{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,18]],"date-time":"2026-06-18T10:10:57Z","timestamp":1781777457401,"version":"3.54.5"},"reference-count":36,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"3","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Stroke"],"published-print":{"date-parts":[[2019,3]]},"abstract":"<jats:sec>\n            <jats:title>Background and Purpose\u2014<\/jats:title>\n            <jats:p>Stroke is a major public health concern worldwide. Although clinical treatments have improved in the acute period after stroke, long-term therapeutics remain limited to physical rehabilitation in the delayed phase. This study is aimed to determine whether nNOS (neuronal NO synthase)-CAPON (carboxy-terminal postsynaptic density-95\/discs large\/zona occludens-1 ligand of nNOS) interaction may serve as a new therapeutic target in the delayed phase for stroke recovery.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods\u2014<\/jats:title>\n            <jats:p>Photothrombotic stroke and transient middle cerebral artery occlusion were induced in mice. Adeno-associated virus (AAV)-cytomegalovirus (CMV)-CAPON-125C-GFP (green fluorescent protein)-3Flag and the other 2 drugs (Tat-CAPON-12C and ZLc-002) were microinjected into the peri-infarct cortex immediately and 4 to 10 days after photothrombotic stroke, respectively. ZLc-002 was also systemically injected 4 to 10 days after transient middle cerebral artery occlusion. Grid-walking task and cylinder task were conducted to assess motor function. Western blotting, immunohistochemistry, Golgi staining, and electrophysiology recordings were performed to uncover the mechanisms.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results\u2014<\/jats:title>\n            <jats:p>Stroke increased nNOS-CAPON association in the peri-infarct cortex in the delayed period. Inhibiting the ischemia-induced nNOS-CAPON association substantially decreased the number of foot faults in the grid-walking task and forelimb asymmetry in the cylinder task, suggesting the promotion of functional recovery from stroke. Moreover, dissociating nNOS-CAPON significantly facilitated dendritic remodeling and synaptic transmission, indicated by increased dendritic spine density, dendritic branching, and length and miniature excitatory postsynaptic current frequency but did not affect stroke-elicited neuronal loss, infarct size, or cerebral edema, suggesting that nNOS-CAPON interaction may function via regulating structural neuroplasticity, rather than neuroprotection. Furthermore, ZLc-002 reversed the transient middle cerebral artery occlusion\u2013induced impairment of motor function.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions\u2014<\/jats:title>\n            <jats:p>Our results reveal that nNOS-CAPON coupling can serve as a novel pharmacological target for functional restoration after stroke.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/strokeaha.118.022647","type":"journal-article","created":{"date-parts":[[2019,2,7]],"date-time":"2019-02-07T10:03:06Z","timestamp":1549533786000},"page":"728-737","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":31,"title":["Dissociating nNOS (Neuronal NO Synthase)-CAPON (Carboxy-Terminal Postsynaptic Density-95\/Discs Large\/Zona Occludens-1 Ligand of nNOS) Interaction Promotes Functional Recovery After Stroke via Enhanced Structural Neuroplasticity"],"prefix":"10.1161","volume":"50","author":[{"given":"Huan-Yu","family":"Ni","sequence":"first","affiliation":[{"name":"From the Institution of Stem Cells and Neuroregeneration (H.-Y.N., Y.-X.S., Y.-H.L., B.C., D.-L.W., Y.Z., J.D., H.-Y.L., K.X., T.-Y.L., L.C., H.-Y.W., C.-X.L., D.