{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T06:06:27Z","timestamp":1792649187370,"version":"4.5.0"},"reference-count":50,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2019,4,2]],"date-time":"2019-04-02T00:00:00Z","timestamp":1554163200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000272","name":"National Institute for Health Research","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000272","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Neuropathology Appl Neurobio"],"published-print":{"date-parts":[[2019,10]]},"abstract":"<jats:sec><jats:title>Aims<\/jats:title><jats:p>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\u2010forming nestin\u2010expressing cells. We now explore the relationship between nestin\u2010expressing cells, <jats:styled-content style=\"fixed-case\">PDGFR<\/jats:styled-content>\u03b2<jats:sup>+<\/jats:sup> pericytes and Olig2<jats:sup>+<\/jats:sup> glia, including their proliferation and functional maturation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>In 32 cases, ranging from 3 to 461\u00a0days post injury (dpi), immunohistochemistry for <jats:styled-content style=\"fixed-case\">PDGFR<\/jats:styled-content>\u03b2, nestin, <jats:styled-content style=\"fixed-case\">GFAP<\/jats:styled-content>, Olig2, <jats:styled-content style=\"fixed-case\">MCM<\/jats:styled-content>2, Aquaporin 4 (Aq4), Glutamine Synthetase (<jats:styled-content style=\"fixed-case\">GS<\/jats:styled-content>) and Connexin 43 (Cx43) was quantified for cell densities, labelling index (<jats:styled-content style=\"fixed-case\">LI<\/jats:styled-content>) and cellular co\u2010expression at the injury site compared to control regions.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p><jats:styled-content style=\"fixed-case\">PDGFR<\/jats:styled-content>\u03b2 labelling highlighted both pericytes and multipolar parenchymal cells. <jats:styled-content style=\"fixed-case\">PDGFR<\/jats:styled-content>\u03b2 <jats:styled-content style=\"fixed-case\">LI<\/jats:styled-content> and <jats:styled-content style=\"fixed-case\">PDGFR<\/jats:styled-content>\u03b2<jats:sup>+<\/jats:sup>\/<jats:styled-content style=\"fixed-case\">MCM<\/jats:styled-content>2<jats:sup>+<\/jats:sup> cells significantly increased in injury Zones at 10\u201313\u00a0dpi with migration of pericytes away from vessels with increased co\u2010localization of <jats:styled-content style=\"fixed-case\">PDGRF<\/jats:styled-content>\u03b2 with nestin compared to control regions (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.005). Olig2<jats:sup>+<\/jats:sup>\/<jats:styled-content style=\"fixed-case\">MCM<\/jats:styled-content>2<jats:sup>+<\/jats:sup> cell populations peaked at 13\u00a0dpi with significantly higher cell densities at injury sites than in control regions (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.01) and decreasing with dpi (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.05). Cx43 <jats:styled-content style=\"fixed-case\">LI<\/jats:styled-content> was reduced in acute injuries but increased with dpi (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.05) showing significant cellular co\u2010localization with nestin and <jats:styled-content style=\"fixed-case\">GFAP<\/jats:styled-content> (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.005 and <jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.0001) but not <jats:styled-content style=\"fixed-case\">PDGFR<\/jats:styled-content>\u03b2.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>These findings indicate that <jats:styled-content style=\"fixed-case\">PDGFR<\/jats:styled-content>\u03b2<jats:sup>+<\/jats:sup> and Olig2<jats:sup>+<\/jats:sup> 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.<\/jats:p><\/jats:sec>","DOI":"10.1111\/nan.12539","type":"journal-article","created":{"date-parts":[[2019,1,12]],"date-time":"2019-01-12T16:53:33Z","timestamp":1547312013000},"page":"609-627","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["Spatiotemporal dynamics of <scp>PDGFR<\/scp>\u03b2 expression in pericytes and glial scar formation in penetrating brain injuries in adults"],"prefix":"10.1111","volume":"45","author":[{"given":"C.","family":"Reeves","sequence":"first","affiliation":[{"name":"Department of Clinical and Experimental Epilepsy UCL Queen Square Institute of Neurology Queen Square London"},{"name":"Department of Neuropathology UCL Queen Square Institute of Neurology Queen Square London"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.","family":"Pradim\u2010Jardim","sequence":"additional","affiliation":[{"name":"Department of Clinical and Experimental Epilepsy UCL Queen Square Institute of Neurology Queen Square London"},{"name":"Department of Neurology and Neurosurgery Universidade Federal de Sao Paulo UNIFESP Sao Paulo\/SP Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S. M.","family":"Sisodiya","sequence":"additional","affiliation":[{"name":"Department of Clinical and Experimental Epilepsy UCL Queen Square Institute of Neurology Queen Square London"},{"name":"Chalfont Centre for Epilepsy Chesham Lane Chalfont St Peter Bucks SL9 0RJ UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7712-2629","authenticated-orcid":false,"given":"M.","family":"Thom","sequence":"additional","affiliation":[{"name":"Department of Clinical and Experimental Epilepsy UCL Queen Square Institute of Neurology Queen Square London"},{"name":"Department of Neuropathology UCL Queen Square