Spatiotemporal dynamics of PDGFRβ expression in pericytes and glial scar formation in penetrating brain injuries in adults
Aims Understanding the spatiotemporal dynamics of reactive cell types following brain injury is important for future therapeutic interventions. We have previously used penetrating cortical injuries following intracranial recordings as a brain repair model to study scar‐forming nestin‐expressing cell...
Gespeichert in:
| Veröffentlicht in: | Neuropathology and applied neurobiology 2019-10, Vol.45 (6), p.609-627 |
|---|---|
| Hauptverfasser: | , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 627 |
|---|---|
| container_issue | 6 |
| container_start_page | 609 |
| container_title | Neuropathology and applied neurobiology |
| container_volume | 45 |
| creator | Reeves, C. Pradim‐Jardim, A. Sisodiya, S. M. Thom, M. Liu, J. Y. W. |
| description | Aims
Understanding the spatiotemporal dynamics of reactive cell types following brain injury is important for future therapeutic interventions. We have previously used penetrating cortical injuries following intracranial recordings as a brain repair model to study scar‐forming nestin‐expressing cells. We now explore the relationship between nestin‐expressing cells, PDGFRβ+ pericytes and Olig2+ glia, including their proliferation and functional maturation.
Methods
In 32 cases, ranging from 3 to 461 days post injury (dpi), immunohistochemistry for PDGFRβ, nestin, GFAP, Olig2, MCM2, Aquaporin 4 (Aq4), Glutamine Synthetase (GS) and Connexin 43 (Cx43) was quantified for cell densities, labelling index (LI) and cellular co‐expression at the injury site compared to control regions.
Results
PDGFRβ labelling highlighted both pericytes and multipolar parenchymal cells. PDGFRβ LI and PDGFRβ+/MCM2+ cells significantly increased in injury Zones at 10–13 dpi with migration of pericytes away from vessels with increased co‐localization of PDGRFβ with nestin compared to control regions (P |
| doi_str_mv | 10.1111/nan.12539 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_6767497</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2292335423</sourcerecordid><originalsourceid>FETCH-LOGICAL-c4439-d36b874ef518a1c10604d2c9b4e81e1a856fe9435dc8081480c35e352e2d845e3</originalsourceid><addsrcrecordid>eNp1kc1u1DAUhS0EosPAghdAltjAIq0d_8TeIFWFFqSqIH7Wlse5GTxK7GAnwIi36oP0mfAwQwVIeGHfa3_36FgHoceUHNOyToINx7QWTN9BC8qkqGqtyV20IIyIiiouj9CDnDeEENFIfR8dMSKZJE2zQD8-jHbycYJhjMn2uN0GO3iXcezwu5cX5-9vrjF8HxPk7GPAPuARknfbCTK2ocXr3pep7GzCXUzDTutABZhSacMar5L1u8vNnHwZK7Vt537KD9G9zvYZHh3OJfp0_urj2evq8u3Fm7PTy8pxznTVMrlSDYdOUGWpo0QS3tZOrzgoCtQqITvQnInWKaIoV8QxAUzUULeKl2qJXux1x3k1QOsgFGe9GZMfbNqaaL35-yX4z2YdvxrZyIbrpgg8Owik-GWGPJnBZwd9bwPEOZuaNpo1VAte0Kf_oJs4p1C-Z-pa14wJXrYler6nXIo5J-huzVBidpGaEqn5FWlhn_zp_pb8nWEBTvbAN9_D9v9K5ur0ai_5E8-mrY4</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2292335423</pqid></control><display><type>article</type><title>Spatiotemporal dynamics of PDGFRβ expression in pericytes and glial scar formation in penetrating brain injuries in adults</title><source>MEDLINE</source><source>Wiley Online Library Journals Frontfile Complete</source><creator>Reeves, C. ; Pradim‐Jardim, A. ; Sisodiya, S. M. ; Thom, M. ; Liu, J. Y. W.</creator><creatorcontrib>Reeves, C. ; Pradim‐Jardim, A. ; Sisodiya, S. M. ; Thom, M. ; Liu, J. Y. W.</creatorcontrib><description><![CDATA[Aims
Understanding the spatiotemporal dynamics of reactive cell types following brain injury is important for future therapeutic interventions. We have previously used penetrating cortical injuries following intracranial recordings as a brain repair model to study scar‐forming nestin‐expressing cells. We now explore the relationship between nestin‐expressing cells, PDGFRβ+ pericytes and Olig2+ glia, including their proliferation and functional maturation.
