25% ± 7%; P < 0.01). There was also a decrease in ...
Claudio Molina - One of the best experts on this subject based on the ideXlab platform.
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involvement of specific laminins and nidogens in the active remodeling of the Basal Lamina of labial salivary glands from patients with sjogren s syndrome
Arthritis & Rheumatism, 2006Co-Authors: Yoonjeoung Kwon, Claudio Molina, Cecilia Alliende, Sergio Aguilera, Lisette Leyton, Cecilia Leyton, Paola Perez, Monica Brito, Rafael Romo, Mariajulieta GonzalezAbstract:Objective To investigate remodeling of the Basal Lamina of labial salivary glands (LSGs) from patients with Sjogren's syndrome (SS) by analyzing the expression of specific components that participate in its assembly and attachment to acinar and ductal cells. Methods Two groups of SS patients with similar levels of remnant glandular tissue but with low and high levels of interacinar fibrosis, respectively, were studied. The expression of laminin α1, α4, and γ2 chains and nidogens was examined at the messenger RNA (mRNA) and protein levels. Nidogens 1 and 2 were also studied in situ by immunohistochemistry. Results Increases in the amount of mRNA and protein for both the processed and unprocessed laminin γ2-chain were more pronounced in patients with low interacinar fibrosis. Increases in the protein levels of laminin α1 and α4 chains were observed in patients with low interacinar fibrosis, but not in those with high interacinar fibrosis. Nidogen mRNA and protein levels were similar in SS patients and controls. Interestingly, high levels of nidogen degradation were observed in patients with low interacinar fibrosis. Nidogens were readily detected by immunofluorescence in the Basal Lamina of the capillaries and stroma in SS patients, but were less apparent in the Basal Lamina of the acini and ducts. Conclusion These results suggest that the Basal Lamina of LSGs from patients with SS is undergoing active remodeling, such that alterations are less evident in patients who have advanced morphologic signs of the disease (high interacinar fibrosis). Nidogen proteolysis might account for the disorganization of the Basal Lamina that is typically observed in LSGs from SS patients, assuming that cleavage impairs their ability to crosslink type IV collagen and laminin networks.
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Basal Lamina disorganisation of the acini and ducts of labial salivary glands from patients with sjogren s syndrome association with mononuclear cell infiltration
Annals of the Rheumatic Diseases, 2006Co-Authors: Claudio Molina, Cecilia Alliende, Sergio Aguilera, Yoonjeoung Kwon, Lisette Leyton, Benjamin Martinez, Cecilia Leyton, Paola Perez, Mariajulieta GonzalezAbstract:Objective: To study the expression of laminin and type IV collagen as biomarkers of the organisation of the Basal Lamina of acini and ducts in labial salivary glands from patients with Sjogren’s syndrome, and to relate this organisation to inflammatory cell invasion of acini and ducts. Methods: Immunohistochemistry for laminin and type IV collagen was undertaken on sections of labial salivary glands from 30 patients with Sjogren’s syndrome, 10 control subjects, and 24 controls with chronic sialoadenitis. Immunohistochemistry reaction, alterations to cell morphology, and the presence of inflammatory cells in acini and ducts were evaluated and scored using a semiquantitative method. Results: Changes in the expression of laminin and type IV collagen in the Basal Lamina of acini and ducts of labial salivary glands from patients with Sjogren’s syndrome were more pronounced than in labial salivary glands from control groups. A remarkable characteristic was the disorganisation of the Basal Lamina in the labial salivary glands in Sjogren’s syndrome. The pattern of immunoreactivity of the Basal Lamina of other structures (for example, blood vessels) did not change. In Sjogren’s syndrome, invasion of cytotoxic T lymphocytes was only observed in acini and ducts which had a disorganised Basal Lamina. Conclusions: The high state of disorganisation of the Basal Lamina of acini and ducts could allow invasion of cytotoxic T lymphocytes in Sjogren’s syndrome, contributing to cell death and ductal hyperplasia.
Helge K Martens - One of the best experts on this subject based on the ideXlab platform.
