The Experts below are selected from a list of 981 Experts worldwide ranked by ideXlab platform
D I Graham - One of the best experts on this subject based on the ideXlab platform.
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freeze fracture and cytochemical evidence for structural and functional alteration in the Axolemma and myelin sheath of adult guinea pig optic nerve fibers after stretch injury
Journal of Neurotrauma, 1999Co-Authors: W L Maxwell, Rachian Kosanlavit, Brian J Mccreath, Owen Reid, D I GrahamAbstract:ABSTRACT Recent work in animal models of human diffuse axonal injury has generated the hypothesis that, rather than there being physical disruption of the Axolemma at the time of injury, a pertubation of the membrane occurs, which leads, over time, to a dysfunction of the physiology of the Axolemmal. This dysfunction is posited to lead to a disruption of ionic homeostasis within the injured axon, leading to secondary axotomy some hours after the initial insult. We decided to test the hypothesis that membrane pump/ion channel activity or function is compromised and this would be reflected in structural changes within the Axolemma and myelin sheath. We used freeze fracture and cytochemical techniques to provide evidence for change in membrane structure and the activity of membrane pumps after nondisruptive axonal injury in the adult guinea pig optic nerve. Within 10 min of injury, structural changes occurred in the distribution and number of intramembranous particles (IMPs) in the internodal Axolemma. By 4 ...
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loss of axonal microtubules and neurofilaments after stretch injury to guinea pig optic nerve fibers
Journal of Neurotrauma, 1997Co-Authors: W L Maxwell, D I GrahamAbstract:Axonal swellings, characterized by focal accumulations of membranous organelles at presumed sites of interrupted axonal transport, occur in diffuse axonal injury (DAI) in human, blunt head injury and in animal models of nondisruptive axonal injury. Membranous organelles are transported by fast axonal transport in association with microtubules. Although loss of microtubules has been documented at levels of injury severe enough to result in permeabilization of the Axolemma to tracers such as horseradish peroxidase, there has been no detailed analysis of responses by microtubules in less severe or milder forms of nondisruptive axonal injury. To test the hypothesis that in less severe forms of axonal injury there is a rapid response by axonal microtubules that might provide an explanation for loss of fast axonal transport, we have carried out a morphometric analysis of microtubules in CNS axons after stretch-injury. There is loss of microtubules at nodes of Ranvier with nodal blebs within 15 min of injury, and in internodal axonal swellings between 2 and 4 h. There is a return to control values at nodes of Ranvier by 4 h, and at the internode by 24 h. There is no loss of microtubules at paranodes, although there is a reduction in their density in the first 2 h after injury. The greatest loss of microtubules occurs at sites of Axolemma infolding. Hypothetical mechanisms that might lead to this loss resulting in focal disruption of fast axonal transport and the formation of axonal swellings are discussed.
Maarten H P Kole - One of the best experts on this subject based on the ideXlab platform.
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saltatory conduction along myelinated axons involves a periaxonal nanocircuit
Cell, 2020Co-Authors: Charles C H Cohen, Marko A Popovic, Jan Klooster, Marietheres Weil, Wiebke Mobius, Maarten H P Kole, Klaus-armin NaveAbstract:The propagation of electrical impulses along axons is highly accelerated by the myelin sheath and produces saltating or "jumping" action potentials across internodes, from one node of Ranvier to the next. The underlying electrical circuit, as well as the existence and role of submyelin conduction in saltatory conduction remain, however, elusive. Here, we made patch-clamp and high-speed voltage-calibrated optical recordings of potentials across the nodal and internodal Axolemma of myelinated neocortical pyramidal axons combined with electron microscopy and experimentally constrained cable modeling. Our results reveal a nanoscale yet conductive periaxonal space, incompletely sealed at the paranodes, which separates the potentials across the low-capacitance myelin sheath and internodal Axolemma. The emerging double-cable model reproduces the recorded evolution of voltage waveforms across nodes and internodes, including rapid nodal potentials traveling in advance of attenuated waves in the internodal Axolemma, revealing a mechanism for saltation across time and space.
A B Oestreicher - One of the best experts on this subject based on the ideXlab platform.
