{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,23]],"date-time":"2026-07-23T23:22:58Z","timestamp":1784848978867,"version":"3.55.0"},"reference-count":41,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2023,3,2]],"date-time":"2023-03-02T00:00:00Z","timestamp":1677715200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Sight Glaucoma UK Small","award":["U\/24GUK"],"award-info":[{"award-number":["U\/24GUK"]}]},{"name":"Welsh Clinical Academic Track programme"},{"name":"Tweedy Bequest"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,3,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>In humans and other primates, blood platelets contain high concentrations of brain-derived neurotrophic factor due to the expression of the BDNF gene in megakaryocytes. By contrast, mice, typically used to investigate the impact of CNS lesions, have no demonstrable levels of brain-derived neurotrophic factor in platelets, and their megakaryocytes do not transcribe significant levels of the Bdnf gene. Here, we explore potential contributions of platelet brain-derived neurotrophic factor with two well-established CNS lesion models, using \u2018humanized\u2019 mice engineered to express the Bdnf gene under the control of a megakaryocyte-specific promoter. Retinal explants prepared from mice containing brain-derived neurotrophic factor in platelets were labelled using DiOlistics and the dendritic integrity of retinal ganglion cells assessed after 3 days by Sholl analysis. The results were compared with retinas of wild-type animals and with wild-type explants supplemented with saturating concentrations of brain-derived neurotrophic factor or the tropomyosin kinase B antibody agonist, ZEB85. An optic nerve crush was also performed, and the dendrites of retinal ganglion cells similarly assessed 7-day post-injury, comparing the results of mice containing brain-derived neurotrophic factor in platelets with wild-type animals. In mice engineered to contain brain-derived neurotrophic factor in platelets, the mean serum brain-derived neurotrophic factor levels were 25.74 \u00b1 11.36\u2005ng\/mL for homozygous and 17.02 \u00b1 6.44\u2005ng\/mL for heterozygous mice, close to those determined in primates. Retinal explants from these animals showed robust preservation of dendrite complexity, similar to that seen with wild-type explants incubated with medium supplemented with brain-derived neurotrophic factor or the tropomyosin receptor kinase B antibody agonist, ZEB85. The Sholl areas under curve were 1811 \u00b1 258, 1776 \u00b1 435 and 1763 \u00b1 256 versus 1406 \u00b1 315 in the wild-type control group (P \u2264 0.001). Retinal ganglion cell survival based on cell counts was similar in all four groups, showing \u223c15% loss. A robust neuroprotective effect was also observed following optic nerve crush when assessing the dendrites of the retinal ganglion cells in the transgenic mouse, with Sholl area under the curve significantly higher compared to wild-type (2667 \u00b1 690 and 1921 \u00b1 392, P = 0.026), with no significant difference in the contralateral eye controls. Repeat experiments found no difference in cell survival, with both showing \u223c50% loss. These results indicate that platelet brain-derived neurotrophic factor has a strong neuroprotective effect on the dendrite complexity of retinal ganglion cells in both an ex vivo and in vivo model, suggesting that platelet brain-derived neurotrophic factor is likely to be a significant neuroprotective factor in primates.<\/jats:p>","DOI":"10.1093\/braincomms\/fcad046","type":"journal-article","created":{"date-parts":[[2023,3,3]],"date-time":"2023-03-03T05:22:07Z","timestamp":1677820927000},"source":"Crossref","is-referenced-by-count":21,"title":["Brain-derived neurotrophic factor released from blood platelets prevents dendritic atrophy of lesioned adult central nervous system neurons"],"prefix":"10.1093","volume":"5","author":[{"given":"Andrew","family":"Want","sequence":"first","affiliation":[{"name":"School of Optometry and Vision Sciences, Cardiff University , Cardiff CF24 4HQ , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinsheng","family":"Nan","sequence":"additional","affiliation":[{"name":"School of Bioscience, Cardiff University , Cardiff CF10 3AX , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eirini","family":"Kokkali","sequence":"additional","affiliation":[{"name":"School of Optometry and Vision Sciences, Cardiff University , Cardiff CF24 4HQ , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yves-Alain","family":"Barde","sequence":"additional","affiliation":[{"name":"School of Bioscience, Cardiff University , Cardiff CF10 3AX , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James E","family":"Morgan","sequence":"additional","affiliation":[{"name":"School of Optometry and Vision Sciences, Cardiff University , Cardiff CF24 4HQ , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2023,3,2]]},"reference":[{"key":"2023032212284287600_","doi-asserted-by":"crossref","first-page":"549","DOI":"10.1002\/j.1460-2075.1982.tb01207.x","article-title":"Purification of a new neurotrophic factor from mammalian brain","volume":"1","author":"Barde","year":"1982","journal-title":"EMBO J"},{"key":"2023032212284287600_","doi-asserted-by":"crossref","first-page":"296","DOI":"10.1016\/0012-1606(89)90256-X","article-title":"The survival of chick retinal ganglion cells in response to brain-derived neurotrophic factor depends on their embryonic age","volume":"136","author":"Rodriguez-T\u00e9bar","year":"1989","journal-title":"Dev Biol."},{"key":"2023032212284287600_","doi-asserted-by":"crossref","first-page":"753","DOI":"10.1038\/360753a0","article-title":"Brain-derived neurotrophic factor rescues spinal motor neurons from axotomy-induced cell 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