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mild to moderate hypothermia prevents microvascular Basal Lamina antigen loss in experimental focal cerebral ischemia
Stroke, 2004Co-Authors: Gerhard F Hamann, Dorothe Burggraf, Helge K Martens, Gabriele Jager, Martin Liebetrau, Nathalie Wunderlich, Michael Degeorgia, Derk W KriegerAbstract:Background and Purpose— Microvascular Basal Lamina damage occurs after cerebral ischemia and is important for the development of hemorrhage. The aim of this study was to determine whether hypothermia could maintain microvascular integrity in ischemic stroke. Methods— Using the suture model, we subjected 12 rats to 3 hours of focal ischemia and 24 hours of reperfusion. Six rats received postischemic normothermia (37°C) and 6 received hypothermia (32°C to 34°C) for the reperfusion period; a group of 6 sham-operated animals without ischemia was used as control. Collagen type IV and hemoglobin were measured by Western blot analysis, matrix metalloproteinase (MMP)-2 and MMP-9 by gelatin zymography, and urokinase-type plasminogen activator (uPA) and tissue-type plasminogen activator (tPA) by plasminogen-casein zymography. Results— Hypothermia reduced Basal Lamina collagen type IV loss: 87±16% (hypothermia) versus 43±4% (normothermia) in Basal ganglia and 74±16% versus 64±4% in cortex; hypothermia reduced hemorrhage from 431±65% (normothermia) to 241±28% (Basal ganglia) ( P <0.05). Hypothermia also reduced MMP-2, MMP-9, uPA, and tPA (Basal ganglia: MMP-2: 71±20% [hypothermia] versus 109±3% [normothermia]; MMP-9: 38±12% versus 115±4%; uPA activity: 310±86% versus 1019±22%; tPA activity: 61±17% versus 111±13%; cortex: MMP-2: 53±6% versus 116±1%; MMP-9: 16±4% versus 123±3%; uPA: 180±27% versus 176±10%; tPA: 91±15% versus 101±8%; each difference: P <0.001) (nonischemic control side=100%). Conclusions— Hypothermia maintains microvascular integrity and reduces hemorrhage and the activities of MMP-2, MMP-9, uPA, and tPA.
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recombinant human tissue plasminogen activator protects the Basal Lamina in experimental focal cerebral ischemia
Thrombosis and Haemostasis, 2003Co-Authors: Dorothe Burggraf, Helge K Martens, Gabriele Jager, Gerhard F HamannAbstract:While recombinant tissue plasminogen activator (rt-PA) is successfully used in human ischemic stroke, it may also cause hemorrhagic complications. Animal experiments have shown that hemorrhages are related to microvascular Basal Lamina damage.We investigated the effects of different doses of rt-PA on the brain microvasculature. Experimental cerebral ischemia in rats was induced for 3 h and followed by 24 h reperfusion (suture model). Each group of rats (n = 6) received either treatment (0.9, 9, or 18 mg rt-PA/kg body weight) or saline (control group) at the end of ischemia. The loss of microvascular Basal Lamina antigen collagen type IV was measured by Western blot of the ischemic and non-ischemic Basal ganglia and cortex. Compared with the contralateral non-ischemic area, collagen type IV was significantly reduced in the ischemic area: (Basal ganglia/cortex) 43% +/- 9% / 64% +/- 4 %. Low/moderate doses of rt-PA had a protective effect: 0.9 mg 79% +/- 3% / 89% +/- 6%, 9 mg 72% +/- 9%/ 81% +/- 12% (p < 0.05). Higher doses of rt-PA (18 mg) had a similar effect as seen in untreated controls: 57% +/- 11% / 59% +/- 9% (p < 0.05,Anova). MMP-9 and MMP- 2, measured by gelatine zymography, steadily increased over higher doses of rt-PA: MMP-9 (Basal ganglia/cortex): control 115% +/- 4% / 123% +/- 3% compared with 18 mg rt-PA 146% +/- 5%/ 162% +/- 6% (p < 0.05) and MMP-2: control 109% +/- 4%/ 116% +/- 5% and 18 mg rt-PA 222% +/- 15%/ 252% +/- 2% (p < 0.05). Low to moderate doses of rt-PA protect the microvascular Basal Lamina, whereas high doses of rt-PA have the opposite effect, probably due to increased coactivation of MMP-2 and MMP-9.