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ultrastructural co localization of calmodulin and b 50 growth associated protein 43 at the plasma membrane of proximal unmyelinated axon shafts studied in the model of the regenerating rat sciatic nerve
Neuroscience, 1997Co-Authors: Paul Verkade, L H Schrama, A J Verkleij, W H Gispen, A B OestreicherAbstract:Calmodulin and de-phosphorylated B-50/growth-associated protein-43 (GAP-43) have been shown to bind in vitro in a molecular complex, but evidence for an in situ association in the nervous system does not exist. Previously, we have reported that, in the model of the regenerating rat sciatic nerve, the B-50/GAP-43 immunoreactivity is increased and concentrated at the Axolemma of unmyelinated axons located proximal to the site of injury and axon outgrowth. To explore a putative function of B-50/GAP-43, namely, the capacity of binding calmodulin to the plasma membrane, we examined the ultrastructural distribution of calmodulin in the proximal unmyelinated axon shafts of this model, using double immunolabelling and detection by fluorescent or gold probes conjugated to second antibodies. Immunofluorescence showed that seven days post-sciatic nerve crush the calmodulin immunoreactivity, similar to B-50/GAP-43 immunoreactivity, was intense in unmyelinated axon shafts located proximal to the site of injury of the regenerating nerve. Ultrastructurally, calmodulin was located at the Axolemma of these regenerating unmyelinated axon shafts and inside the axoplasm, where it was associated with vesicles and microtubules. The plasma membrane labelling (approximately 69%) was significantly higher than the axoplasmic labelling. Over 60% of the plasma membrane-associated calmodulin co-localized with B-50/GAP-43 in a non-random distribution. Since normally calmodulin is largely present in the cytoplasm, these data suggest that calmodulin has been concentrated at the plasma membrane of unmyelinated axons, most probably by B-50/GAP-43. If the concentrating effect is due to B-50/GAP-43, then there is a possibility that these proteins may be present as a molecular complex in situ. The physiological significance could be that this association regulates the local availability of both B-50/GAP-43 and calmodulin for other interactions.
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the increase in b 50 gap 43 in regenerating rat sciatic nerve occurs predominantly in unmyelinated axon shafts a quantitative ultrastructural study
The Journal of Comparative Neurology, 1995Co-Authors: Paul Verkade, A J Verkleij, A B Oestreicher, W H GispenAbstract:The growth-associated protein B-50/GAP-43 is thought to play a crucial role in axonal growth. We investigated, by quantitative immunoelectron microscopy, whether there are differences in the subcellular distribution of B-50 in unmyelinated and myelinated axons of intact and regenerating sciatic nerves. Adult rats received an unilateral sciatic nerve crush and were euthanized 8 days later. Nerve pieces proximal from the crush site were embedded, and B-50 was visualized by specific B-50 antibodies and immunogold detection in ultrathin sections. The density of B-50 at the plasma membrane of unmyelinated axon shafts was significantly increased in the ipsilateral regenerating nerve in comparison to that of the contralateral intact nerve. In contrast, there was no significant difference in the B-50 density at the Axolemma of myelinated regenerating and intact axon shafts. In the contralateral intact nerve, more B-50 was associated with the Axolemma of unmyelinated axons than with the plasma membrane of myelinated axons. The density of axoplasmic B-50 was similar in intact unmyelinated and myelinated axon shafts, but was higher in regenerating nerve than in intact nerve. This suggests that enhanced axonal transport of B-50 occurs during axon outgrowth. Our study demonstrates a differential subcellular distribution of B-50 in unmyelinated and myelinated axon shafts in both the intact and regenerating sciatic nerve, indicating a differential inducible capacity for remodeling of the axon shafts.
W L Maxwell - One of the best experts on this subject based on the ideXlab platform.