-Y.Z.), Nanjing Medical University, China"},{"name":"Department of Pharmacology, School of Pharmacy (H.-Y.N., Y.-X.S., Y.-H.L., B.C., D.-L.W., Y.Z., J.D., H.-Y.L., K.X., T.-Y.L., L.C., H.-Y.W., C.-X.L., D.-Y.Z.), Nanjing Medical University, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi-Xuan","family":"Song","sequence":"additional","affiliation":[{"name":"From the Institution of Stem Cells and Neuroregeneration (H.-Y.N., Y.-X.S., Y.-H.L., B.C., D.-L.W., Y.Z., J.D., H.-Y.L., K.X., T.-Y.L., L.C., H.-Y.W., C.-X.L., D.-Y.Z.), Nanjing Medical University, China"},{"name":"Department of Pharmacology, School of Pharmacy (H.-Y.N., Y.-X.S., Y.-H.L., B.C., D.-L.W., Y.Z., J.D., H.-Y.L., K.X., T.-Y.L., L.C., H.-Y.W., C.-X.L., D.-Y.Z.), Nanjing Medical University, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu-Hui","family":"Lin","sequence":"additional","affiliation":[{"name":"From the Institution of Stem Cells and Neuroregeneration (H.-Y.N., Y.-X.S., Y.-H.L., B.C., D.-L.W., Y.Z., J.D., H.-Y.L., K.X., T.-Y.L., L.C., H.-Y.W., C.-X.L., D.-Y.Z.), Nanjing Medical University, China"},{"name":"Department of Pharmacology, School of Pharmacy (H.-Y.N., Y.-X.S., Y.-H.L., B.C., D.-L.W., Y.Z., J.D., H.-Y.L., K.X., T.-Y.L., L.C., H.-Y.W., C.-X.L., D.-Y.Z.), Nanjing Medical University, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bo","family":"Cao","sequence":"additional","affiliation":[{"name":"From the Institution of Stem Cells and Neuroregeneration (H.-Y.N., Y.-X.S., Y.-H.L., B.C., D.-L.W., Y.Z., J.D., H.-Y.L., K.X., T.-Y.L., L.C., H.-Y.W., C.-X.L., D.-Y.Z.), Nanjing Medical University, China"},{"name":"Department of Pharmacology, School of Pharmacy (H.-Y.N., Y.-X.S., Y.-H.L., B.C., D.-L.W., Y.Z., J.D., H.-Y.L., K.X., T.-Y.L., L.C., H.-Y.W., C.-X.L., D.-Y.Z.), Nanjing Medical University, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dong-Liang","family":"Wang","sequence":"additional","affiliation":[{"name":"From the Institution of Stem Cells and Neuroregeneration (H.-Y.N., Y.-X.S., Y.-H.L., B.C., D.-L.W., Y.Z., J.D., H.-Y.L., K.X., T.-Y.L., L.C., H.-Y.W., C.-X.L., D.-Y.Z.), Nanjing Medical University, China"},{"name":"Department of Pharmacology, School of Pharmacy (H.-Y.N., Y.-X.S., Y.-H.L., B.C., D.-L.W., Y.Z., J.D., H.-Y.L., K.X., T.-Y.L., L.C., H.-Y.W., C.-X.L., D.-Y.Z.), Nanjing Medical University, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Zhang","sequence":"additional","affiliation":[{"name":"From the Institution of Stem Cells and Neuroregeneration (H.-Y.N., Y.-X.S., Y.-H.L., B.C., D.-L.W., Y.Z., J.D., H.-Y.L., K.X., T.-Y.L., L.C., H.-Y.W., C.-X.L., D.-Y.Z.), Nanjing Medical University, China"},{"name":"Department of Pharmacology, School of Pharmacy (H.-Y.N., Y.-X.S., Y.-H.L., B.C., D.-L.W., Y.Z., J.D., H.-Y.L., K.X., T.-Y.L., L.C., H.-Y.W., C.-X.L., D.-Y.Z.), Nanjing Medical University, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian","family":"Dong","sequence":"additional","affiliation":[{"name":"From the Institution of Stem Cells and Neuroregeneration (H.-Y.N., Y.-X.S., Y.-H.L., B.C., D.-L.W., Y.Z., J.D., H.-Y.L., K.X., T.-Y.L., L.C., H.-Y.W., C.-X.L., D.-Y.Z.), Nanjing Medical University, China"},{"name":"Department of Pharmacology, School of Pharmacy (H.-Y.N., Y.-X.S., Y.-H.L., B.C., D.-L.W., Y.Z., J.D., H.-Y.L., K.X., T.-Y.L., L.C., H.-Y.W., C.-X.L., D.-Y.Z.), Nanjing Medical University, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hai-Ying","family":"Liang","sequence":"additional","affiliation":[{"name":"From the Institution of Stem Cells and Neuroregeneration (H.-Y.N., Y.-X.S., Y.-H.L., B.C., D.-L.W., Y.Z., J.D., H.-Y.L., K.X., T.-Y.L., L.C., H.-Y.W., C.-X.L., D.-Y.Z.), Nanjing Medical University, China"},{"name":"Department of Pharmacology, School of Pharmacy (H.