The Experts below are selected from a list of 936 Experts worldwide ranked by ideXlab platform
James D Schmelzer - One of the best experts on this subject based on the ideXlab platform.
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enhanced inflammatory response via activation of nf κb in acute experimental diabetic neuropathy subjected to ischemia reperfusion injury
Journal of the Neurological Sciences, 2006Co-Authors: Yanping Wang, Ann M Schmeichel, Haruyasu Iida, James D Schmelzer, Phillip A LowAbstract:Reperfusion following ischemia increases ischemic fiber degeneration (IFD) in diabetic nerves compared to control normoglycemic nerves. The mechanism of this excessive susceptibility is unclear. Since reperfusion injury results in an inflammatory response, we tested the hypothesis that the diabetic state increases the inflammatory cascade. We used an animal model of unilateral ischemia-reperfusion (IR) injury to streptozotocin (STZ)-induced diabetic nerve to evaluate the density and localization of mediators of the inflammatory response using selective immunolabeling methods (for nuclear factor kappa B (NF-kappaB), intercellular adhesion molecule-1 (ICAM-1), cytokines and inflammatory cells). We studied a 1-month diabetic group and an age-matched control group (n=6 each). The right limb underwent 3 h ischemia at 35 degrees C and 7 days reperfusion. This was achieved by ligating the supplying arteries and collaterals to the right sciatic-tibial nerve for 3 h, followed by releasing the ties. Immunohistochemistry was performed on proximal sciatic and mid tibial nerves. NF-kappaB expression in diabetic sciatic endothelial cell and Schwann cell (SC) was significantly increased over that of controls subjected to identical IR injury. We observed a nearly 2-fold increase in density of NF-kappaB and ICAM-1 expression in microvessels of diabetic nerve compared with control nerve. Extensive infiltration of monocyte macrophages (1C7) was observed in the Endoneurium of diabetic nerves, while only mild infiltration of granulocytes (HIS 48) occurred in the Endoneurium of diabetic tibial nerves. This study provides evidence for an enhanced inflammatory response in diabetic nerves subjected to IR injury apparently via NF-kappaB activation.
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enhanced inflammatory response via activation of nf κb in acute experimental diabetic neuropathy subjected to ischemia reperfusion injury
Journal of the Neurological Sciences, 2006Co-Authors: Yanping Wang, Ann M Schmeichel, Haruyasu Iida, James D SchmelzerAbstract:Abstract Reperfusion following ischemia increases ischemic fiber degeneration (IFD) in diabetic nerves compared to control normoglycemic nerves. The mechanism of this excessive susceptibility is unclear. Since reperfusion injury results in an inflammatory response, we tested the hypothesis that the diabetic state increases the inflammatory cascade. We used an animal model of unilateral ischemia–reperfusion (IR) injury to streptozotocin (STZ)-induced diabetic nerve to evaluate the density and localization of mediators of the inflammatory response using selective immunolabeling methods (for nuclear factor kappa B (NF-κB), intercellular adhesion molecule-1 (ICAM-1), cytokines and inflammatory cells). We studied a 1-month diabetic group and an age-matched control group (n = 6 each). The right limb underwent 3 h ischemia at 35 °C and 7 days reperfusion. This was achieved by ligating the supplying arteries and collaterals to the right sciatic–tibial nerve for 3 h, followed by releasing the ties. Immunohistochemistry was performed on proximal sciatic and mid tibial nerves. NF-κB expression in diabetic sciatic endothelial cell and Schwann cell (SC) was significantly increased over that of controls subjected to identical IR injury. We observed a nearly 2-fold increase in density of NF-κB and ICAM-1 expression in microvessels of diabetic nerve compared with control nerve. Extensive infiltration of monocyte macrophages (1C7) was observed in the Endoneurium of diabetic nerves, while only mild infiltration of granulocytes (HIS 48) occurred in the Endoneurium of diabetic tibial nerves. This study provides evidence for an enhanced inflammatory response in diabetic nerves subjected to IR injury apparently via NF-κB activation.
Yanping Wang - One of the best experts on this subject based on the ideXlab platform.