Methods
In 32 cases, ranging from 3 to 461 days post injury (dpi), immunohistochemistry for PDGFRβ, nestin, GFAP, Olig2, MCM2, Aquaporin 4 (Aq4), Glutamine Synthetase (GS) and Connexin 43 (Cx43) was quantified for cell densities, labelling index (LI) and cellular co‐expression at the injury site compared to control regions.
Results
PDGFRβ labelling highlighted both pericytes and multipolar parenchymal cells. PDGFRβ LI and PDGFRβ+/MCM2+ cells significantly increased in injury Zones at 10–13 dpi with migration of pericytes away from vessels with increased co‐localization of PDGRFβ with nestin compared to control regions (P < 0.005). Olig2+/MCM2+ cell populations peaked at 13 dpi with significantly higher cell densities at injury sites than in control regions (P < 0.01) and decreasing with dpi (P < 0.05). Cx43 LI was reduced in acute injuries but increased with dpi (P < 0.05) showing significant cellular co‐localization with nestin and GFAP (P < 0.005 and P < 0.0001) but not PDGFRβ.
Conclusions
These findings indicate that PDGFRβ+ and Olig2+ cells contribute to the proliferative fraction following penetrating brain injuries, with evidence of pericyte migration. Dynamic changes in Cx43 in glial cell types with dpi suggest functional alterations during temporal stages of brain repair.]]></description><identifier>ISSN: 0305-1846</identifier><identifier>EISSN: 1365-2990</identifier><identifier>DOI: 10.1111/nan.12539</identifier><identifier>PMID: 30636077</identifier><language>eng</language><publisher>England: Wiley Subscription Services, Inc</publisher><subject>Adolescent ; Adult ; Aged, 80 and over ; Aquaporin 4 ; Brain - metabolism ; Brain - pathology ; Brain injury ; Cell proliferation ; Connexin 43 ; Cortex ; Female ; Glial fibrillary acidic protein ; Glial Fibrillary Acidic Protein - metabolism ; glial scar ; Gliosis - metabolism ; Gliosis - pathology ; Glutamate-ammonia ligase ; Glutamine ; Head Injuries, Penetrating - metabolism ; Head Injuries, Penetrating - pathology ; Humans ; Immunohistochemistry ; Labeling ; Localization ; Male ; Middle Aged ; Nestin ; Olig2 protein ; Original ; Pericytes ; Pericytes - metabolism ; Pericytes - pathology ; progenitors ; Receptor, Platelet-Derived Growth Factor beta - metabolism ; Therapeutic applications ; Traumatic brain injury ; Young Adult</subject><ispartof>Neuropathology and applied neurobiology, 2019-10, Vol.45 (6), p.609-627</ispartof><rights>2019 The Authors. published by John Wiley & Sons Ltd on behalf of British Neuropathological Society</rights><rights>2019 The Authors. Neuropathology and Applied Neurobiology published by John Wiley & Sons Ltd on behalf of British Neuropathological Society.</rights><rights>Copyright © 2019 British Neuropathological Society</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4439-d36b874ef518a1c10604d2c9b4e81e1a856fe9435dc8081480c35e352e2d845e3</citedby><cites>FETCH-LOGICAL-c4439-d36b874ef518a1c10604d2c9b4e81e1a856fe9435dc8081480c35e352e2d845e3</cites><orcidid>0000-0001-7712-2629</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1111%2Fnan.12539$$EPDF$$P50$$Gwiley$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1111%2Fnan.12539$$EHTML$$P50$$Gwiley$$Hfree_for_read</linktohtml><link.rule.ids>230,314,776,780,881,1411,27901,27902,45550,45551</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/30636077$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Reeves, C.</creatorcontrib><creatorcontrib>Pradim‐Jardim, A.</creatorcontrib><creatorcontrib>Sisodiya, S. M.</creatorcontrib><creatorcontrib>Thom, M.</creatorcontrib><creatorcontrib>Liu, J. Y. W.</creatorcontrib><title>Spatiotemporal dynamics of PDGFRβ expression in pericytes and glial scar formation in penetrating brain injuries in adults</title><title>Neuropathology and applied neurobiology</title><addtitle>Neuropathol Appl Neurobiol</addtitle><description><![CDATA[Aims
Understanding the spatiotemporal dynamics of reactive cell types following brain injury is important for future therapeutic interventions. We have previously used penetrating cortical injuries following intracranial recordings as a brain repair model to study scar‐forming nestin‐expressing cells. We now explore the relationship between nestin‐expressing cells, PDGFRβ+ pericytes and Olig2+ glia, including their proliferation and functional maturation.