-Y.N., Y.-X.S., Y.-H.L., B.C., D.-L.W., Y.Z., J.D., H.-Y.L., K.X., T.-Y.L., L.C., H.-Y.W., C.-X.L., D.-Y.Z.), Nanjing Medical University, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ke","family":"Xu","sequence":"additional","affiliation":[{"name":"From the Institution of Stem Cells and Neuroregeneration (H.-Y.N., Y.-X.S., Y.-H.L., B.C., D.-L.W., Y.Z., J.D., H.-Y.L., K.X., T.-Y.L., L.C., H.-Y.W., C.-X.L., D.-Y.Z.), Nanjing Medical University, China"},{"name":"Department of Pharmacology, School of Pharmacy (H.-Y.N., Y.-X.S., Y.-H.L., B.C., D.-L.W., Y.Z., J.D., H.-Y.L., K.X., T.-Y.L., L.C., H.-Y.W., C.-X.L., D.-Y.Z.), Nanjing Medical University, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ting-You","family":"Li","sequence":"additional","affiliation":[{"name":"From the Institution of Stem Cells and Neuroregeneration (H.-Y.N., Y.-X.S., Y.-H.L., B.C., D.-L.W., Y.Z., J.D., H.-Y.L., K.X., T.-Y.L., L.C., H.-Y.W., C.-X.L., D.-Y.Z.), Nanjing Medical University, China"},{"name":"Department of Pharmacology, School of Pharmacy (H.-Y.N., Y.-X.S., Y.-H.L., B.C., D.-L.W., Y.Z., J.D., H.-Y.L., K.X., T.-Y.L., L.C., H.-Y.W., C.-X.L., D.-Y.Z.), Nanjing Medical University, China"},{"name":"Department of Medicinal Chemistry, School of Pharmacy (T.-Y.L.), Nanjing Medical University, China"},{"name":"Collaborative Innovation Center for Cardiovascular Disease Translational Medicine, Nanjing, China (T.-Y.L., C.-X.L., D.-Y.Z.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Chang","sequence":"additional","affiliation":[{"name":"From the Institution of Stem Cells and Neuroregeneration (H.-Y.N., Y.-X.S., Y.-H.L., B.C., D.-L.W., Y.Z., J.D., H.-Y.L., K.X., T.-Y.L., L.C., H.-Y.W., C.-X.L., D.-Y.Z.), Nanjing Medical University, China"},{"name":"Department of Pharmacology, School of Pharmacy (H.-Y.N., Y.-X.S., Y.-H.L., B.C., D.-L.W., Y.Z., J.D., H.-Y.L., K.X., T.-Y.L., L.C., H.-Y.W., C.-X.L., D.-Y.Z.), Nanjing Medical University, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hai-Yin","family":"Wu","sequence":"additional","affiliation":[{"name":"From the Institution of Stem Cells and Neuroregeneration (H.-Y.N., Y.-X.S., Y.-H.L., B.C., D.-L.W., Y.Z., J.D., H.-Y.L., K.X., T.-Y.L., L.C., H.-Y.W., C.-X.L., D.-Y.Z.), Nanjing Medical University, China"},{"name":"Department of Pharmacology, School of Pharmacy (H.-Y.N., Y.-X.S., Y.-H.L., B.C., D.-L.W., Y.Z., J.D., H.-Y.L., K.X., T.-Y.L., L.C., H.-Y.W., C.-X.L., D.-Y.Z.), Nanjing Medical University, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chun-Xia","family":"Luo","sequence":"additional","affiliation":[{"name":"From the Institution of Stem Cells and Neuroregeneration (H.-Y.N., Y.-X.S., Y.-H.L., B.C., D.-L.W., Y.Z., J.D., H.-Y.L., K.X., T.-Y.L., L.C., H.-Y.W., C.-X.L., D.-Y.Z.), Nanjing Medical University, China"},{"name":"Department of Pharmacology, School of Pharmacy (H.-Y.N., Y.-X.S., Y.-H.L., B.C., D.-L.W., Y.Z., J.D., H.-Y.L., K.X., T.-Y.L., L.C., H.-Y.W., C.-X.L., D.-Y.Z.), Nanjing Medical University, China"},{"name":"Collaborative Innovation Center for Cardiovascular Disease Translational Medicine, Nanjing, China (T.-Y.L., C.-X.L., D.-Y.Z.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dong-Ya","family":"Zhu","sequence":"additional","affiliation":[{"name":"From the Institution of Stem Cells and Neuroregeneration (H.-Y.N., Y.-X.S., Y.-H.L., B.C., D.-L.W., Y.Z., J.D., H.-Y.L., K.X., T.-Y.L., L.C., H.-Y.W., C.-X.L., D.-Y.Z.), Nanjing Medical University, China"},{"name":"Department of Pharmacology, School of Pharmacy (H.-Y.N., Y.-X.S., Y.-H.L., B.C., D.-L.W., Y.Z., J.D., H.-Y.L., K.X., T.-Y.L., L.C., H.-Y.W., C.-X.L., D.