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enhanced inflammatory response via activation of nf κb in acute experimental diabetic neuropathy subjected to ischemia reperfusion injury
Journal of the Neurological Sciences, 2006Co-Authors: Yanping Wang, Ann M Schmeichel, Haruyasu Iida, James D Schmelzer, Phillip A LowAbstract:Reperfusion following ischemia increases ischemic fiber degeneration (IFD) in diabetic nerves compared to control normoglycemic nerves. The mechanism of this excessive susceptibility is unclear. Since reperfusion injury results in an inflammatory response, we tested the hypothesis that the diabetic state increases the inflammatory cascade. We used an animal model of unilateral ischemia-reperfusion (IR) injury to streptozotocin (STZ)-induced diabetic nerve to evaluate the density and localization of mediators of the inflammatory response using selective immunolabeling methods (for nuclear factor kappa B (NF-kappaB), intercellular adhesion molecule-1 (ICAM-1), cytokines and inflammatory cells). We studied a 1-month diabetic group and an age-matched control group (n=6 each). The right limb underwent 3 h ischemia at 35 degrees C and 7 days reperfusion. This was achieved by ligating the supplying arteries and collaterals to the right sciatic-tibial nerve for 3 h, followed by releasing the ties. Immunohistochemistry was performed on proximal sciatic and mid tibial nerves. NF-kappaB expression in diabetic sciatic endothelial cell and Schwann cell (SC) was significantly increased over that of controls subjected to identical IR injury. We observed a nearly 2-fold increase in density of NF-kappaB and ICAM-1 expression in microvessels of diabetic nerve compared with control nerve. Extensive infiltration of monocyte macrophages (1C7) was observed in the Endoneurium of diabetic nerves, while only mild infiltration of granulocytes (HIS 48) occurred in the Endoneurium of diabetic tibial nerves. This study provides evidence for an enhanced inflammatory response in diabetic nerves subjected to IR injury apparently via NF-kappaB activation.
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enhanced inflammatory response via activation of nf κb in acute experimental diabetic neuropathy subjected to ischemia reperfusion injury
Journal of the Neurological Sciences, 2006Co-Authors: Yanping Wang, Ann M Schmeichel, Haruyasu Iida, James D SchmelzerAbstract:Abstract Reperfusion following ischemia increases ischemic fiber degeneration (IFD) in diabetic nerves compared to control normoglycemic nerves. The mechanism of this excessive susceptibility is unclear. Since reperfusion injury results in an inflammatory response, we tested the hypothesis that the diabetic state increases the inflammatory cascade. We used an animal model of unilateral ischemia–reperfusion (IR) injury to streptozotocin (STZ)-induced diabetic nerve to evaluate the density and localization of mediators of the inflammatory response using selective immunolabeling methods (for nuclear factor kappa B (NF-κB), intercellular adhesion molecule-1 (ICAM-1), cytokines and inflammatory cells). We studied a 1-month diabetic group and an age-matched control group (n = 6 each). The right limb underwent 3 h ischemia at 35 °C and 7 days reperfusion. This was achieved by ligating the supplying arteries and collaterals to the right sciatic–tibial nerve for 3 h, followed by releasing the ties. Immunohistochemistry was performed on proximal sciatic and mid tibial nerves. NF-κB expression in diabetic sciatic endothelial cell and Schwann cell (SC) was significantly increased over that of controls subjected to identical IR injury. We observed a nearly 2-fold increase in density of NF-κB and ICAM-1 expression in microvessels of diabetic nerve compared with control nerve. Extensive infiltration of monocyte macrophages (1C7) was observed in the Endoneurium of diabetic nerves, while only mild infiltration of granulocytes (HIS 48) occurred in the Endoneurium of diabetic tibial nerves. This study provides evidence for an enhanced inflammatory response in diabetic nerves subjected to IR injury apparently via NF-κB activation.
Bernd C Kieseier - One of the best experts on this subject based on the ideXlab platform.
