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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

Examples of the ultrastructure of gap junctions between (a) astrocytes and (b) oligodendrocytes within the mammalian CNS. A gap junction appears as an electron dense apposition of neighboring cell membranes between two cells. Apposed surfaces of adjacent cell membranes are interconnected by connexon proteins forming molecular channels allowing passage of molecules/ions of less than 1000 Da between cells. Magnification 43,600×.
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brainsci-03-01374-f011: Examples of the ultrastructure of gap junctions between (a) astrocytes and (b) oligodendrocytes within the mammalian CNS. A gap junction appears as an electron dense apposition of neighboring cell membranes between two cells. Apposed surfaces of adjacent cell membranes are interconnected by connexon proteins forming molecular channels allowing passage of molecules/ions of less than 1000 Da between cells. Magnification 43,600×.

Mentions: Recent evidence has strongly suggested that intercellular relationships, and probably functions, within central white matter are more complex than appreciated even less than a decade ago [1,18,19]. Rather than the earlier concept that mature oligodendrocytes assume a quiescent state upon completion of myelination, there is now a consensus that considerable intercellular exchange occurs between the neuronal axon, oligodendrocytes and perinodal astrocytes within central white matter [18]. Astrocytes and oligodendrocytes within the CNS are linked by multiple gap junctions during myelination [36] and in mature white matter [19] (Figure 11). It has recently been reported that various types of mechanical load, like strain, pressure, shear stress, or cyclic stretch can influence oligodendrocyte cell biology and intercellular communication via gap junctions between neighboring mature oligodendrocytes as well as between mature oligodendrocytes and astrocytes [37] both of which intimately interact with CNS neurons. Gap junctions form narrow channels connecting the cytoplasm of adjacent or linked cells (Figure 11) allowing passage of molecules or ions of less than 1000 Da and electrical current [19,37] and such channels may be visualized at the light microscope level by use of biocytin which readily passes through gap junctions and into the oligodendrocyte cytoplasm [19] or at the ultrastructural level (Figure 11).


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

Maxwell WL - Brain Sci (2013)

Examples of the ultrastructure of gap junctions between (a) astrocytes and (b) oligodendrocytes within the mammalian CNS. A gap junction appears as an electron dense apposition of neighboring cell membranes between two cells. Apposed surfaces of adjacent cell membranes are interconnected by connexon proteins forming molecular channels allowing passage of molecules/ions of less than 1000 Da between cells. Magnification 43,600×.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

brainsci-03-01374-f011: Examples of the ultrastructure of gap junctions between (a) astrocytes and (b) oligodendrocytes within the mammalian CNS. A gap junction appears as an electron dense apposition of neighboring cell membranes between two cells. Apposed surfaces of adjacent cell membranes are interconnected by connexon proteins forming molecular channels allowing passage of molecules/ions of less than 1000 Da between cells. Magnification 43,600×.
Mentions: Recent evidence has strongly suggested that intercellular relationships, and probably functions, within central white matter are more complex than appreciated even less than a decade ago [1,18,19]. Rather than the earlier concept that mature oligodendrocytes assume a quiescent state upon completion of myelination, there is now a consensus that considerable intercellular exchange occurs between the neuronal axon, oligodendrocytes and perinodal astrocytes within central white matter [18]. Astrocytes and oligodendrocytes within the CNS are linked by multiple gap junctions during myelination [36] and in mature white matter [19] (Figure 11). It has recently been reported that various types of mechanical load, like strain, pressure, shear stress, or cyclic stretch can influence oligodendrocyte cell biology and intercellular communication via gap junctions between neighboring mature oligodendrocytes as well as between mature oligodendrocytes and astrocytes [37] both of which intimately interact with CNS neurons. Gap junctions form narrow channels connecting the cytoplasm of adjacent or linked cells (Figure 11) allowing passage of molecules or ions of less than 1000 Da and electrical current [19,37] and such channels may be visualized at the light microscope level by use of biocytin which readily passes through gap junctions and into the oligodendrocyte cytoplasm [19] or at the ultrastructural level (Figure 11).

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