{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,28]],"date-time":"2026-02-28T04:29:13Z","timestamp":1772252953661,"version":"3.50.1"},"reference-count":46,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2021,9,9]],"date-time":"2021-09-09T00:00:00Z","timestamp":1631145600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100007155","name":"Medical Research Council","doi-asserted-by":"publisher","award":["MR\/S003045\/1"],"award-info":[{"award-number":["MR\/S003045\/1"]}],"id":[{"id":"10.13039\/501100007155","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100008731","name":"European Leukodystrophy Association","doi-asserted-by":"publisher","award":["ELA2017-015I4"],"award-info":[{"award-number":["ELA2017-015I4"]}],"id":[{"id":"10.13039\/501100008731","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Oligodendrocytes produce myelin, which provides insulation to axons and speeds up neuronal transmission. In ischaemic conditions, myelin is damaged, resulting in mental and physical disabilities. Recent evidence suggests that oligodendrocyte damage during ischaemia can be mediated by Transient Receptor Potential Ankyrin-1 (TRPA1), whose activation raises intracellular Ca2+ concentrations and damages compact myelin. Here, we show that TRPA1 is constitutively active in oligodendrocytes and the optic nerve, as the specific TRPA1 antagonist, A-967079, decreases basal oligodendrocyte Ca2+ concentrations and increases the size of the compound action potential (CAP). Conversely, TRPA1 agonists reduce the size of the optic nerve CAP in an A-967079-sensitive manner. These results indicate that glial TRPA1 regulates neuronal excitability in the white matter under physiological as well as pathological conditions. Importantly, we find that inhibition of TRPA1 prevents loss of CAPs during oxygen and glucose deprivation (OGD) and improves the recovery. TRPA1 block was effective when applied before, during, or after OGD, indicating that the TRPA1-mediated damage is occurring during both ischaemia and recovery, but importantly, that therapeutic intervention is possible after the ischaemic insult. These results indicate that TRPA1 has an important role in the brain, and that its block may be effective in treating many white matter diseases.<\/jats:p>","DOI":"10.3390\/ph14090909","type":"journal-article","created":{"date-parts":[[2021,9,9]],"date-time":"2021-09-09T21:36:58Z","timestamp":1631223418000},"page":"909","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Transient Receptor Potential Ankyrin-1 (TRPA1) Block Protects against Loss of White Matter Function during Ischaemia in the Mouse Optic Nerve"],"prefix":"10.3390","volume":"14","author":[{"given":"Wendy","family":"Lajoso","sequence":"first","affiliation":[{"name":"Wolfson Centre for Age-Related Diseases, Institute of Psychiatry, Psychology and Neuroscience, Guy\u2019s Campus, King\u2019s College London, London SE1 1UL, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Grace","family":"Flower","sequence":"additional","affiliation":[{"name":"Wolfson Centre for Age-Related Diseases, Institute of Psychiatry, Psychology and Neuroscience, Guy\u2019s Campus, King\u2019s College London, London SE1 1UL, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vincenzo","family":"Giacco","sequence":"additional","affiliation":[{"name":"Wolfson Centre for Age-Related Diseases, Institute of Psychiatry, Psychology and Neuroscience, Guy\u2019s Campus, King\u2019s College London, London SE1 1UL, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anjuli","family":"Kaul","sequence":"additional","affiliation":[{"name":"Wolfson Centre for Age-Related Diseases, Institute of Psychiatry, Psychology and Neuroscience, Guy\u2019s Campus, King\u2019s College London, London SE1 1UL, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Circe","family":"La Mache","sequence":"additional","affiliation":[{"name":"Wolfson Centre for Age-Related Diseases, Institute of Psychiatry, Psychology and Neuroscience, Guy\u2019s Campus, King\u2019s College London, London SE1 1UL, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andra","family":"Br\u0103ban","sequence":"additional","affiliation":[{"name":"Wolfson Centre for Age-Related Diseases, Institute of Psychiatry, Psychology and Neuroscience, Guy\u2019s Campus, King\u2019s College London, London SE1 1UL, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Angela","family":"Roxas","sequence":"additional","affiliation":[{"name":"Wolfson Centre for Age-Related Diseases, Institute of Psychiatry, Psychology and Neuroscience, Guy\u2019s Campus, King\u2019s College London, London SE1 1UL, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0168-8068","authenticated-orcid":false,"given":"Nicola B.","family":"Hamilton","sequence":"additional","affiliation":[{"name":"Wolfson Centre for Age-Related Diseases, Institute of Psychiatry, Psychology and Neuroscience, Guy\u2019s Campus, King\u2019s College London, London SE1 1UL, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,9,9]]},"reference":[{"key":"ref_1","first-page":"5160","article-title":"Clinical features of acute corpus callosum infarction patients","volume":"7","author":"Yang","year":"2014","journal-title":"Int. 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