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Damage to myelin and oligodendrocytes: a role in chronic outcomes following traumatic brain injury?

Maxwell WL - Brain Sci (2013)

Bottom Line: However, the biomechanism(s) of continued loss of axons is obscure.Waves of Ca2+ depolarization or spreading depression extend from the initial locus injury for perhaps hundreds of microns after TBI.As astrocytes and oligodendrocytes are connected via gap junctions, it is hypothesized that spreading depression results in depolarization of central glia, disrupt axonal ionic homeostasis, injure axonal mitochondria and allow the onset of axonal degeneration throughout an increasing volume of brain tissue; and contribute toward post-traumatic continued loss of white matter.

View Article: PubMed Central - PubMed

Affiliation: Department of Human Anatomy, College of Medicine, Veterinary Medicine and Biological Sciences, University of Glasgow, Glasgow G12 8QQ, UK. William.Maxwell@Glasgow.ac.uk.

ABSTRACT
There is increasing evidence in the experimental and clinical traumatic brain injury (TBI) literature that loss of central myelinated nerve fibers continues over the chronic post-traumatic phase after injury. However, the biomechanism(s) of continued loss of axons is obscure. Stretch-injury to optic nerve fibers in adult guinea-pigs was used to test the hypothesis that damage to the myelin sheath and oligodendrocytes of the optic nerve fibers may contribute to, or facilitate, the continuance of axonal loss. Myelin dislocations occur within internodal myelin of larger axons within 1-2 h of TBI. The myelin dislocations contain elevated levels of free calcium. The volume of myelin dislocations increase with greater survival and are associated with disruption of the axonal cytoskeleton leading to secondary axotomy. Waves of Ca2+ depolarization or spreading depression extend from the initial locus injury for perhaps hundreds of microns after TBI. As astrocytes and oligodendrocytes are connected via gap junctions, it is hypothesized that spreading depression results in depolarization of central glia, disrupt axonal ionic homeostasis, injure axonal mitochondria and allow the onset of axonal degeneration throughout an increasing volume of brain tissue; and contribute toward post-traumatic continued loss of white matter.

No MeSH data available.


Related in: MedlinePlus

Thin sections of stretch-injured optic nerve at 12 h survival. Tissue was processed using the pyroantimonate technique. (a) At lower magification of longitudinal/oblique sections of nerve fibers nodal structure appears normal (center) except for some disruption of the paranodal myelin. In the larger caliber nerve fibers, however, mds now extend either inside (myelin intrusions, mi) or outside (external protrusions, ep) the thickness of the myelin sheath and contain pyroantimonate precipitate. Myelin discontinuities/intrusions/extrusions are more numerous in larger than in the smaller fibers (within the oval profile above the node of Ranvier). The greater circumferential disruption formed by md, mp and me is obvious in transverse sections of nerve fibers (b) and are more numerous and extensive within the myelin sheath of larger fibers. The axons have an irregular cross-section and a number of periaxonal spaces (pa) occur between the axon and the myelin sheath. Mitochondria within the axoplasm either contain aggregates of pyroantimonate precipitate (arrow) or have a central lacuna (double arrow). The axoplasm of the nerve fibers contains closely spaced microtubules and neurofilaments which form spiral arrays. Magnification (a) 7500×; (b) 23,450×.
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brainsci-03-01374-f008: Thin sections of stretch-injured optic nerve at 12 h survival. Tissue was processed using the pyroantimonate technique. (a) At lower magification of longitudinal/oblique sections of nerve fibers nodal structure appears normal (center) except for some disruption of the paranodal myelin. In the larger caliber nerve fibers, however, mds now extend either inside (myelin intrusions, mi) or outside (external protrusions, ep) the thickness of the myelin sheath and contain pyroantimonate precipitate. Myelin discontinuities/intrusions/extrusions are more numerous in larger than in the smaller fibers (within the oval profile above the node of Ranvier). The greater circumferential disruption formed by md, mp and me is obvious in transverse sections of nerve fibers (b) and are more numerous and extensive within the myelin sheath of larger fibers. The axons have an irregular cross-section and a number of periaxonal spaces (pa) occur between the axon and the myelin sheath. Mitochondria within the axoplasm either contain aggregates of pyroantimonate precipitate (arrow) or have a central lacuna (double arrow). The axoplasm of the nerve fibers contains closely spaced microtubules and neurofilaments which form spiral arrays. Magnification (a) 7500×; (b) 23,450×.

Mentions: With increasing survival after injury there is an apparent increase in volume of myelin discontinuities (md) (Figure 8a), together with a raised intra-axonal content of pyroantimonate precipitate. In a low magnification field at 12 h survival myelin discontinuities occur more frequently in larger nerve fibres and mds now protrude into the perimeter of the axon (Figure 8a, arrows). However, and in particular in the context of this special issue on myelin and myelin repair, very little attention has been paid to analysis of responses within the myelin sheath of injured central white matter, for example in models of stroke [21] and in trauma [22,23,24].


