{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T01:19:50Z","timestamp":1792631990375,"version":"4.5.0"},"reference-count":60,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2024,2,8]],"date-time":"2024-02-08T00:00:00Z","timestamp":1707350400000},"content-version":"vor","delay-in-days":7,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2024,2,1]],"date-time":"2024-02-01T00:00:00Z","timestamp":1706745600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R21AI121700"],"award-info":[{"award-number":["R21AI121700"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01AI050875"],"award-info":[{"award-number":["R01AI050875"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["RF1AG058603"],"award-info":[{"award-number":["RF1AG058603"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["CNS Neurosci Ther"],"published-print":{"date-parts":[[2024,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Rationale<\/jats:title>\n                    <jats:p>Numerous epidemiological studies have reported a link between low testosterone levels and an increased risk of cerebrovascular disease in men. However, there is ongoing controversy surrounding testosterone replacement therapy due to potential side effects. PBMT has been demonstrated to improve cerebrovascular function and promote testosterone synthesis in peripheral tissues. Despite this, the molecular mechanisms that could connect PBMT with testosterone and vascular function in the brain of photothrombosis (PT)\u2010induced stroke rats remain largely unknown.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We measured behavioral performance, cerebral blood flow (CBF), vascular permeability, and the expression of vascular\u2010associated and apoptotic proteins in PT\u2010induced stroke rats treated with flutamide and seven consecutive days of PBM treatment (350\u2009mW, 808\u2009nM, 2\u2009min\/day). To gain further insights into the mechanism of PBM on testosterone synthesis, we used testosterone synthesis inhibitors to study their effects on bEND.3 cells.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      We showed that PT stroke caused a decrease in cerebrovascular testosterone concentration, which was significantly increased by 7\u2010day PBMT (808\u2009nm, 350\u2009mW\/cm\n                      <jats:sup>2<\/jats:sup>\n                      , 42\u2009J\/cm\n                      <jats:sup>2<\/jats:sup>\n                      ). Furthermore, PBMT significantly increased cerebral blood flow (CBF) and the expression of vascular\u2010associated proteins, while inhibiting vascular permeability and reducing endothelial cell apoptosis. This ultimately mitigated behavioral deficits in PT stroke rats. Notably, treatment with the androgen receptor antagonist flutamide reversed the beneficial effects of PBMT. Cellular experiments confirmed that PBMT inhibited cell apoptosis and increased vascular\u2010associated protein expression in brain endothelial cell line (bEnd.3) subjected to oxygen\u2010glucose deprivation (OGD). However, these effects were inhibited by flutamide. Moreover, mechanistic studies revealed that PBMT\u2010induced testosterone synthesis in bEnd.3 cells was partly mediated by 17\u03b2\u2010hydroxysteroid dehydrogenase 5 (17\u03b2\u2010HSD5).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Our study provides evidence that PBMT attenuates cerebrovascular injury and behavioral deficits associated with testosterone\/AR following ischemic stroke. Our findings suggest that PBMT may be a promising alternative approach for managing cerebrovascular diseases.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/cns.14574","type":"journal-article","created":{"date-parts":[[2024,2,8]],"date-time":"2024-02-08T06:19:31Z","timestamp":1707373171000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Activation of\n                    <scp>testosterone\u2010androgen<\/scp>\n                    receptor mediates cerebrovascular protection by photobiomodulation treatment in photothrombosis\u2010induced stroke rats"],"prefix":"10.1111","volume":"30","author":[{"given":"Yu","family":"Feng","sequence":"first","affiliation":[{"name":"Department of Neurology Louisiana State University Health Sciences Center  Shreveport Louisiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhihai","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Neurology Louisiana State University Health Sciences Center  Shreveport Louisiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaohui","family":"Ma","sequence":"additional","affiliation":[{"name":"Department of Neurology Louisiana State University Health Sciences Center  Shreveport Louisiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuemei","family":"Zong","sequence":"additional","affiliation":[{"name":"Department of Neurology Louisiana State University Health Sciences Center  Shreveport Louisiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Celeste Yin\u2010Chieh","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Neurology Louisiana State University Health Sciences Center  Shreveport Louisiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6099-8333","authenticated-orcid":false,"given":"Reggie Hui\u2010Chao","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Neurology Louisiana State University Health Sciences Center  Shreveport Louisiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hung Wen","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Neurology Louisiana State University Health Sciences Center  Shreveport Louisiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael R.","family":"Hamblin","sequence":"additional","affiliation":[{"name":"Wellman Center for Photomedicine Massachusetts General Hospital  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6499-7952","authenticated-orcid":false,"given":"Quanguang","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Neurology Louisiana State University Health Sciences Center  Shreveport Louisiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,2,8]]},"reference":[{"key":"e_1_2_9_2_1","first-page":"600","article-title":"Rehabilitation after stroke","volume":"108","author":"Knecht S","year":"2011","journal-title":"Dtsch Arztebl Int"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0b013e318270401d"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.120.030803"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1177\/2047487318778346"},{"key":"e_1_2_9_6_1","article-title":"The Association of Serum Testosterone Levels with Recurrence and Mortality after Acute Ischemic Stroke in males","volume":"13","author":"Ho