{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T05:34:02Z","timestamp":1789450442117,"version":"build-2803163510"},"reference-count":58,"publisher":"SAGE Publications","issue":"5","license":[{"start":{"date-parts":[[2024,12,4]],"date-time":"2024-12-04T00:00:00Z","timestamp":1733270400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["J Cereb Blood Flow Metab"],"published-print":{"date-parts":[[2025,5]]},"abstract":"\n Familial hemiplegic migraine type 2 (FHM2) is linked to Na,K-ATPase \u03b1\n 2<\/jats:sub>\n isoform mutations, including that of G301R. Mice heterozygous for this mutation (\n \n \n \n \n \n \u03b1<\/mml:mo>\n <\/mml:mrow>\n 2<\/mml:mn>\n \n +<\/mml:mo>\n \/<\/mml:mo>\n G3<\/mml:mtext>\n 0<\/mml:mn>\n 1R<\/mml:mtext>\n <\/mml:mrow>\n <\/mml:msubsup>\n <\/mml:mrow>\n <\/mml:math>\n <\/jats:inline-formula>\n ) show cerebrovascular hypercontractility associated with amplified Src kinase signaling, and exaggerated neurovascular coupling. This study hypothesized that targeting Na,K-ATPase-dependent Src phosphorylation with pNaKtide would normalize cerebral perfusion and neurovascular coupling in\n \n \n \n \n \n \u03b1<\/mml:mo>\n <\/mml:mrow>\n 2<\/mml:mn>\n \n +<\/mml:mo>\n \/<\/mml:mo>\n G3<\/mml:mtext>\n 0<\/mml:mn>\n 1R<\/mml:mtext>\n <\/mml:mrow>\n <\/mml:msubsup>\n <\/mml:mrow>\n <\/mml:math>\n <\/jats:inline-formula>\n mice. The effect of pNaKtide on cerebral blood flow and neurovascular coupling was assessed using laser speckle contrast imaging in awake, head-fixed mice with cranial windows in a longitudinal study design. At baseline, compared to wild type,\n \n \n \n \n \n \u03b1<\/mml:mo>\n <\/mml:mrow>\n 2<\/mml:mn>\n \n +<\/mml:mo>\n \/<\/mml:mo>\n G3<\/mml:mtext>\n 0<\/mml:mn>\n 1R<\/mml:mtext>\n <\/mml:mrow>\n <\/mml:msubsup>\n <\/mml:mrow>\n <\/mml:math>\n <\/jats:inline-formula>\n mice exhibited increased middle cerebral artery tone; with whisker stimulation leading to an exaggerated increase in sensory cortex blood flow. No difference between genotypes in telemetrically assessed blood pressure occurred. The exaggerated neurovascular coupling in\n \n \n \n \n \n \u03b1<\/mml:mo>\n <\/mml:mrow>\n 2<\/mml:mn>\n \n +<\/mml:mo>\n \/<\/mml:mo>\n G3<\/mml:mtext>\n 0<\/mml:mn>\n 1R<\/mml:mtext>\n <\/mml:mrow>\n <\/mml:msubsup>\n <\/mml:mrow>\n <\/mml:math>\n <\/jats:inline-formula>\n mice was associated with increased K\n ir<\/jats:sub>\n 2.1 channel expression in cerebrovascular endothelium. Two weeks pNaKtide treatment normalized cerebral artery tone, endothelial K\n ir<\/jats:sub>\n 2.1 expression, and neurovascular coupling in\n \n \n \n \n \n \u03b1<\/mml:mo>\n <\/mml:mrow>\n 2<\/mml:mn>\n \n +<\/mml:mo>\n \/<\/mml:mo>\n G3<\/mml:mtext>\n 0<\/mml:mn>\n 1R<\/mml:mtext>\n <\/mml:mrow>\n <\/mml:msubsup>\n <\/mml:mrow>\n <\/mml:math>\n <\/jats:inline-formula>\n mice. Inhibition of the Na,K-ATPase-dependent Src kinase signaling with pNaKtide prevented excessive vasoconstriction and disturbances in neurovascular coupling in\n \n \n \n \n \n \u03b1<\/mml:mo>\n <\/mml:mrow>\n 2<\/mml:mn>\n \n +<\/mml:mo>\n \/<\/mml:mo>\n G3<\/mml:mtext>\n 0<\/mml:mn>\n 1R<\/mml:mtext>\n <\/mml:mrow>\n <\/mml:msubsup>\n <\/mml:mrow>\n <\/mml:math>\n <\/jats:inline-formula>\n mice. pNaKtide had only minor hypotensive effect similar in both genotypes. These results demonstrate a novel treatment target to normalize cerebral perfusion in FHM2.\n <\/jats:p>","DOI":"10.1177\/0271678x241305562","type":"journal-article","created":{"date-parts":[[2024,12,4]],"date-time":"2024-12-04T03:32:36Z","timestamp":1733283156000},"page":"842-854","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":8,"title":["Targeting Na,K-ATPase-Src signaling to normalize cerebral blood flow in a murine model of familial hemiplegic migraine"],"prefix":"10.1177","volume":"45","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5431-4409","authenticated-orcid":false,"given":"Christian","family":"Staehr","sequence":"first","affiliation":[{"name":"Department of Biomedicine, Aarhus University, Aarhus, Denmark"},{"name":"Department of