Methods
In 32 cases, ranging from 3 to 461 days post injury (dpi), immunohistochemistry for PDGFRβ, nestin, GFAP, Olig2, MCM2, Aquaporin 4 (Aq4), Glutamine Synthetase (GS) and Connexin 43 (Cx43) was quantified for cell densities, labelling index (LI) and cellular co‐expression at the injury site compared to control regions.
Results
PDGFRβ labelling highlighted both pericytes and multipolar parenchymal cells. PDGFRβ LI and PDGFRβ+/MCM2+ cells significantly increased in injury Zones at 10–13 dpi with migration of pericytes away from vessels with increased co‐localization of PDGRFβ with nestin compared to control regions (P < 0.005). Olig2+/MCM2+ cell populations peaked at 13 dpi with significantly higher cell densities at injury sites than in control regions (P < 0.01) and decreasing with dpi (P < 0.05). Cx43 LI was reduced in acute injuries but increased with dpi (P < 0.05) showing significant cellular co‐localization with nestin and GFAP (P < 0.005 and P < 0.0001) but not PDGFRβ.
Conclusions
These findings indicate that PDGFRβ+ and Olig2+ cells contribute to the proliferative fraction following penetrating brain injuries, with evidence of pericyte migration. Dynamic changes in Cx43 in glial cell types with dpi suggest functional alterations during temporal stages of brain repair.]]></description><subject>Adolescent</subject><subject>Adult</subject><subject>Aged, 80 and over</subject><subject>Aquaporin 4</subject><subject>Brain - metabolism</subject><subject>Brain - pathology</subject><subject>Brain injury</subject><subject>Cell proliferation</subject><subject>Connexin 43</subject><subject>Cortex</subject><subject>Female</subject><subject>Glial fibrillary acidic protein</subject><subject>Glial Fibrillary Acidic Protein - metabolism</subject><subject>glial scar</subject><subject>Gliosis - metabolism</subject><subject>Gliosis - pathology</subject><subject>Glutamate-ammonia ligase</subject><subject>Glutamine</subject><subject>Head Injuries, Penetrating - metabolism</subject><subject>Head Injuries, Penetrating - pathology</subject><subject>Humans</subject><subject>Immunohistochemistry</subject><subject>Labeling</subject><subject>Localization</subject><subject>Male</subject><subject>Middle Aged</subject><subject>Nestin</subject><subject>Olig2 protein</subject><subject>Original</subject><subject>Pericytes</subject><subject>Pericytes - metabolism</subject><subject>Pericytes - pathology</subject><subject>progenitors</subject><subject>Receptor, Platelet-Derived Growth Factor beta - metabolism</subject><subject>Therapeutic applications</subject><subject>Traumatic brain injury</subject><subject>Young Adult</subject><issn>0305-1846</issn><issn>1365-2990</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><sourceid>24P</sourceid><sourceid>EIF</sourceid><recordid>eNp1kc1u1DAUhS0EosPAghdAltjAIq0d_8TeIFWFFqSqIH7Wlse5GTxK7GAnwIi36oP0mfAwQwVIeGHfa3_36FgHoceUHNOyToINx7QWTN9BC8qkqGqtyV20IIyIiiouj9CDnDeEENFIfR8dMSKZJE2zQD8-jHbycYJhjMn2uN0GO3iXcezwu5cX5-9vrjF8HxPk7GPAPuARknfbCTK2ocXr3pep7GzCXUzDTutABZhSacMar5L1u8vNnHwZK7Vt537KD9G9zvYZHh3OJfp0_urj2evq8u3Fm7PTy8pxznTVMrlSDYdOUGWpo0QS3tZOrzgoCtQqITvQnInWKaIoV8QxAUzUULeKl2qJXux1x3k1QOsgFGe9GZMfbNqaaL35-yX4z2YdvxrZyIbrpgg8Owik-GWGPJnBZwd9bwPEOZuaNpo1VAte0Kf_oJs4p1C-Z-pa14wJXrYler6nXIo5J-huzVBidpGaEqn5FWlhn_zp_pb8nWEBTvbAN9_D9v9K5ur0ai_5E8-mrY4</recordid><startdate>201910</startdate><enddate>201910</enddate><creator>Reeves, C.</creator><creator>Pradim‐Jardim, A.</creator><creator>Sisodiya, S. M.</creator><creator>Thom, M.