Extracellular Space Diffusion in Central Nervous System: Anisotropic Diffusion Measured by Elliptical Surface Photobleaching
Diffusion in the extracellular space (ECS) is crucial for normal central nervous system physiology. The determinants of ECS diffusion include viscous interactions with extracellular matrix/plasma membranes (“viscosity”) and ECS geometry (“tortuosity”). To resolve viscosity versus tortuosity effects,...
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description | Diffusion in the extracellular space (ECS) is crucial for normal central nervous system physiology. The determinants of ECS diffusion include viscous interactions with extracellular matrix/plasma membranes (“viscosity”) and ECS geometry (“tortuosity”). To resolve viscosity versus tortuosity effects, we measured direction-dependent (anisotropic) diffusion in ECS in mouse spinal cord by photobleaching using an elliptical spot produced by a cylindrical lens in the excitation path. Anisotropic diffusion slowed fluorescence recovery when the long axis of the ellipse was parallel versus perpendicular to the direction of faster diffusion. A mathematical model was constructed to deduce diffusion coefficients (Dx, Dy) from fluorescence recovery measured for parallel and perpendicular orientations of the long axis of the ellipse. Elliptical spot photobleaching was validated by photobleaching aqueous-phase fluorophores on a diffraction grating, where diffusion is one-dimensional. Measurement of the diffusion of 70kDa FITC-dextran in spinal cord in living mice indicated that viscosity slows diffusion by ∼1.8-fold compared with its diffusion in solution. ECS geometry hinders diffusion across (but not along) axonal fibers in spinal cord further by approximately fivefold. In cerebral cortex, however, ∼50% of the hindrance to ECS diffusion comes from viscosity and ∼50% from tortuosity. We suggest that the extracellular matrix might have evolved to facilitate rather than hinder diffusion even for large molecules. |
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The determinants of ECS diffusion include viscous interactions with extracellular matrix/plasma membranes (“viscosity”) and ECS geometry (“tortuosity”). To resolve viscosity versus tortuosity effects, we measured direction-dependent (anisotropic) diffusion in ECS in mouse spinal cord by photobleaching using an elliptical spot produced by a cylindrical lens in the excitation path. Anisotropic diffusion slowed fluorescence recovery when the long axis of the ellipse was parallel versus perpendicular to the direction of faster diffusion. A mathematical model was constructed to deduce diffusion coefficients (Dx, Dy) from fluorescence recovery measured for parallel and perpendicular orientations of the long axis of the ellipse. Elliptical spot photobleaching was validated by photobleaching aqueous-phase fluorophores on a diffraction grating, where diffusion is one-dimensional. Measurement of the diffusion of 70kDa FITC-dextran in spinal cord in living mice indicated that viscosity slows diffusion by ∼1.8-fold compared with its diffusion in solution. ECS geometry hinders diffusion across (but not along) axonal fibers in spinal cord further by approximately fivefold. In cerebral cortex, however, ∼50% of the hindrance to ECS diffusion comes from viscosity and ∼50% from tortuosity. We suggest that the extracellular matrix might have evolved to facilitate rather than hinder diffusion even for large molecules.</description><identifier>ISSN: 0006-3495</identifier><identifier>EISSN: 1542-0086</identifier><identifier>DOI: 10.1529/biophysj.105.068114</identifier><identifier>PMID: 16143636</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Animals ; Anisotropy ; Brain - metabolism ; Central Nervous System - cytology ; Cerebral Cortex - metabolism ; Diffusion ; Extracellular Matrix - metabolism ; Extracellular Space - metabolism ; Fluoresceins - chemistry ; Fluorescence ; Fluorescent Dyes - pharmacology ; Light ; Male ; Mice ; Mice, Inbred C57BL ; Models, Statistical ; Models, Theoretical ; Monte Carlo Method ; Nervous system ; Other ; Photobleaching ; Software ; Spectrometry, Fluorescence ; Spinal Cord - cytology ; Time Factors</subject><ispartof>Biophysical journal, 2005-11, Vol.89 (5), p.3660-3668</ispartof><rights>2005 The Biophysical Society</rights><rights>Copyright Biophysical Society Nov 2005</rights><rights>Copyright © 2005, Biophysical Society 2005</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c515t-f285efb3e0c1621fd32e2dec8005ab197beaabb78fc3ca61f8538617b67ba8733</citedby><cites>FETCH-LOGICAL-c515t-f285efb3e0c1621fd32e2dec8005ab197beaabb78fc3ca61f8538617b67ba8733</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC1366858/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://dx.doi.org/10.1529/biophysj.105.068114$$EHTML$$P50$$Gelsevier$$Hfree_for_read</linktohtml><link.rule.ids>230,314,725,778,782,883,3539,27911,27912,45982,53778,53780</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/16143636$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Papadopoulos, Marios C.</creatorcontrib><creatorcontrib>Kim, Jung Kyung</creatorcontrib><creatorcontrib>Verkman, A.S.