Damage to myelin and oligodendrocytes: a role in chronic outcomes following traumatic brain injury?

Maxwell WL - Brain Sci (2013)

Thin sections of stretch-injured optic nerve at 12 h survival. Tissue was processed using the pyroantimonate technique. (a) At lower magification of longitudinal/oblique sections of nerve fibers nodal structure appears normal (center) except for some disruption of the paranodal myelin. In the larger caliber nerve fibers, however, mds now extend either inside (myelin intrusions, mi) or outside (external protrusions, ep) the thickness of the myelin sheath and contain pyroantimonate precipitate. Myelin discontinuities/intrusions/extrusions are more numerous in larger than in the smaller fibers (within the oval profile above the node of Ranvier). The greater circumferential disruption formed by md, mp and me is obvious in transverse sections of nerve fibers (b) and are more numerous and extensive within the myelin sheath of larger fibers. The axons have an irregular cross-section and a number of periaxonal spaces (pa) occur between the axon and the myelin sheath. Mitochondria within the axoplasm either contain aggregates of pyroantimonate precipitate (arrow) or have a central lacuna (double arrow). The axoplasm of the nerve fibers contains closely spaced microtubules and neurofilaments which form spiral arrays. Magnification (a) 7500×; (b) 23,450×.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4061868&req=5

brainsci-03-01374-f008: Thin sections of stretch-injured optic nerve at 12 h survival. Tissue was processed using the pyroantimonate technique. (a) At lower magification of longitudinal/oblique sections of nerve fibers nodal structure appears normal (center) except for some disruption of the paranodal myelin. In the larger caliber nerve fibers, however, mds now extend either inside (myelin intrusions, mi) or outside (external protrusions, ep) the thickness of the myelin sheath and contain pyroantimonate precipitate. Myelin discontinuities/intrusions/extrusions are more numerous in larger than in the smaller fibers (within the oval profile above the node of Ranvier). The greater circumferential disruption formed by md, mp and me is obvious in transverse sections of nerve fibers (b) and are more numerous and extensive within the myelin sheath of larger fibers. The axons have an irregular cross-section and a number of periaxonal spaces (pa) occur between the axon and the myelin sheath. Mitochondria within the axoplasm either contain aggregates of pyroantimonate precipitate (arrow) or have a central lacuna (double arrow). The axoplasm of the nerve fibers contains closely spaced microtubules and neurofilaments which form spiral arrays. Magnification (a) 7500×; (b) 23,450×.
Mentions: With increasing survival after injury there is an apparent increase in volume of myelin discontinuities (md) (Figure 8a), together with a raised intra-axonal content of pyroantimonate precipitate. In a low magnification field at 12 h survival myelin discontinuities occur more frequently in larger nerve fibres and mds now protrude into the perimeter of the axon (Figure 8a, arrows). However, and in particular in the context of this special issue on myelin and myelin repair, very little attention has been paid to analysis of responses within the myelin sheath of injured central white matter, for example in models of stroke [21] and in trauma [22,23,24].

Bottom Line: However, the biomechanism(s) of continued loss of axons is obscure.Waves of Ca2+ depolarization or spreading depression extend from the initial locus injury for perhaps hundreds of microns after TBI.As astrocytes and oligodendrocytes are connected via gap junctions, it is hypothesized that spreading depression results in depolarization of central glia, disrupt axonal ionic homeostasis, injure axonal mitochondria and allow the onset of axonal degeneration throughout an increasing volume of brain tissue; and contribute toward post-traumatic continued loss of white matter.

View Article: PubMed Central - PubMed

Affiliation: Department of Human Anatomy, College of Medicine, Veterinary Medicine and Biological Sciences, University of Glasgow, Glasgow G12 8QQ, UK. William.Maxwell@Glasgow.ac.uk.

ABSTRACT
There is increasing evidence in the experimental and clinical traumatic brain injury (TBI) literature that loss of central myelinated nerve fibers continues over the chronic post-traumatic phase after injury. However, the biomechanism(s) of continued loss of axons is obscure. Stretch-injury to optic nerve fibers in adult guinea-pigs was used to test the hypothesis that damage to the myelin sheath and oligodendrocytes of the optic nerve fibers may contribute to, or facilitate, the continuance of axonal loss. Myelin dislocations occur within internodal myelin of larger axons within 1-2 h of TBI. The myelin dislocations contain elevated levels of free calcium. The volume of myelin dislocations increase with greater survival and are associated with disruption of the axonal cytoskeleton leading to secondary axotomy. Waves of Ca2+ depolarization or spreading depression extend from the initial locus injury for perhaps hundreds of microns after TBI. As astrocytes and oligodendrocytes are connected via gap junctions, it is hypothesized that spreading depression results in depolarization of central glia, disrupt axonal ionic homeostasis, injure axonal mitochondria and allow the onset of axonal degeneration throughout an increasing volume of brain tissue; and contribute toward post-traumatic continued loss of white matter.

No MeSH data available.


Related in: MedlinePlus