-Y.Z.), Nanjing Medical University, China"},{"name":"Collaborative Innovation Center for Cardiovascular Disease Translational Medicine, Nanjing, China (T.-Y.L., C.-X.L., D.-Y.Z.)."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.115.008097"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.110.974675"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2014.7692"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1002\/ana.24653"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm.2245"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.4578-12.2013"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.STR.0000231875.96714.b1"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1097\/WCO.0000000000000256"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.107.499962"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1038\/nn.4146"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrn2735"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(11)60325-5"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm.3644"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1101\/lm.1329209"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1012676108"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1305-14.2014"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2006.07.011"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainres.2016.03.045"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1161\/JAHA.117.007236"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0341-17.2017"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature09511"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1002\/jnr.21762"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0896-6273(00)80439-0"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1038\/nn.2634"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1118803109"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.3029-13.2013"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-017-1667-0"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.1177\/1073858407309545"},{"key":"e_1_3_3_30_2","doi-asserted-by":"publisher","DOI":"10.1007\/s11596-014-1242-z"},{"key":"e_1_3_3_31_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1404109111"},{"key":"e_1_3_3_32_2","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awh369"},{"key":"e_1_3_3_33_2","doi-asserted-by":"publisher","DOI":"10.3389\/fncel.2017.00076"},{"key":"e_1_3_3_34_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.4253-06.2006"},{"key":"e_1_3_3_35_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.181213498"},{"key":"e_1_3_3_36_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1215501110"},{"key":"e_1_3_3_37_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jstrokecerebrovasdis.2016.03.004"}],"container-title":["Stroke"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ahajournals.org\/doi\/full\/10.1161\/STROKEAHA.118.022647","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,5,13]],"date-time":"2024-05-13T15:15:20Z","timestamp":1715613320000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ahajournals.org\/doi\/10.1161\/STROKEAHA.118.022647"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,3]]},"references-count":36,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2019,3]]}},"alternative-id":["10.1161\/STROKEAHA.118.022647"],"URL":"https:\/\/doi.org\/10.1161\/strokeaha.118.022647","relation":{},"ISSN":["0039-2499","1524-4628"],"issn-type":[{"value":"0039-2499","type":"print"},{"value":"1524-4628","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,3]]},"assertion":[{"value":"2018-02-12","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-01-02","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-02-07","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}