</creatorcontrib><title>Extracellular Space Diffusion in Central Nervous System: Anisotropic Diffusion Measured by Elliptical Surface Photobleaching</title><title>Biophysical journal</title><addtitle>Biophys J</addtitle><description>Diffusion in the extracellular space (ECS) is crucial for normal central nervous system physiology. The determinants of ECS diffusion include viscous interactions with extracellular matrix/plasma membranes (“viscosity”) and ECS geometry (“tortuosity”). To resolve viscosity versus tortuosity effects, we measured direction-dependent (anisotropic) diffusion in ECS in mouse spinal cord by photobleaching using an elliptical spot produced by a cylindrical lens in the excitation path. Anisotropic diffusion slowed fluorescence recovery when the long axis of the ellipse was parallel versus perpendicular to the direction of faster diffusion. A mathematical model was constructed to deduce diffusion coefficients (Dx, Dy) from fluorescence recovery measured for parallel and perpendicular orientations of the long axis of the ellipse. Elliptical spot photobleaching was validated by photobleaching aqueous-phase fluorophores on a diffraction grating, where diffusion is one-dimensional. Measurement of the diffusion of 70kDa FITC-dextran in spinal cord in living mice indicated that viscosity slows diffusion by ∼1.8-fold compared with its diffusion in solution. ECS geometry hinders diffusion across (but not along) axonal fibers in spinal cord further by approximately fivefold. In cerebral cortex, however, ∼50% of the hindrance to ECS diffusion comes from viscosity and ∼50% from tortuosity. We suggest that the extracellular matrix might have evolved to facilitate rather than hinder diffusion even for large molecules.</description><subject>Animals</subject><subject>Anisotropy</subject><subject>Brain - metabolism</subject><subject>Central Nervous System - cytology</subject><subject>Cerebral Cortex - metabolism</subject><subject>Diffusion</subject><subject>Extracellular Matrix - metabolism</subject><subject>Extracellular Space - metabolism</subject><subject>Fluoresceins - chemistry</subject><subject>Fluorescence</subject><subject>Fluorescent Dyes - pharmacology</subject><subject>Light</subject><subject>Male</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Models, Statistical</subject><subject>Models, Theoretical</subject><subject>Monte Carlo Method</subject><subject>Nervous system</subject><subject>Other</subject><subject>Photobleaching</subject><subject>Software</subject><subject>Spectrometry, Fluorescence</subject><subject>Spinal Cord - cytology</subject><subject>Time Factors</subject><issn>0006-3495</issn><issn>1542-0086</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2005</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>8G5</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>GUQSH</sourceid><sourceid>M2O</sourceid><recordid>eNqFkluP0zAQhS0EYrsLvwAJRTzwluKJYydFAmlVykVaLlLh2bKd8dZVGmftpKLS_nhcpcDCAzzZsr9zxnM8hDwBOgdeLF5o5_vNIW7nQPmcihqgvEdmwMsip7QW98mMUipyVi74GTmPcUspFJzCQ3IGAkommJiR29X3ISiDbTu2KmTrPu2zN87aMTrfZa7Lltglos0-Ydj7MWbrQxxw9zK77Fz0Q_C9M3cEH1HFMWCT6UO2alvXD84k8XoM9uj8ZeMHr1tUZuO660fkgVVtxMen9YJ8e7v6unyfX31-92F5eZUbDnzIbVFztJohNSAKsA0rsGjQ1JRypWFRaVRK66q2hhklwNac1QIqLSqt6oqxC_J68u1HvcPGTB3JPridCgfplZN_3nRuI6_9XgITouZ1Mnh-Mgj-ZsQ4yJ2Lx9BUhykTKVIVwcv_g1CVRcVFlcBnf4FbP4YupSAL4BVNf7pIEJsgE3yMAe2vJwOVxxmQP2cgHXA5zUBSPb3b7W_N6dMT8GoCMGW-dxhkNA47g40LaAbZePfPAj8A13PIJg</recordid><startdate>20051101</startdate><enddate>20051101</enddate><creator>Papadopoulos, Marios C.</creator><creator>Kim, Jung Kyung</creator><creator>Verkman, A.S.</creator><general>Elsevier Inc</general><general>Biophysical Society</general><scope>6I.</scope><scope>AAFTH</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7QO</scope><scope>7QP</scope><scope>7TK</scope><scope>7TM</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88A</scope><scope>88E</scope><scope>88I</scope><scope>8AF</scope><scope>8AO</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>8G5</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>GUQSH</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M2O</scope><scope>M2P</scope><scope>M7P</scope><scope>MBDVC</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>Q9U</scope><scope>S0X</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20051101</creationdate><title>Extracellular Space Diffusion in Central Nervous System: Anisotropic Diffusion Measured by Elliptical Surface Photobleaching</title><author>Papadopoulos, Marios C. ; Kim, Jung Kyung ; Verkman, A.S.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c515t-f285efb3e0c1621fd32e2dec8005ab197beaabb78fc3ca61f8538617b67ba8733</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2005</creationdate><topic>Animals</topic><topic>Anisotropy</topic><topic>Brain - metabolism</topic><topic>Central Nervous System - cytology</topic><topic>Cerebral Cortex - metabolism</topic><topic>Diffusion</topic><topic>Extracellular Matrix - metabolism</topic><topic>Extracellular Space - metabolism</topic><topic>Fluoresceins - chemistry</topic><topic>Fluorescence</topic><topic>Fluorescent Dyes - pharmacology</topic><topic>Light</topic><topic>Male</topic><topic>Mice</topic><topic>Mice, Inbred C57BL</topic><topic>Models, Statistical</topic><topic>Models, Theoretical</topic><topic>Monte Carlo Method</topic><topic>Nervous system</topic><topic>Other</topic><topic>Photobleaching</topic><topic>Software</topic><topic>Spectrometry, Fluorescence</topic><topic>Spinal Cord - cytology</topic><topic>Time Factors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Papadopoulos, Marios C.