{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,16]],"date-time":"2026-04-16T06:45:28Z","timestamp":1776321928376,"version":"3.50.1"},"reference-count":53,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2017,3,3]],"date-time":"2017-03-03T00:00:00Z","timestamp":1488499200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81470656"],"award-info":[{"award-number":["81470656"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Journal of Neurochemistry"],"published-print":{"date-parts":[[2017,5]]},"abstract":"Abstract<\/jats:title>Adding a free radical\u2010scavenging nitrone moiety on tetramethylpyrazine, we have previously synthesized a chemical named 2\u2010[[(1,1\u2010dimethylethyl)oxidoimino]\u2010methyl]\u20103,5,6\u2010trimethylpyrazine (tetramethylpyrazine nitrone, or TBN<\/jats:styled-content>) and proved its neuroprotective effect but with limited understanding of its mechanism. Here we ask if TBN<\/jats:styled-content> protects retinal ganglion cells (RGC<\/jats:styled-content>s) against excitotoxicity induced by NMDA<\/jats:styled-content> and explore the underlying mechanism. NMDA<\/jats:styled-content> was intravitreally injected to induce RGC<\/jats:styled-content> injury in rats, followed by daily intraperitoneal administrations of TBN<\/jats:styled-content>. Measurements of TBN<\/jats:styled-content> concentration at different times after intraperitoneal administration showed that more than 200\u00a0\u03bcM TBN<\/jats:styled-content> reached the aqueous humor quickly. Then RGC<\/jats:styled-content>s\u2019 survival was evaluated by quantifying Brn3\u2010positive cells, and retinal functions were examined by electroretinogram and visual behaviors. TBN<\/jats:styled-content> significantly increased the survival of RGC<\/jats:styled-content>s after NMDA<\/jats:styled-content> insult, recovered the amplitude of photopic negative responses to flash, and restored the visual behavior. Furthermore, TBN<\/jats:styled-content> inhibited the apoptotic process, as indicated by the elevated ratios of cleaved caspase\u20103\/caspase\u20103 and of Bax\/Bcl\u20102, and decreased the level of reactive oxygen species. Moreover, TBN<\/jats:styled-content> reduced RGC<\/jats:styled-content>'s calcium overload induced by NMDA<\/jats:styled-content> or by KC<\/jats:styled-content>l. Whole\u2010cell patch recording from RGC<\/jats:styled-content>s further showed that TBN<\/jats:styled-content> slightly but significantly inhibited L\u2010type calcium channels, but had little effect on T\u2010type calcium channel or NMDA<\/jats:styled-content>\u2010, \u03b1\u2010amino\u20103\u2010hydroxy\u20105\u2010methyl\u20104\u2010isoxazolepropionic acid(AMPA)\u2010induced current. Thus our data indicate that TBN<\/jats:styled-content> alleviates NMDA<\/jats:styled-content>\u2010elicited injury of rat RGC<\/jats:styled-content>s both morphologically and functionally, possibly by inhibiting the L\u2010type calcium channel thus reducing Ca2+<\/jats:sup> overload and by directly scavenging free radicals. Therefore, TBN<\/jats:styled-content> may be a novel candidate for treating excitotoxicity\u2010related visual disorders such as glaucoma.<\/jats:p><\/jats:sec>\nimage<\/jats:alt-text><\/jats:graphic><\/jats:boxed-text>\n<\/jats:p><\/jats:sec>","DOI":"10.1111\/jnc.13970","type":"journal-article","created":{"date-parts":[[2017,2,3]],"date-time":"2017-02-03T20:35:35Z","timestamp":1486154135000},"page":"373-386","source":"Crossref","is-referenced-by-count":24,"title":["Tetramethylpyrazine nitrone protects retinal ganglion cells against N<\/i>\u2010methyl\u2010d<\/scp>\u2010aspartate\u2010induced excitotoxicity"],"prefix":"10.1111","volume":"141","author":[{"given":"Xiaopeng","family":"Luo","sequence":"first","affiliation":[{"name":"GHM Institute of CNS Regeneration Jinan University Guangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yankun","family":"Yu","sequence":"additional","affiliation":[{"name":"GHM Institute of CNS Regeneration Jinan University Guangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zongqin","family":"Xiang","sequence":"additional","affiliation":[{"name":"GHM Institute of CNS Regeneration Jinan University Guangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Huisu","family":"Wu","sequence":"additional","affiliation":[{"name":"Institute of New Drug Research and Guangzhou Key Laboratory of Innovative Chemical Drug Research in Cardio\u2010cerebrovascular Diseases Jinan University Guangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Seeram","family":"Ramakrishna","sequence":"additional","affiliation":[{"name":"GHM Institute of CNS Regeneration Jinan University Guangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuqiang","family":"Wang","sequence":"additional","affiliation":[{"name":"Institute of New Drug Research and Guangzhou Key Laboratory of Innovative Chemical Drug Research in Cardio\u2010cerebrovascular Diseases Jinan University Guangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kwok\u2010Fai","family":"So","sequence":"additional","affiliation":[{"name":"GHM Institute of CNS Regeneration Jinan University Guangzhou China"},{"name":"Co\u2010Innovation Center of Neuroregeneration Nantong University Jiangsu China"},{"name":"Joint International Research Laboratory of CNS Regeneration Ministry of Education of PRC Guangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zaijun","family":"Zhang","sequence":"additional","affiliation":[{"name":"Institute of New Drug Research and Guangzhou Key Laboratory of Innovative Chemical Drug Research in Cardio\u2010cerebrovascular Diseases Jinan University Guangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ying","family":"Xu","sequence":"additional","affiliation":[{"name":"GHM Institute of CNS Regeneration Jinan University Guangzhou China"},{"name":"Co\u2010Innovation Center of Neuroregeneration Nantong University Jiangsu China"},{"name":"Joint International Research Laboratory of CNS Regeneration Ministry of Education of PRC Guangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2017,3,3]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1001\/archopht.1997.01100160331011"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.3390\/toxins8030070"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/0014-2999(89)90385-3"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2015.05.088"},{"key":"e_1_2_7_6_1","first-page":"870","article-title":"Ischemic stroke treated with Ligusticum chuanxiong","volume":"105","author":"Chen K. 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