Anesthesiology and Intensive Care, Aarhus University Hospital, Aarhus, Denmark"},{"name":"School of Clinical Medicine, University of Queensland, St Lucia, Qld, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Halvor \u00d8sterby","family":"Guldbrandsen","sequence":"additional","affiliation":[{"name":"Department of Biomedicine, Aarhus University, Aarhus, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Casper","family":"Homilius","sequence":"additional","affiliation":[{"name":"Department of Biomedicine, Aarhus University, Aarhus, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura \u00d8llegaard","family":"Johnsen","sequence":"additional","affiliation":[{"name":"Department of Biomedicine, Aarhus University, Aarhus, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dmitry","family":"Postnov","sequence":"additional","affiliation":[{"name":"Center of Functionally Integrative Neuroscience, Aarhus University, Aarhus, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7950-4647","authenticated-orcid":false,"given":"Tina M","family":"Pedersen","sequence":"additional","affiliation":[{"name":"Department of Biomedicine, Aarhus University, Aarhus, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandrine","family":"Pierre","sequence":"additional","affiliation":[{"name":"Institute for Interdisciplinary Research, Marshall University, Huntington, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shaun L","family":"Sandow","sequence":"additional","affiliation":[{"name":"School of Clinical Medicine, University of Queensland, St Lucia, Qld, Australia"},{"name":"School of Health, University of the Sunshine Coast, Maroochydore, Qld, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3303-1095","authenticated-orcid":false,"given":"Vladimir V","family":"Matchkov","sequence":"additional","affiliation":[{"name":"Department of Biomedicine, Aarhus University, Aarhus, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2024,12,4]]},"reference":[{"key":"e_1_3_7_2_2","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2016.00161"},{"key":"e_1_3_7_3_2","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2016.00239"},{"key":"e_1_3_7_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng1081"},{"key":"e_1_3_7_5_2","doi-asserted-by":"publisher","DOI":"10.1002\/glia.22629"},{"key":"e_1_3_7_6_2","doi-asserted-by":"publisher","DOI":"10.1007\/s11064-022-03849-w"},{"key":"e_1_3_7_7_2","doi-asserted-by":"publisher","DOI":"10.1093\/cercor\/12.5.515"},{"key":"e_1_3_7_8_2","doi-asserted-by":"publisher","DOI":"10.1113\/EP087519"},{"key":"e_1_3_7_9_2","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2016.00179"},{"key":"e_1_3_7_10_2","doi-asserted-by":"publisher","DOI":"10.1042\/CS20220796"},{"key":"e_1_3_7_11_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10048-004-0183-2"},{"key":"e_1_3_7_12_2","doi-asserted-by":"publisher","DOI":"10.1038\/srep22047"},{"key":"e_1_3_7_13_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1002129"},{"key":"e_1_3_7_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2020.11.018"},{"key":"e_1_3_7_15_2","doi-asserted-by":"publisher","DOI":"10.15252\/emmm.201505944"},{"key":"e_1_3_7_16_2","doi-asserted-by":"publisher","DOI":"10.1002\/glia.23194"},{"key":"e_1_3_7_17_2","doi-asserted-by":"publisher","DOI":"10.3389\/fneur.2018.00019"},{"key":"e_1_3_7_18_2","doi-asserted-by":"publisher","DOI":"10.1186\/s10194-021-01353-0"},{"key":"e_1_3_7_19_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-018-35285-8"},{"key":"e_1_3_7_20_2","doi-asserted-by":"publisher","DOI":"10.1177\/0271678X18761712"},{"key":"e_1_3_7_21_2","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/cvz306"},{"key":"e_1_3_7_22_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1468-2982.2004.00740.x"},{"key":"e_1_3_7_23_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF00867591"},{"key":"e_1_3_7_24_2","doi-asserted-by":"publisher","DOI":"10.1038\/nn.4533"},{"key":"e_1_3_7_25_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1800201115"},{"key":"e_1_3_7_26_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2025998118"},{"key