</creatorcontrib><creatorcontrib>Kim, Jung Kyung</creatorcontrib><creatorcontrib>Verkman, A.S.</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Biotechnology Research Abstracts</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Agricultural Science Collection</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Biology Database (Alumni Edition)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Science Database (Alumni Edition)</collection><collection>STEM Database</collection><collection>ProQuest Pharma Collection</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Technology Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Research Library (Alumni Edition)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest One Sustainability</collection><collection>ProQuest Central UK/Ireland</collection><collection>Advanced Technologies & Aerospace Collection</collection><collection>Agricultural & Environmental Science Collection</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Technology Collection (ProQuest)</collection><collection>Natural Science Collection (ProQuest)</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>Research Library Prep</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Agricultural Science Database</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Research Library</collection><collection>Science Database (ProQuest)</collection><collection>Biological Science Database</collection><collection>Research Library (Corporate)</collection><collection>Advanced Technologies & Aerospace Database</collection><collection>ProQuest Advanced Technologies & Aerospace Collection</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>ProQuest Central Basic</collection><collection>SIRS Editorial</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Biophysical journal</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Papadopoulos, Marios C.</au><au>Kim, Jung Kyung</au><au>Verkman, A.S.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Extracellular Space Diffusion in Central Nervous System: Anisotropic Diffusion Measured by Elliptical Surface Photobleaching</atitle><jtitle>Biophysical journal</jtitle><addtitle>Biophys J</addtitle><date>2005-11-01</date><risdate>2005</risdate><volume>89</volume><issue>5</issue><spage>3660</spage><epage>3668</epage><pages>3660-3668</pages><issn>0006-3495</issn><eissn>1542-0086</eissn><abstract>Diffusion in the extracellular space (ECS) is crucial for normal central nervous system physiology. The determinants of ECS diffusion include viscous interactions with extracellular matrix/plasma membranes (“viscosity”) and ECS geometry (“tortuosity”). To resolve viscosity versus tortuosity effects, we measured direction-dependent (anisotropic) diffusion in ECS in mouse spinal cord by photobleaching using an elliptical spot produced by a cylindrical lens in the excitation path. Anisotropic diffusion slowed fluorescence recovery when the long axis of the ellipse was parallel versus perpendicular to the direction of faster diffusion. A mathematical model was constructed to deduce diffusion coefficients (Dx, Dy) from fluorescence recovery measured for parallel and perpendicular orientations of the long axis of the ellipse. Elliptical spot photobleaching was validated by photobleaching aqueous-phase fluorophores on a diffraction grating, where diffusion is one-dimensional. Measurement of the diffusion of 70kDa FITC-dextran in spinal cord in living mice indicated that viscosity slows diffusion by ∼1.8-fold compared with its diffusion in solution. ECS geometry hinders diffusion across (but not along) axonal fibers in spinal cord further by approximately fivefold. In cerebral cortex, however, ∼50% of the hindrance to ECS diffusion comes from viscosity and ∼50% from tortuosity. We suggest that the extracellular matrix might have evolved to facilitate rather than hinder diffusion even for large molecules.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>16143636</pmid><doi>10.1529/biophysj.105.068114</doi><tpages>9</tpages><oa>free_for_read</oa></addata></record> |
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subjects | Animals Anisotropy Brain - metabolism Central Nervous System - cytology Cerebral Cortex - metabolism Diffusion Extracellular Matrix - metabolism Extracellular Space - metabolism Fluoresceins - chemistry Fluorescence Fluorescent Dyes - pharmacology Light Male Mice Mice, Inbred C57BL Models, Statistical Models, Theoretical Monte Carlo Method Nervous system Other Photobleaching Software Spectrometry, Fluorescence Spinal Cord - cytology Time Factors |
title | Extracellular Space Diffusion in Central Nervous System: Anisotropic Diffusion Measured by Elliptical Surface Photobleaching |
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