</creator><creator>Liu, J. Y. W.</creator><general>Wiley Subscription Services, Inc</general><general>John Wiley and Sons Inc</general><scope>24P</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>7TK</scope><scope>K9.</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0001-7712-2629</orcidid></search><sort><creationdate>201910</creationdate><title>Spatiotemporal dynamics of PDGFRβ expression in pericytes and glial scar formation in penetrating brain injuries in adults</title><author>Reeves, C. ; Pradim‐Jardim, A. ; Sisodiya, S. M. ; Thom, M. ; Liu, J. Y. W.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4439-d36b874ef518a1c10604d2c9b4e81e1a856fe9435dc8081480c35e352e2d845e3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><topic>Adolescent</topic><topic>Adult</topic><topic>Aged, 80 and over</topic><topic>Aquaporin 4</topic><topic>Brain - metabolism</topic><topic>Brain - pathology</topic><topic>Brain injury</topic><topic>Cell proliferation</topic><topic>Connexin 43</topic><topic>Cortex</topic><topic>Female</topic><topic>Glial fibrillary acidic protein</topic><topic>Glial Fibrillary Acidic Protein - metabolism</topic><topic>glial scar</topic><topic>Gliosis - metabolism</topic><topic>Gliosis - pathology</topic><topic>Glutamate-ammonia ligase</topic><topic>Glutamine</topic><topic>Head Injuries, Penetrating - metabolism</topic><topic>Head Injuries, Penetrating - pathology</topic><topic>Humans</topic><topic>Immunohistochemistry</topic><topic>Labeling</topic><topic>Localization</topic><topic>Male</topic><topic>Middle Aged</topic><topic>Nestin</topic><topic>Olig2 protein</topic><topic>Original</topic><topic>Pericytes</topic><topic>Pericytes - metabolism</topic><topic>Pericytes - pathology</topic><topic>progenitors</topic><topic>Receptor, Platelet-Derived Growth Factor beta - metabolism</topic><topic>Therapeutic applications</topic><topic>Traumatic brain injury</topic><topic>Young Adult</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Reeves, C.</creatorcontrib><creatorcontrib>Pradim‐Jardim, A.</creatorcontrib><creatorcontrib>Sisodiya, S. M.</creatorcontrib><creatorcontrib>Thom, M.</creatorcontrib><creatorcontrib>Liu, J. Y. W.</creatorcontrib><collection>Wiley Online Library 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>Neurosciences Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Neuropathology and applied neurobiology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Reeves, C.</au><au>Pradim‐Jardim, A.</au><au>Sisodiya, S. M.</au><au>Thom, M.</au><au>Liu, J. Y. W.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Spatiotemporal dynamics of PDGFRβ expression in pericytes and glial scar formation in penetrating brain injuries in adults</atitle><jtitle>Neuropathology and applied neurobiology</jtitle><addtitle>Neuropathol Appl Neurobiol</addtitle><date>2019-10</date><risdate>2019</risdate><volume>45</volume><issue>6</issue><spage>609</spage><epage>627</epage><pages>609-627</pages><issn>0305-1846</issn><eissn>1365-2990</eissn><abstract><![CDATA[Aims
Understanding the spatiotemporal dynamics of reactive cell types following brain injury is important for future therapeutic interventions. We have previously used penetrating cortical injuries following intracranial recordings as a brain repair model to study scar‐forming nestin‐expressing cells. We now explore the relationship between nestin‐expressing cells, PDGFRβ+ pericytes and Olig2+ glia, including their proliferation and functional maturation.
