{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,25]],"date-time":"2026-02-25T12:26:28Z","timestamp":1772022388421,"version":"3.50.1"},"reference-count":38,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"6","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Stroke"],"published-print":{"date-parts":[[2000,6]]},"abstract":"<jats:p>\n            <jats:italic>Background and Purpose<\/jats:italic>\n            \u2014Many patients with acute stroke are excluded from receiving thrombolysis agents within the necessary time limit (3 or 6 hours from stroke onset) because they or their family members are unable provide the time of stroke onset. Brain tissue sodium concentration ([Na\n            <jats:sup>+<\/jats:sup>\n            ]) increases gradually and incessantly during the initial hours of experimental focal cerebral ischemia but only in severely damaged brain regions. We propose that this steady increase in [Na\n            <jats:sup>+<\/jats:sup>\n            ] can be used to estimate the time after arterial occlusion in the rat middle cerebral artery occlusion model of ischemic stroke.\n          <\/jats:p>\n          <jats:p>\n            <jats:italic>Methods<\/jats:italic>\n            \u2014Sixteen anesthetized Sprague-Dawley rats underwent permanent middle cerebral artery occlusion combined with bilateral common artery occlusion. After 100 to 450 minutes, diffusion-weighted MRI was used to generate apparent diffusion coefficient (ADC) maps, cerebral blood flow (CBF) was determined with\n            <jats:sup>14<\/jats:sup>\n            C-iodoantipyrine (in a subset of 7 animals), and the brain was frozen. Autoradiographic CBF sections and punch samples for Na\n            <jats:sup>+<\/jats:sup>\n            analysis were obtained from the brain at the same level of the MR image. Severely at risk regions were identified with an ADC of &lt;520 \u03bcm\n            <jats:sup>2<\/jats:sup>\n            \/s and, in the subset, with both ADC of &lt;520 \u03bcm\n            <jats:sup>2<\/jats:sup>\n            \/s and CBF of &lt;40 mL \u00b7 100 g\n            <jats:sup>\u22121<\/jats:sup>\n            \u00b7 min\n            <jats:sup>\u22121<\/jats:sup>\n            .\n          <\/jats:p>\n          <jats:p>\n            <jats:italic>Results<\/jats:italic>\n            \u2014Both CBF and the ADC dropped quickly and remained stable in the initial hours after ischemic onset. Linear regression revealed strong linearity between [Na\n            <jats:sup>+<\/jats:sup>\n            ] and time after onset, with a slope of 0.95 or 1.00 (mEq\/kg DW)\/min, with both ADC and ADC-plus-CBF criteria, respectively. The 95% CIs at 180 and 360 minutes were between 41 and 52 minutes.\n          <\/jats:p>\n          <jats:p>\n            <jats:italic>Conclusions<\/jats:italic>\n            \u2014The time after ischemic onset can be estimated with this 2-step process. First, ADC and CBF are used to identify severely endangered regions. Second, the [Na\n            <jats:sup>+<\/jats:sup>\n            ] in these regions is used to estimate time after onset. The favorable 95% CIs at the time limits for thrombolytic therapy and the availability of measurements of ADC, CBF, and [Na\n            <jats:sup>+<\/jats:sup>\n            ] in humans through the use of MRI suggest that this time-estimation scheme could be used to assess the appropriateness of thrombolysis for patients who do not know when the stroke occurred.\n          <\/jats:p>","DOI":"10.1161\/01.str.31.6.1386","type":"journal-article","created":{"date-parts":[[2011,6,17]],"date-time":"2011-06-17T20:08:03Z","timestamp":1308341283000},"page":"1386-1392","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":54,"title":["Brain Tissue Sodium Is a Ticking Clock Telling Time After Arterial Occlusion in Rat Focal Cerebral Ischemia"],"prefix":"10.1161","volume":"31","author":[{"given":"Yang","family":"Wang","sequence":"first","affiliation":[{"name":"From the Department of Anesthesiology (S.C.J.), Allegheny General Hospital, Pittsburgh, Pa; and the Cleveland Clinic Foundation (Y.W., W.H., A.D.P.-T., T.C.N., A.J.F., A.W.M.), Cleveland, Ohio."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Weixing","family":"Hu","sequence":"additional","affiliation":[{"name":"From the Department of Anesthesiology (S.C.J.), Allegheny General Hospital, Pittsburgh, Pa; and the Cleveland Clinic Foundation (Y.W., W.H., A.D.P.-T., T.C.N., A.J.F., A.W.M.), Cleveland, Ohio."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alejandro D.","family":"Perez-Trepichio","sequence":"additional","affiliation":[{"name":"From the Department of Anesthesiology (S.C.J.), Allegheny General Hospital, Pittsburgh, Pa; and the Cleveland Clinic Foundation (Y.W., W.H., A.D.P.-T., T.C.N., A.J.F., A.W.M.), Cleveland, Ohio."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thian C.","family":"Ng","sequence":"additional","affiliation":[{"name":"From the Department of Anesthesiology (S.C.J.), Allegheny General Hospital, Pittsburgh, Pa; and the Cleveland Clinic Foundation (Y.W., W.H., A.D.P.-T., T.C.N., A.J.F., A.W.M.), Cleveland, Ohio."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anthony J.","family":"Furlan","sequence":"additional","affiliation":[{"name":"From the Department of Anesthesiology (S.C.J.), Allegheny General Hospital, Pittsburgh, Pa; and the Cleveland Clinic Foundation (Y.W., W.H., A.D.P.-T., T.C.N., A.J.F., A.W.M.), Cleveland, Ohio."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anthony W.","family":"Majors","sequence":"additional","affiliation":[{"name":"From the Department of Anesthesiology (S.C.J.), Allegheny General Hospital, Pittsburgh, Pa; and the Cleveland Clinic Foundation (Y.W., W.H., A.D.P.-T., T.C.N., A.J.F., A.W.M.), Cleveland, Ohio."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stephen C.","family":"Jones","sequence":"additional","affiliation":[{"name":"From the Department of Anesthesiology (S.C.J.), Allegheny General Hospital, Pittsburgh, Pa; and the Cleveland Clinic Foundation (Y.W., W.H., A.D.P.-T., T.C.N., A.J.F., A.W.M.), Cleveland, Ohio."}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"276","reference":[{"key":"e_1_3_2_1_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199512143332401"},{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.282.21.2003"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1161\/str.29.1.4"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.282.21.2019"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1161\/str.30.1.40"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1161\/str.27.3.398"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1001\/archinte.1993.00410220058006"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1161\/str.11.6.7210064"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1148\/radiology.213.1.r99se15156"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1161\/str.26.4.667"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1161\/str.17.4.2943059"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1148\/radiology.161.2.3763909"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1152\/jappl.1969.27.2.296"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.1978.234.1.H59"},{"key":"e_1_3_2_15_2","unstructured":"Hu W Kharlamov A Wang Y Perez-Trepichio AD Jones SC. 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