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trapped in the epineurium early entry into the Endoneurium is restricted to neuritogenic t cells in experimental autoimmune neuritis
Journal of Neuroinflammation, 2018Co-Authors: Anne K Mausberg, Fabian Szepanowski, Francesca Odoardi, Alexander Flugel, Christoph Kleinschnitz, Mark Stettner, Bernd C KieseierAbstract:Autoimmune polyneuropathies are acquired inflammatory disorders of the peripheral nervous system (PNS) characterized by inflammation, demyelination, and axonal degeneration. Although the pathogenesis has not been fully elucidated, T cells recognizing self-antigens are believed to initiate inflammation in a subgroup of patients. However, the route and time of T cell entry into the PNS have not yet been described in detail. In this study, we analyzed both kinetics as well as localization of retrovirally transfected green fluorescent protein (GFP)-expressing neuritogenic T lymphocytes in experimental autoimmune neuritis (EAN). T lymphocytes obtained from rats following EAN induction by immunization with peripheral nerve protein peptide P255–78 were retrovirally engineered to express GFP. Non-specific T cells were negatively selected by in vitro restimulation, whereas GFP-expressing neuritogenic T cells (reactive to P255–78) were adoptively transferred into healthy rats (AT-EAN). Antigen-specific T cell tracking and localization was performed by flow cytometry and immunohistochemistry during the course of disease. After induction of autoimmune neuritis, P2-reactive T cells were detectable in the liver, spleen, lymph nodes, lung, peripheral blood, and the sciatic nerves with distinct kinetics. A significant number of GFP+ T cells appeared early in the lung with a peak at day four. In the peripheral nerves within the first days, GFP-negative T cells rapidly accumulated and exceeded the number of GFP-expressing cells, but did not enter the Endoneurium. Very early after adoptive transfer, T cells are found in proximity to peripheral nerves and in the epineurium. However, only GFP-expressing neuritogenic T cells are able to enter the Endoneurium from day five after transfer. Our findings suggest that neuritogenic T cells invade the PNS early in the course of disease. However, neuritogenic T cells cross the blood-nerve barrier with a certain delay without preference to dorsal roots. Further understanding of the pathophysiological role of autoagressive T cells may help to improve therapeutic strategies in immune-mediated neuropathies.
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Trapped in the epineurium: early entry into the Endoneurium is restricted to neuritogenic T cells in experimental autoimmune neuritis
'Springer Science and Business Media LLC', 2018Co-Authors: Anne K Mausberg, Fabian Szepanowski, Francesca Odoardi, Alexander Flugel, Christoph Kleinschnitz, Mark Stettner, Bernd C KieseierAbstract:Abstract Background Autoimmune polyneuropathies are acquired inflammatory disorders of the peripheral nervous system (PNS) characterized by inflammation, demyelination, and axonal degeneration. Although the pathogenesis has not been fully elucidated, T cells recognizing self-antigens are believed to initiate inflammation in a subgroup of patients. However, the route and time of T cell entry into the PNS have not yet been described in detail. In this study, we analyzed both kinetics as well as localization of retrovirally transfected green fluorescent protein (GFP)-expressing neuritogenic T lymphocytes in experimental autoimmune neuritis (EAN). Methods T lymphocytes obtained from rats following EAN induction by immunization with peripheral nerve protein peptide P255–78 were retrovirally engineered to express GFP. Non-specific T cells were negatively selected by in vitro restimulation, whereas GFP-expressing neuritogenic T cells (reactive to P255–78) were adoptively transferred into healthy rats (AT-EAN). Antigen-specific T cell tracking and localization was performed by flow cytometry and immunohistochemistry during the course of disease. Results After induction of autoimmune neuritis, P2-reactive T cells were detectable in the liver, spleen, lymph nodes, lung, peripheral blood, and the sciatic nerves with distinct kinetics. A significant number of GFP+ T cells appeared early in the lung with a peak at day four. In the peripheral nerves within the first days, GFP-negative T cells rapidly accumulated and exceeded the number of GFP-expressing cells, but did not enter the Endoneurium. Very early after adoptive transfer, T cells are found in proximity to peripheral nerves and in the epineurium. However, only GFP-expressing neuritogenic T cells are able to enter the Endoneurium from day five after transfer. Conclusions Our findings suggest that neuritogenic T cells invade the PNS early in the course of disease. However, neuritogenic T cells cross the blood-nerve barrier with a certain delay without preference to dorsal roots. Further understanding of the pathophysiological role of autoagressive T cells may help to improve therapeutic strategies in immune-mediated neuropathies
Phillip A Low - One of the best experts on this subject based on the ideXlab platform.