CH","year":"2019","journal-title":"Am J Mens Health"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainres.2014.02.028"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainres.2005.02.078"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1124\/pr.57.2.4"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.7150\/thno.51573"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1159\/000509218"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13293-020-00309-4"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2002-020632"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1177\/0271678X16683961"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbamcr.2017.05.006"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.jcbfm.9600483"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/jcbfm.2009.60"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.20352"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12035-021-02496-6"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.expneurol.2017.10.013"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.7150\/thno.49672"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.3233\/JAD-210386"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10103-016-1904-0"},{"key":"e_1_2_9_24_1","first-page":"28","article-title":"The effects of low level laser therapy (LLLT) on the testis in elevating serum testosterone level in rats","volume":"24","author":"Jin\u2010Chul Ahn Y\u2010HK","year":"2012","journal-title":"Biomed Res"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0039-128X(96)00174-2"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1021\/jm201547v"},{"key":"e_1_2_9_27_1","first-page":"87","article-title":"Effect of low intensity laser beam on steroid dehydrogenase activity and steroid hormone production in cultured porcine granulosa cells","volume":"21","author":"Gregoraszczuk E","year":"1983","journal-title":"Folia Histochem Cytochem (Krakow)"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yhbeh.2019.01.002"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mce.2013.12.019"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41380-021-01088-z"},{"key":"e_1_2_9_31_1","first-page":"1","article-title":"Protein arginine methyltransferase 4 modulates nitric oxide synthase uncoupling and cerebral blood flow in Alzheimer's disease","volume":"2022","author":"Clemons GA","year":"2022","journal-title":"J Cell Physiol"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41596-019-0212-0"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12987-020-00182-8"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms19092793"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.201404140"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.78517"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.18632\/aging.103584"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2012.00089"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.ATV.16.6.749"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.1089\/andro.2021.0023"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.1002\/cnr2.1241"},{"key":"e_1_2_9_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2020.117767"},{"key":"e_1_2_9_43_1","doi-asserted-by":"publisher","DOI":"10.3389\/fneur.2020.594672"},{"key":"e_1_2_9_44_1","doi-asserted-by":"publisher","DOI":"10.1002\/advs.202104629"},{"issue":"10","key":"e_1_2_9_45_1","first-page":"564","article-title":"Photobiomodulation mitigates cerebrovascular leakage induced by the parkinsonian neurotoxin MPTP","volume":"9","author":"San Miguel M","year":"2019","journal-title":"Biomol Ther"},{"key":"e_1_2_9_46_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2020.605398"},{"key":"e_1_2_9_47_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms23126413"},{"key":"e_1_2_9_48_1","doi-asserted-by":"publisher","DOI":"10.4103\/1673-5374.276328"},{"key":"e_1_2_9_49_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jphotobiol.2022.112590"},{"key":"e_1_2_9_50_1","doi-asserted-by":"publisher","DOI":"10.21037\/atm-21-5619"},{"key":"e_1_2_9_51_1","doi-asserted-by":"publisher","DOI":"10.1111\/jon.13023"},{"issue":"3","key":"e_1_2_9_52_1","first-page":"274","article-title":"Experimental and clinical applications of red and near\u2010infrared Photobiomodulation on endothelial dysfunction: a review","volume":"9","author":"Colombo E","year":"2021","journal-title":"Biomedicine"},{"key":"e_1_2_9_53_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-019-1716-9"},{"key":"e_1_2_9_54_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12017-019-08569-z"},{"key":"e_1_2_9_55_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12031-018-1121-3"},{"key":"e_1_2_9_56_1","doi-asserted-by":"publisher","DOI":"10.1530\/JOE-11-0441"},{"key":"e_1_2_9_57_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2265.2007.03036.x"},{"key":"e_1_2_9_58_1","first-page":"225","article-title":"Testosterone and adult neurogenesis","volume":"10","author":"Spritzer MD","year":"2020","journal-title":"Biomol Ther"},{"key":"e_1_2_9_59_1","doi-asserted-by":"publisher","DOI":"10.1677\/erc.1.01048"},{"key":"e_1_2_9_60_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11010-013-1900-7"},{"key":"e_1_2_9_61_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.109.848911"}],"updated-by":[{"DOI":"10.1111\/cns.14869","type":"correction","label":"Correction","source":"publisher","updated":{"date-parts":[[2024,7,16]],"date-time":"2024-07-16T00:00:00Z","timestamp":1721088000000}}],"container-title":["CNS Neuroscience &amp; Therapeutics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cns.14574","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/cns.14574","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cns.14574","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,14]],"date-time":"2026-02-14T14:20:49Z","timestamp":1771078849000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/cns.14574"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,2]]},"references-count":60,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2024,2]]}},"alternative-id":["10.1111\/cns.14574"],"URL":"https:\/\/doi.org\/10.1111\/cns.14574","archive":["Portico"],"relation":{},"ISSN":["1755-5930","1755-5949"],"issn-type":[{"value":"1755-5930","type":"print"},{"value":"1755-5949","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,2]]},"assertion":[{"value":"2023-10-06","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-12-06","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-02-08","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e14574"}}