":"e_1_3_7_27_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1401811111"},{"key":"e_1_3_7_28_2","doi-asserted-by":"publisher","DOI":"10.1111\/micc.12190"},{"key":"e_1_3_7_29_2","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.119.312493"},{"key":"e_1_3_7_30_2","doi-asserted-by":"publisher","DOI":"10.1038\/srep34592"},{"key":"e_1_3_7_31_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.00347.2016"},{"key":"e_1_3_7_32_2","doi-asserted-by":"publisher","DOI":"10.1111\/apha.13652"},{"key":"e_1_3_7_33_2","doi-asserted-by":"publisher","DOI":"10.1111\/apha.13059"},{"key":"e_1_3_7_34_2","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2022.1007340"},{"key":"e_1_3_7_35_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M109.013821"},{"key":"e_1_3_7_36_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-019-39137-x"},{"key":"e_1_3_7_37_2","doi-asserted-by":"publisher","DOI":"10.1364\/BOE.507367"},{"key":"e_1_3_7_38_2","doi-asserted-by":"publisher","DOI":"10.1364\/BOE.426521"},{"key":"e_1_3_7_39_2","doi-asserted-by":"publisher","DOI":"10.1097\/00004647-200103000-00002"},{"key":"e_1_3_7_40_2","doi-asserted-by":"publisher","DOI":"10.1364\/BOE.7.002759"},{"key":"e_1_3_7_41_2","doi-asserted-by":"publisher","DOI":"10.1161\/JAHA.123.029527"},{"key":"e_1_3_7_42_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1468-2982.1996.1603161.x"},{"key":"e_1_3_7_43_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1468-2982.2002.00370.x"},{"key":"e_1_3_7_44_2","doi-asserted-by":"publisher","DOI":"10.3389\/fneur.2022.895476"},{"key":"e_1_3_7_45_2","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.112.193045"},{"key":"e_1_3_7_46_2","volume-title":"Integrated systems physiology: from molecule to function. The cerebral circulation","author":"Cipolla MJ.","year":"2009","unstructured":"Cipolla MJ. Integrated systems physiology: from molecule to function. The cerebral circulation. San Rafael, CA: Morgan & Claypool Life Sciences. Copyright \u00a9 2010 by Morgan & Claypool Life Sciences, 2009."},{"key":"e_1_3_7_47_2","doi-asserted-by":"publisher","DOI":"10.1161\/JAHA.121.021814"},{"key":"e_1_3_7_48_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1468-2982.2008.01542.x"},{"key":"e_1_3_7_49_2","doi-asserted-by":"publisher","DOI":"10.1177\/0333102412474503"},{"key":"e_1_3_7_50_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1468-2982.2003.00609.x"},{"key":"e_1_3_7_51_2","doi-asserted-by":"publisher","DOI":"10.1155\/2015\/574186"},{"key":"e_1_3_7_52_2","doi-asserted-by":"publisher","DOI":"10.1111\/head.12194"},{"key":"e_1_3_7_53_2","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.58.7.1066"},{"key":"e_1_3_7_54_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.00154.2017"},{"key":"e_1_3_7_55_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-022-10195-y"},{"key":"e_1_3_7_56_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2016.11.069"},{"key":"e_1_3_7_57_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2010.03.060"},{"key":"e_1_3_7_58_2","doi-asserted-by":"publisher","DOI":"10.1364\/OL.33.002886"},{"key":"e_1_3_7_59_2","doi-asserted-by":"publisher","DOI":"10.1117\/1.3285504"}],"container-title":["Journal of Cerebral Blood Flow & Metabolism"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/0271678X241305562","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/full-xml\/10.1177\/0271678X241305562","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/0271678X241305562","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,2]],"date-time":"2026-05-02T07:47:18Z","timestamp":1777708038000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.1177\/0271678X241305562"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,12,4]]},"references-count":58,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2025,5]]}},"alternative-id":["10.1177\/0271678X241305562"],"URL":"https:\/\/doi.org\/10.1177\/0271678x241305562","relation":{},"ISSN":["0271-678X","1559-7016"],"issn-type":[{"value":"0271-678X","type":"print"},{"value":"1559-7016","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,12,4]]}}}