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freeze fracture and cytochemical evidence for structural and functional alteration in the Axolemma and myelin sheath of adult guinea pig optic nerve fibers after stretch injury
Journal of Neurotrauma, 1999Co-Authors: W L Maxwell, Rachian Kosanlavit, Brian J Mccreath, Owen Reid, D I GrahamAbstract:ABSTRACT Recent work in animal models of human diffuse axonal injury has generated the hypothesis that, rather than there being physical disruption of the Axolemma at the time of injury, a pertubation of the membrane occurs, which leads, over time, to a dysfunction of the physiology of the Axolemmal. This dysfunction is posited to lead to a disruption of ionic homeostasis within the injured axon, leading to secondary axotomy some hours after the initial insult. We decided to test the hypothesis that membrane pump/ion channel activity or function is compromised and this would be reflected in structural changes within the Axolemma and myelin sheath. We used freeze fracture and cytochemical techniques to provide evidence for change in membrane structure and the activity of membrane pumps after nondisruptive axonal injury in the adult guinea pig optic nerve. Within 10 min of injury, structural changes occurred in the distribution and number of intramembranous particles (IMPs) in the internodal Axolemma. By 4 ...
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loss of axonal microtubules and neurofilaments after stretch injury to guinea pig optic nerve fibers
Journal of Neurotrauma, 1997Co-Authors: W L Maxwell, D I GrahamAbstract:Axonal swellings, characterized by focal accumulations of membranous organelles at presumed sites of interrupted axonal transport, occur in diffuse axonal injury (DAI) in human, blunt head injury and in animal models of nondisruptive axonal injury. Membranous organelles are transported by fast axonal transport in association with microtubules. Although loss of microtubules has been documented at levels of injury severe enough to result in permeabilization of the Axolemma to tracers such as horseradish peroxidase, there has been no detailed analysis of responses by microtubules in less severe or milder forms of nondisruptive axonal injury. To test the hypothesis that in less severe forms of axonal injury there is a rapid response by axonal microtubules that might provide an explanation for loss of fast axonal transport, we have carried out a morphometric analysis of microtubules in CNS axons after stretch-injury. There is loss of microtubules at nodes of Ranvier with nodal blebs within 15 min of injury, and in internodal axonal swellings between 2 and 4 h. There is a return to control values at nodes of Ranvier by 4 h, and at the internode by 24 h. There is no loss of microtubules at paranodes, although there is a reduction in their density in the first 2 h after injury. The greatest loss of microtubules occurs at sites of Axolemma infolding. Hypothetical mechanisms that might lead to this loss resulting in focal disruption of fast axonal transport and the formation of axonal swellings are discussed.
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cytochemical evidence for redistribution of membrane pump calcium atpase and ecto ca atpase activity and calcium influx in myelinated nerve fibres of the optic nerve after stretch injury
Journal of Neurocytology, 1995Co-Authors: W L Maxwell, B J Mccreath, D I Graham, Thomas A GennarelliAbstract:There has been controversy for some time as to whether a posttraumatic influx of calcium ions occurs in stretch/non-disruptively injured axons within the central nervous system in both human diffuse axonal injury and a variety of models of such injury. We have used the oxalate/pyroantimonate technique to provide cytochemical evidence in support of such an ionic influx after focal axonal injury to normoxic guinea pig optic nerve axons, a model for human diffuse axonal injury. We present evidence for morphological changes within 15 min of injury where aggregates of pyroantimonate precipitate occur in nodal blebs at nodes of Ranvier, in focal swellings within axonal mitochondria, and at localized sites of separation of myelin lamellae. In parallel with these studies, we have used cytochemical techniques for localization of membrane pump Ca2+-ATPase and ecto-Ca-ATPase activity. There is loss of labelling for membrane pump Ca2+-ATPase activity on the nodal Axolemma, together with loss of ecto-Ca-ATPase from the external aspect of the myelin sheath at sites of focal separation of myelin lamellae. Disruption of myelin lamellae and loss of ecto-Ca-ATPase activity becomes widespread between 1 and 4 h after injury. This is correlated with both infolding and retraction of the Axolemma from the internal aspect of the myelin sheath to form periaxonal spaces which are characterized by aggregates of pyroantimonate precipitate, and the development of myelin intrusions into invaginations of the Axolemma such that the regular profile of the axon is lost. There is novel labelling of membrane pump Ca2+-ATPase on the cytoplasmic aspect of the internodal Axolemma between 1 and 4 h after injury. There is loss of an organized axonal cytoskeleton in a proportion of nerve fibres by 4–6 h after injury. We suggest that these changes demonstrate a progressive pathology linked to calcium ion influx after stretch (non-disruptive) axonal injury to optic nerve myelinated fibres. We posit that calcium influx, linked to or correlated with changes in Ca2+-ATPase activities, results in dissolution of the axonal cytoskeleton and axotomy between 4 and 6 h after the initial insult to axons.
