Reduced extracellular space in the brain of tenascin‐R‐ and HNK‐1‐sulphotransferase deficient mice

Syková, Eva; Voříšek, Ivan; Mazel, Tomáš; Antonova, Tatiana; Schachner, Melitta

doi:10.1111/j.1460-9568.2005.04375.x

Cited by 67 publications

(61 citation statements)

References 49 publications

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“…It may be possible that degradation of hyaluronan led to a collapse of the space between some cells. Sykova and colleagues reported that knockout mice lacking tenascin-C, a key structural element of the brain ECM, exhibit a decrease in both the porosity and tortuosity [47]. It is possible that hyaluronan degradation reduced physical barriers to transport, but a simultaneous decrease in the porosity may have resulted in "lakes" at the interstices of some cells.…”

Section: Discussionmentioning

confidence: 99%

Dilation and degradation of the brain extracellular matrix enhances penetration of infused polymer nanoparticles

et al. 2007

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This study investigates methods of manipulating the brain extracellular matrix (ECM) to enhance the penetration of nanoparticle drug carriers in convection-enhanced delivery (CED). A probe was fabricated with two independent microfluidic channels to infuse, either simultaneously or sequentially, nanoparticles and ECM-modifying agents. Infusions were performed in the striatum of the normal rat brain. Monodisperse polystyrene particles with a diameter of 54 nm were used as a model nanoparticle system. Because the size of these particles is comparable to the effective pore size of the ECM, their transport may be significantly hindered compared with the transport of low molecular weight molecules. To enhance the transport of the infused nanoparticles, we attempted to increase the effective pore size of the ECM by two methods: dilating the extracellular space and degrading selected constituents of the ECM. Two methods of dilating the extracellular space were investigated: co-infusion of nanoparticles and a hyperosmolar solution of mannitol, and pre-infusion of an isotonic buffer solution followed by infusion of nanoparticles. These treatments resulted in an increase in the nanoparticle distribution volume of 50% and 123%, respectively. To degrade hyaluronan, a primary structural component of the brain ECM, a pre-infusion of hyaluronidase (20,000 U/mL) was followed after 30 min by infusion of nanoparticles. This treatment resulted in an increase in the nanoparticle distribution of 64%. Our results suggest that both dilation and enzymatic digestion can be incorporated into CED protocols to enhance nanoparticle penetration.

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Section: Discussionmentioning

confidence: 99%

Dilation and degradation of the brain extracellular matrix enhances penetration of infused polymer nanoparticles

et al. 2007

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“…Values of ␣ (0.18 -0.19) and (1.61) found in wildtype mice in the present study can be compared with other in vivo studies on wild-type mouse cortex. For ages 3-6 months, Anděrová et al (2001) found ␣ ϭ 0.23, ϭ 1.67; for ages 6 -8 months, Syková et al (2005a) reported ␣ ϭ 0.20, ϭ 1.47-1.50; for ages 5-9 months, Syková et al (2005b) reported ␣ ϭ 0.17, ϭ 1.57. Variations among mouse strains probably account for the small differences in values.…”

Section: Comparison With Other Wild-type Mouse Studiesmentioning

confidence: 97%

Aquaporin-4-Deficient Mice Have Increased Extracellular Space without Tortuosity Change

Yao¹,

Hrabětová²,

Nicholson³

et al. 2008

J. Neurosci.

136

113

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Aquaporin-4 (AQP4) isϪ/Ϫ mice, and no differences in and k between the two genotypes. This is the first direct comparison of ECS properties in adult mice lacking AQP4 water channels with wild-type animals and demonstrates a significant enlargement of the volume fraction but no difference in hindrance to TMA ϩ diffusion, expressed as tortuosity. These findings provide direct evidence for involvement of AQP4 in modulation of the ECS volume fraction and provide a basis for future modeling of water and ion transport in the CNS.

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“…For MRI measurements the animals were anesthetized with isoflurane (1.5% in a mixture consisting of 40% O 2 and 60% N 2 O) and placed in a heated mouse holder. Diffusion-weighted (DW) MRI measurements were performed as described previously (Syková et al, 2005), using an experimental MR spectrometer BIOSPEC 4.7 T system (Bruker) equipped with a 200 mT/m gradient system (190 s rise time) and a homemade head surface coil. Coronal slices, were acquired using the following parameters: ⌬ ϭ 30 ms, b-factors ϭ 136, 329, 675, 1035, 1481 and 1825 s/mm 2 , echo time ϭ 46 ms, repetition time ϭ 1200 ms, field of view 1.92 ϫ 1.92 cm 2 , matrix size ϭ 256 ϫ 128, four 0.8-mm-thick coronal slices, interslice distance ϭ 1.2 mm.…”

Section: Methodsmentioning

confidence: 99%

“…ECM mol-ecules play a role in tissue cytoarchitecture by maintaining the optimal size of intercellular pores and by creating diffusion barriers (Roitbak and Syková, 1999;Zámecník et al, 2004;Syková et al, 2005). Diffusion barriers formed by myelin sheaths, glial processes and the ECM may channel the diffusion of molecules in a certain direction, so that diffusion is anisotropic, i.e., unequal along different axes (Prokopová et al, 1997;Vorísek and Syková, 1997).…”

Section: Introductionmentioning

confidence: 99%

Bral1: Its Role in Diffusion Barrier Formation and Conduction Velocity in the CNS

et al. 2010

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At the nodes of Ranvier, excitable axon membranes are exposed directly to the extracellular fluid. Cations are accumulated and depleted in the local extracellular nodal region during action potential propagation, but the impact of the extranodal micromilieu on signal propagation still remains unclear. Brain-specific hyaluronan-binding link protein, Bral1, colocalizes and forms complexes with negatively charged extracellular matrix (ECM) proteins, such as versican V2 and brevican, at the nodes of Ranvier in the myelinated white matter. The link protein family, including Bral1, appears to be the linchpin of these hyaluronan-bound ECM complexes. Here we report that the hyaluronan-associated ECM no longer shows a nodal pattern and that CNS nerve conduction is markedly decreased in Bral1-deficient mice even though there were no differences between wild-type and mutant mice in the clustering or transition of ion channels at the nodes or in the tissue morphology around the nodes of Ranvier. However, changes in the extracellular space diffusion parameters, measured by the real-time iontophoretic method and diffusion-weighted magnetic resonance imaging (MRI), suggest a reduction in the diffusion hindrances in the white matter of mutant mice. These findings provide a better understanding of the mechanisms underlying the accumulation of cations due to diffusion barriers around the nodes during saltatory conduction, which further implies the importance of the Bral1-based extramilieu for neuronal conductivity.

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Reduced extracellular space in the brain of tenascin‐R‐ and HNK‐1‐sulphotransferase deficient mice

Cited by 67 publications

References 49 publications

Dilation and degradation of the brain extracellular matrix enhances penetration of infused polymer nanoparticles

Dilation and degradation of the brain extracellular matrix enhances penetration of infused polymer nanoparticles

Aquaporin-4-Deficient Mice Have Increased Extracellular Space without Tortuosity Change

Bral1: Its Role in Diffusion Barrier Formation and Conduction Velocity in the CNS

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