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enhanced inflammatory response via activation of nf κb in acute experimental diabetic neuropathy subjected to ischemia reperfusion injury
Journal of the Neurological Sciences, 2006Co-Authors: Yanping Wang, Ann M Schmeichel, Haruyasu Iida, James D Schmelzer, Phillip A LowAbstract:Reperfusion following ischemia increases ischemic fiber degeneration (IFD) in diabetic nerves compared to control normoglycemic nerves. The mechanism of this excessive susceptibility is unclear. Since reperfusion injury results in an inflammatory response, we tested the hypothesis that the diabetic state increases the inflammatory cascade. We used an animal model of unilateral ischemia-reperfusion (IR) injury to streptozotocin (STZ)-induced diabetic nerve to evaluate the density and localization of mediators of the inflammatory response using selective immunolabeling methods (for nuclear factor kappa B (NF-kappaB), intercellular adhesion molecule-1 (ICAM-1), cytokines and inflammatory cells). We studied a 1-month diabetic group and an age-matched control group (n=6 each). The right limb underwent 3 h ischemia at 35 degrees C and 7 days reperfusion. This was achieved by ligating the supplying arteries and collaterals to the right sciatic-tibial nerve for 3 h, followed by releasing the ties. Immunohistochemistry was performed on proximal sciatic and mid tibial nerves. NF-kappaB expression in diabetic sciatic endothelial cell and Schwann cell (SC) was significantly increased over that of controls subjected to identical IR injury. We observed a nearly 2-fold increase in density of NF-kappaB and ICAM-1 expression in microvessels of diabetic nerve compared with control nerve. Extensive infiltration of monocyte macrophages (1C7) was observed in the Endoneurium of diabetic nerves, while only mild infiltration of granulocytes (HIS 48) occurred in the Endoneurium of diabetic tibial nerves. This study provides evidence for an enhanced inflammatory response in diabetic nerves subjected to IR injury apparently via NF-kappaB activation.
David Muir - One of the best experts on this subject based on the ideXlab platform.
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chondroitinase c selectively degrades chondroitin sulfate glycosaminoglycans that inhibit axonal growth within the Endoneurium of peripheral nerve
PLOS ONE, 2016Co-Authors: J Graham, David MuirAbstract:The success of peripheral nerve regeneration is highly dependent on the regrowth of axons within the endoneurial basal lamina tubes that promote target-oriented pathfinding and appropriate reinnervation. Restoration of nerve continuity at this structural level after nerve transection injury by direct repair and nerve grafting remains a major surgical challenge. Recently, biological approaches that alter the balance of growth inhibitors and promoters in nerve have shown promise to improve appropriate axonal regeneration and recovery of peripheral nerve function. Chondroitin sulfate proteoglycans (CSPGs) are known inhibitors of axonal growth. This growth inhibition is mainly associated with a CSPG's glycosaminoglycan chains. Enzymatic degradation of these chains with chondroitinase eliminates this inhibitory activity and, when applied in vivo, can improve the outcome of nerve repair. To date, these encouraging findings were obtained with chondroitinase ABC (a pan-specific chondroitinase). The aim of this study was to examine the distribution of CSPG subtypes in rodent, rabbit, and human peripheral nerve and to test more selective biological enzymatic approaches to improve appropriate axonal growth within the Endoneurium and minimize aberrant growth. Here we provide evidence that the Endoneurium, but not the surrounding epineurium, is rich in CSPGs that have glycosaminoglycan chains readily degraded by chondroitinase C. Biochemical studies indicate that chondroitinase C has degradation specificity for 6-sulfated glycosaminoglycans found in peripheral nerve. We found that chondroitinase C degrades and inactivates inhibitory CSPGs within the Endoneurium but not so much in the surrounding nerve compartments. Cryoculture bioassays (neurons grown on tissue sections) show that chondroitinase C selectively and significantly enhanced neuritic growth associated with the endoneurial basal laminae without changing growth-inhibiting properties of the surrounding epineurium. Interestingly, chondroitinase ABC treatment increased greatly the growth-promoting properties of the epineurial tissue whereas chondroitinase C had little effect. Our evidence indicates that chondroitinase C effectively degrades and inactivates inhibitory CSPGs present in the endoneurial Schwann cell basal lamina and does so more specifically than chondroitinase ABC. These findings are discussed in the context of improving nerve repair and regeneration and the growth-promoting properties of processed nerve allografts.