Paul Verkade - One of the best experts on this subject based on the ideXlab platform.
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ultrastructural co localization of calmodulin and b 50 growth associated protein 43 at the plasma membrane of proximal unmyelinated axon shafts studied in the model of the regenerating rat sciatic nerve
Neuroscience, 1997Co-Authors: Paul Verkade, L H Schrama, A J Verkleij, W H Gispen, A B OestreicherAbstract:Calmodulin and de-phosphorylated B-50/growth-associated protein-43 (GAP-43) have been shown to bind in vitro in a molecular complex, but evidence for an in situ association in the nervous system does not exist. Previously, we have reported that, in the model of the regenerating rat sciatic nerve, the B-50/GAP-43 immunoreactivity is increased and concentrated at the Axolemma of unmyelinated axons located proximal to the site of injury and axon outgrowth. To explore a putative function of B-50/GAP-43, namely, the capacity of binding calmodulin to the plasma membrane, we examined the ultrastructural distribution of calmodulin in the proximal unmyelinated axon shafts of this model, using double immunolabelling and detection by fluorescent or gold probes conjugated to second antibodies. Immunofluorescence showed that seven days post-sciatic nerve crush the calmodulin immunoreactivity, similar to B-50/GAP-43 immunoreactivity, was intense in unmyelinated axon shafts located proximal to the site of injury of the regenerating nerve. Ultrastructurally, calmodulin was located at the Axolemma of these regenerating unmyelinated axon shafts and inside the axoplasm, where it was associated with vesicles and microtubules. The plasma membrane labelling (approximately 69%) was significantly higher than the axoplasmic labelling. Over 60% of the plasma membrane-associated calmodulin co-localized with B-50/GAP-43 in a non-random distribution. Since normally calmodulin is largely present in the cytoplasm, these data suggest that calmodulin has been concentrated at the plasma membrane of unmyelinated axons, most probably by B-50/GAP-43. If the concentrating effect is due to B-50/GAP-43, then there is a possibility that these proteins may be present as a molecular complex in situ. The physiological significance could be that this association regulates the local availability of both B-50/GAP-43 and calmodulin for other interactions.
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the increase in b 50 gap 43 in regenerating rat sciatic nerve occurs predominantly in unmyelinated axon shafts a quantitative ultrastructural study
The Journal of Comparative Neurology, 1995Co-Authors: Paul Verkade, A J Verkleij, A B Oestreicher, W H GispenAbstract:The growth-associated protein B-50/GAP-43 is thought to play a crucial role in axonal growth. We investigated, by quantitative immunoelectron microscopy, whether there are differences in the subcellular distribution of B-50 in unmyelinated and myelinated axons of intact and regenerating sciatic nerves. Adult rats received an unilateral sciatic nerve crush and were euthanized 8 days later. Nerve pieces proximal from the crush site were embedded, and B-50 was visualized by specific B-50 antibodies and immunogold detection in ultrathin sections. The density of B-50 at the plasma membrane of unmyelinated axon shafts was significantly increased in the ipsilateral regenerating nerve in comparison to that of the contralateral intact nerve. In contrast, there was no significant difference in the B-50 density at the Axolemma of myelinated regenerating and intact axon shafts. In the contralateral intact nerve, more B-50 was associated with the Axolemma of unmyelinated axons than with the plasma membrane of myelinated axons. The density of axoplasmic B-50 was similar in intact unmyelinated and myelinated axon shafts, but was higher in regenerating nerve than in intact nerve. This suggests that enhanced axonal transport of B-50 occurs during axon outgrowth. Our study demonstrates a differential subcellular distribution of B-50 in unmyelinated and myelinated axon shafts in both the intact and regenerating sciatic nerve, indicating a differential inducible capacity for remodeling of the axon shafts.