Methods
In 32 cases, ranging from 3 to 461 days post injury (dpi), immunohistochemistry for PDGFRβ, nestin, GFAP, Olig2, MCM2, Aquaporin 4 (Aq4), Glutamine Synthetase (GS) and Connexin 43 (Cx43) was quantified for cell densities, labelling index (LI) and cellular co‐expression at the injury site compared to control regions.
Results
PDGFRβ labelling highlighted both pericytes and multipolar parenchymal cells. PDGFRβ LI and PDGFRβ+/MCM2+ cells significantly increased in injury Zones at 10–13 dpi with migration of pericytes away from vessels with increased co‐localization of PDGRFβ with nestin compared to control regions (P < 0.005). Olig2+/MCM2+ cell populations peaked at 13 dpi with significantly higher cell densities at injury sites than in control regions (P < 0.01) and decreasing with dpi (P < 0.05). Cx43 LI was reduced in acute injuries but increased with dpi (P < 0.05) showing significant cellular co‐localization with nestin and GFAP (P < 0.005 and P < 0.0001) but not PDGFRβ.
Conclusions
These findings indicate that PDGFRβ+ and Olig2+ cells contribute to the proliferative fraction following penetrating brain injuries, with evidence of pericyte migration. Dynamic changes in Cx43 in glial cell types with dpi suggest functional alterations during temporal stages of brain repair.]]></abstract><cop>England</cop><pub>Wiley Subscription Services, Inc</pub><pmid>30636077</pmid><doi>10.1111/nan.12539</doi><tpages>19</tpages><orcidid>https://orcid.org/0000-0001-7712-2629</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0305-1846 |
| ispartof | Neuropathology and applied neurobiology, 2019-10, Vol.45 (6), p.609-627 |
| issn | 0305-1846 1365-2990 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_6767497 |
| source | MEDLINE; Wiley Online Library Journals Frontfile Complete |
| subjects | Adolescent Adult Aged, 80 and over Aquaporin 4 Brain - metabolism Brain - pathology Brain injury Cell proliferation Connexin 43 Cortex Female Glial fibrillary acidic protein Glial Fibrillary Acidic Protein - metabolism glial scar Gliosis - metabolism Gliosis - pathology Glutamate-ammonia ligase Glutamine Head Injuries, Penetrating - metabolism Head Injuries, Penetrating - pathology Humans Immunohistochemistry Labeling Localization Male Middle Aged Nestin Olig2 protein Original Pericytes Pericytes - metabolism Pericytes - pathology progenitors Receptor, Platelet-Derived Growth Factor beta - metabolism Therapeutic applications Traumatic brain injury Young Adult |
| title | Spatiotemporal dynamics of PDGFRβ expression in pericytes and glial scar formation in penetrating brain injuries in adults |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-30T07%3A28%3A23IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Spatiotemporal%20dynamics%20of%20PDGFR%CE%B2%20expression%20in%20pericytes%20and%20glial%20scar%20formation%20in%20penetrating%20brain%20injuries%20in%20adults&rft.jtitle=Neuropathology%20and%20applied%20neurobiology&rft.au=Reeves,%20C.&rft.date=2019-10&rft.volume=45&rft.issue=6&rft.spage=609&rft.epage=627&rft.pages=609-627&rft.issn=0305-1846&rft.eissn=1365-2990&rft_id=info:doi/10.1111/nan.12539&rft_dat=%3Cproquest_pubme%3E2292335423%3C/proquest_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2292335423&rft_id=info:pmid/30636077&rfr_iscdi=true |