Institute of Neurology Queen Square London"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. Y. W.","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Clinical and Experimental Epilepsy UCL Queen Square Institute of Neurology Queen Square London"},{"name":"Department of Neuropathology UCL Queen Square Institute of Neurology Queen Square London"},{"name":"School of life Sciences University of Westminster London W1W 6UW UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2019,4,2]]},"reference":[{"key":"e_1_2_8_2_1","first-page":"119","article-title":"Glial cells in non\u2010germinal territories: insights into their stem\/progenitor properties in the intact and injured nervous tissue","volume":"148","author":"Boda E","year":"2010","journal-title":"Arch Ital Biol"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00041.2013"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.expneurol.2015.03.020"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12035-018-1008-x"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/ejn.12548"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/aws147"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.2121-13.2013"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/glia.23211"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0035577"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11481-014-9557-x"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/nn.2946"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1387\/ijdb.103167dr"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/nn.4288"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.05-4944fje"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.devcel.2011.07.001"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1186\/1750-1326-5-32"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/jemt.1060"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.jcbfm.9600272"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1186\/2001-1326-1-30"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1750-3639.2009.00295.x"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1002\/glia.23094"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.stem.2016.12.006"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a022434"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11481-012-9352-5"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2014.11.048"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2013.00088"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbamem.2017.08.014"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1002\/glia.22824"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1002\/glia.20094"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1002\/cyto.a.20896"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.131.2.453"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1006\/exnr.1999.7222"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1006\/mvre.2000.2244"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1203165"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.1038\/jcbfm.2012.187"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.1186\/scrt512"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep13497"},{"key":"e_1_2_8_39_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.3953-16.2017"},{"key":"e_1_2_8_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainresbull.2017.06.020"},{"key":"e_1_2_8_41_1","doi-asserted-by":"publisher","DOI":"10.1111\/epi.12143"},{"key":"e_1_2_8_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2015.07.090"},{"key":"e_1_2_8_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2014.07.010"},{"key":"e_1_2_8_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neulet.2015.04.047"},{"key":"e_1_2_8_45_1","doi-asserted-by":"publisher","DOI":"10.1093\/jnen\/nlw025"},{"key":"e_1_2_8_46_1","doi-asserted-by":"publisher","DOI":"10.3233\/RNN-160675"},{"key":"e_1_2_8_47_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2015.04.035"},{"key":"e_1_2_8_48_1","doi-asserted-by":"publisher","DOI":"10.1038\/aps.2015.39"},{"key":"e_1_2_8_49_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0047311"},{"key":"e_1_2_8_50_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0187-17.2017"},{"key":"e_1_2_8_51_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.201700699R"}],"container-title":["Neuropathology and Applied Neurobiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fnan.12539","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/nan.12539","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/nan.12539","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/nan.12539","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,10]],"date-time":"2023-09-10T04:07:00Z","timestamp":1694318820000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/nan.12539"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,4,2]]},"references-count":50,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2019,10]]}},"alternative-id":["10.1111\/nan.12539"],"URL":"https:\/\/doi.org\/10.1111\/nan.12539","archive":["Portico"],"relation":{},"ISSN":["0305-1846","1365-2990"],"issn-type":[{"value":"0305-1846","type":"print"},{"value":"1365-2990","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,4,2]]},"assertion":[{"value":"2018-05-23","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-10-17","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-04-02","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}