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microvascular Basal Lamina injury after experimental focal cerebral ischemia and reperfusion in the rat
Journal of Cerebral Blood Flow and Metabolism, 2002Co-Authors: Gerhard F Hamann, Dorothe Burggraf, Helge K Martens, Gabriele Jager, Martin Liebetrau, Christian U A Kloss, G Bultemeier, Natalie Wunderlich, Thomas PfefferkornAbstract:To define the location and extent of microvascular damage of the Basal Lamina after cerebral ischemia and reperfusion in rats, the authors subjected animals (n = 16) to 3 hours of focal cerebral ischemia and 24 hours of reperfusion using the suture middle cerebral artery occlusion model; sham-operated animals served as controls (n = 6). The Western blot technique was used to define the collagen type IV protein content in various brain regions, whereas immunohistochemistry identified microvascular Basal Lamina loss (anticollagen type IV staining). The extent of damage was quantified by automatic morphometric video-imaging analysis. Statistical analysis was based on the Mann-Whitney test and the paired Student's t-test. The ischemic hemisphere showed a reduction of the collagen type IV protein content after ischemia and reperfusion in the Western blot (reduction compared with the nonischemic side: total hemisphere, 33% +/- 6%; Basal ganglia, 25% +/- 7%; cortex 49% +/- 4%; P < 0.01) [corrected]. There was also a decrease in the number of cerebral microvessels between the ischemic and nonischemic hemispheres (20% +/- 2%), cortical (8% +/- 3%), and Basal ganglia areas (31% +/- 3%) (P < 0.001). Besides a reduction of the vessel number, there was also a loss in Basal Lamina antigen-positive stained area in ischemic areas (hemisphere, 16% +/- 3%; cortex, 14% +/- 3%; Basal ganglia, 21% +/- 4%; P < 0.01) [corrected]. Cortical areas had a less pronounced Basal Lamina loss than Basal ganglia (P < 0.05). For the first time, microvascular Basal Lamina damage, indicated by collagen type IV loss, is proven in rats by biochemical and morphometric analysis. These changes are comparable with those found in nonhuman primates. The authors report novel data regarding microvascular ischemic changes in the cortex. These data provide a basis for future experiments to determine the mechanisms of ischemic microvascular damage and to devise new therapeutic strategies.
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microvascular Basal Lamina injury after experimental focal cerebral ischemia and reperfusion in the rat
Journal of Cerebral Blood Flow and Metabolism, 2002Co-Authors: Gerhard F Hamann, Dorothe Burggraf, Helge K Martens, Gabriele Jager, Martin Liebetrau, Christian U A Kloss, G Bultemeier, Natalie Wunderlich, Thomas PfefferkornAbstract:To define the location and extent of microvascular damage of the Basal Lamina after cerebral ischemia and reperfusion in rats, the authors subjected animals (n = 16) to 3 hours of focal cerebral ischemia and 24 hours of reperfusion using the suture middle cerebral artery occlusion model; sham-operated animals served as controls (n = 6). The Western blot technique was used to define the collagen type IV protein content in various brain regions, whereas immunohistochemistry identified microvascular Basal Lamina loss (anticollagen type IV staining). The extent of damage was quantified by automatic morphometric video-imaging analysis. Statistical analysis was based on the Mann-Whitney test and the paired Student's t-test. The ischemic hemisphere showed a reduction of the collagen type IV protein content after ischemia and reperfusion in the Western blot (reduction compared with the nonischemic side: total hemisphere, 33% ± 6%; Basal ganglia, 49% ± 4%; cortex, 25% ± 7%; P < 0.01). There was also a decrease in ...