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Endoneurial distribution of ΔCS-A and ΔCS-C relative to laminin in normal rat peripheral nerve.
2016Co-Authors: James B. Graham, David MuirAbstract:Normal rat sciatic nerve was subjected to chondroitinase ABC treatment and double immunolabeled with antibodies against laminin-1 and either ΔCS-A (C4S antibody) or ΔCS-C (C6S antibody). (A) C4S immunolabeling was present within the Endoneurium but appeared to be isolated to the outside of the endoneurial tubes and seemed to be absent from the perineurium. (B) Immunolabeling for laminin revealed ring-like structures within the Endoneurium that represent the boundaries of basal lamina tubes. Laminin was also present within the perineurium. (C) Combining both (A) and (B) provided a complementary pattern where the C4S (Red) immunoreactive areas were distinct and separate from the laminin (Green) immunoreactive rings of the basal lamina tubes. (D) C6S immunolabeling revealed a pattern that more resembled the ring-like laminin structures of the basal lamina (E). (F) Combining both (D) and (E) confirms that both components colocalize to the basal lamina tubes of the Endoneurium. Scale bar: 20 μm.
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Perlecan distribution relative to laminin, ΔCS-A, and ΔCS-C in normal rat peripheral nerve.
2016Co-Authors: James B. Graham, David MuirAbstract:Normal rat sciatic nerve was subjected to chondroitinase ABC treatment and immunolabeled with antibodies against perlecan and laminin or ΔCS-C or ΔCS-A. (A) Perlecan was present within the Endoneurium tubes and appeared to label the ring-like structures in a similar pattern to laminin (B). (C) Combination of filters revealed that both laminin and perlecan closely associate within the basal lamina tubes. (D) Perlecan also closely associated with ΔCS-C tubes (E) which was confirmed when filters were merged (F). (G) Perlecan did not colocalize with ΔCS-A (H) within the Endoneurium and the combination of both filters clearly demonstrated a complementary distribution (I). Scale bar: 20 μm.
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Distribution of proteoglycans relative to laminin in normal rat and rabbit peripheral nerve.
2016Co-Authors: James B. Graham, David MuirAbstract:Normal rat (A and B) and rabbit (C,D,E,F) sciatic nerve was subjected to immunohistochemical analysis with antibodies against laminin-2 (A), proteoglycan core proteins (B,C,D) and glycosaminoglycan chains (E and F). (A) Laminin was found within the nerve Endoneurium and perineurium while only present within the basement membranes of blood vessels in the epineurium. (B) The heparan sulfate/chondroitin sulfate proteoglycan, perlecan, colocalized with laminin. (C) The chondroitin sulfate/dermatan sulfate proteoglycan, decorin, appeared primarily within the perineurium with faint immunoreactivity found amongst a subset of endoneurial tubes. (D) Versican (12C5) had a similar distribution to decorin primarily within the perineurium and faintly dispersed amongst a subset of endoneurial tubes. (E) A commonly used marker for chondroitin sulfate glycosaminoglycans, antibody CS-56, was mostly found within the Endoneurium and appeared to label some components of the epineurium. (F) 473-HD, which has been reported to be specific for chondroitin sulfate/dermatan sulfate hybrid glycosaminoglycan chains, produced a similar staining pattern as decorin and versican. Scale bar: 100 μm.
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Chondroitinase C effectively removed endoneurial chondroitin sulfate glycosaminoglycans.
2016Co-Authors: James B. Graham, David MuirAbstract:Normal human (A and C) and normal rabbit (B and D) were treated with chondroitinase C (C and D) and immunolabeled for CS-56 (A and C) or 473-HD (B and D). (A) CS-56 was present throughout the normal human nerve Endoneurium. (B) 473-HD immunolabeled a subset of endoneurial basal laminae tubes within the rabbit nerve. Chondroitinase C treatment effectively removed immunoreactivity of both CS-56 (C) and 473-HD (D) antibodies which indicated the glycosaminoglycan chains were cleaved off the core protein. Scale bar: 100μm.