Glutamate Excitotoxicity Inflicts Paranodal Myelin Splitting and Retraction

Fu, Yan; Sun, Wenjing; Shi, Yunzhou; Shi, Riyi; Cheng, Ji‐Xin

doi:10.1371/journal.pone.0006705

Cited by 88 publications

(74 citation statements)

References 52 publications

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“…15 Additionally, CARS has been utilized for intravital imaging of axonal myelin in the sciatic nerve. 16,17 However, longitudinal in vivo CARS imaging, especially for the spinal cord, has been hindered by several challenges including 1. invasive surgical procedures to expose the cord for imaging with a traditional microscope objective complicate animal survivability, 2. motion of the spinal cord tissue arising from the animal's respiration and heart-beat results in image distortion, 3. blood deposition on the spinal cord reduces optical penetration, and 4. scar-tissue formation complicates subsequent exposure of spinal tissues.…”

Section: Introductionmentioning

confidence: 99%

Longitudinal in vivo coherent anti-Stokes Raman scattering imaging of demyelination and remyelination in injured spinal cord

et al. 2011

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Abstract. In vivo imaging of white matter is important for the mechanistic understanding of demyelination and evaluation of remyelination therapies. Although white matter can be visualized by a strong coherent anti-Stokes Raman scattering (CARS) signal from axonal myelin, in vivo repetitive CARS imaging of the spinal cord remains a challenge due to complexities induced by the laminectomy surgery. We present a careful experimental design that enabled longitudinal CARS imaging of de-and remyelination at single axon level in live rats. In vivo CARS imaging of secretory phospholipase A 2 induced myelin vesiculation, macrophage uptake of myelin debris, and spontaneous remyelination by Schwann cells are sequentially monitored over a 3 week period. Longitudinal visualization of de-and remyelination at a single axon level provides a novel platform for rational design of therapies aimed at promoting myelin plasticity and repair. C 2011 Society of Photo-Optical Instrumentation Engineers (SPIE).

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Section: Introductionmentioning

confidence: 99%

Longitudinal in vivo coherent anti-Stokes Raman scattering imaging of demyelination and remyelination in injured spinal cord

et al. 2011

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“…However, such acute myelin damage is likely to be exacerbated by the secondary biochemical cascades that are also known to damage myelin [31,32] . Therefore, the severe myelin damage observed in chronic nerve injury almost certainly results from both acute, mechanical trauma and the secondary biochemical deterioration.…”

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Potassium channel blockers as an effective treatment to restore impulse conduction in injured axons

Shi

Sun

2011

Neurosci. Bull.

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Most axons in the vertebral central nervous system are myelinated by oligodendrocytes. Myelin protects and insulates neuronal processes, enabling the fast, saltatory conduction unique to myelinated axons. Myelin disruption resulting from trauma and biochemical reaction is a common pathological event in spinal cord injury and chronic neurodegenerative diseases. Myelin damage-induced axonal conduction block is considered to be a significant contributor to the devastating neurological deficits resulting from trauma and illness. Potassium channels are believed to play an important role in axonal conduction failure in spinal cord injury and multiple sclerosis. Myelin damage has been shown to unmask potassium channels, creating aberrant potassium currents that inhibit conduction. Potassium channel blockade reduces this ionic leakage and improves conduction. The present review was mainly focused on the development of this technique of restoring axonal conduction and neurological function of demyelinated axons. The drug 4-aminopyridine has recently shown clinical success in treating multiple sclerosis symptoms. Further translational research has also identified several novel potassium channel blockers that may prove effective in restoring axonal conduction.

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“…Second, CARS imaging does not require labeling for visualization; thus, it allows long-term visualization of the myelin sheaths ( 41,115 ). Third, CARS-based multimodal microscopy allows simultaneous visualization of myelin sheaths and cellular processes during demyelination (111)(112)(113). This capability is invaluable to the studies of molecular mechanisms underlying myelin diseases.…”

Section: Study Of Lipids In Cancer Developmentmentioning

confidence: 99%

Shedding new light on lipid biology with coherent anti-Stokes Raman scattering microscopy

Yue

Cheng

2010

Journal of Lipid Research

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Despite the ubiquitous roles of lipids in biology, the detection of lipids has relied on invasive techniques and population measurements. The molecular profi les of the lipid-rich structures are evaluated by measurements of total lipid extracts with liquid or gas chromatography coupled to mass spectrometry ( 8 ). This approach is inexact because it measures lipid molecules from areas other than the structures of interest. Furthermore, spatial information, which is critical to understanding the function of lipids ( 9 ), is inaccessible with the bulk measurement techniques. To visualize the lipid-rich structures, fl uorescently tagged lipid molecules, which intercalate with the lipidrich structures, are used ( 10, 11 ). Nevertheless, the use of the fl uorescent lipid molecules to label lipid-rich structures is problematic for several reasons. First, to facilitate the transport of the fl uorescent lipid molecules into cells, cell fi xation procedures are often performed ( 12 ). This procedure prevents monitoring the dynamic responses of lipid-rich structures to stimuli or the disease processes. Second, labeling effi ciency is highly dependent on the type of fl uorescent lipid molecules ( 12 ), thus posing a signifi cant problem to the quantitation of lipid-rich structures. Third, the intercalation of fl uorescent lipid molecules can lead to changes in the properties of lipidrich structures. For instance, incorporation of fl uorescent lipid molecules into the cell membrane can induce membrane phase separation and membrane microdomain formation, which can perturb critical cellular processes including signal transduction and endocytosis ( 13 ).As an alternative to fl uorescence, signals from molecular vibration provide an attractive means for label-free chemical imaging. In particular, Raman scattering has been widely used for spectroscopic study of biomolecules ( 14 ). The Raman-scattered photons exhibit frequency Abstract Despite the ubiquitous roles of lipids in biology, the detection of lipids has relied on invasive techniques, population measurements, or nonspecifi c labeling. Such diffi culties can be circumvented by a label-free imaging technique known as coherent anti-Stokes Raman (CARS) microscopy, which is capable of chemically selective, highly sensitive, and high-speed imaging of lipid-rich structures with submicron three-dimensional spatial resolution. We review the broad applications of CARS microscopy to studies of lipid biology in cell cultures, tissue biopsies, and model organisms. Recent technical advances, limitations of the technique, and perspectives are discussed. Lipids play a critical role in human health and diseases. Phospholipids, glycolipids, and sterol lipids are the major components of the cell membrane ( 1 ). Sphingolipids constitute up to 80% of the myelin sheaths, which are the membranous structures that wrap around the axons for insulation and for proper propagation of electrical impulses ( 2 ). Glycerolipids or triglycerides serve as the cytoplasmic energy depots ( 3 ). Bioactive lip...

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Glutamate Excitotoxicity Inflicts Paranodal Myelin Splitting and Retraction

Cited by 88 publications

References 52 publications

Longitudinal in vivo coherent anti-Stokes Raman scattering imaging of demyelination and remyelination in injured spinal cord

Longitudinal in vivo coherent anti-Stokes Raman scattering imaging of demyelination and remyelination in injured spinal cord

Potassium channel blockers as an effective treatment to restore impulse conduction in injured axons

Shedding new light on lipid biology with coherent anti-Stokes Raman scattering microscopy

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