{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,5]],"date-time":"2026-01-05T22:31:45Z","timestamp":1767652305365},"reference-count":44,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"2","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Stroke"],"published-print":{"date-parts":[[2002,2]]},"abstract":"<jats:p>\n            <jats:bold>\n              <jats:italic>\n                <jats:bold>\n                  <jats:italic>Background and Purpose<\/jats:italic>\n                <\/jats:bold>\n                \u2014\n              <\/jats:italic>\n            <\/jats:bold>\n            Phosphatidylinositol 3\u2013kinase (PI3-kinase) is involved in smooth muscle contraction induced by growth factors and\/or G protein\u2013coupled receptor agonists. To evaluate the role of PI3-kinase in the pathogenesis of delayed vasospasm, we applied 2 PI3-kinase inhibitors to an established canine double-hemorrhage model of experimental subarachnoid hemorrhage.\n          <\/jats:p>\n          <jats:p>\n            <jats:bold>\n              <jats:italic>\n                <jats:bold>\n                  <jats:italic>Methods<\/jats:italic>\n                <\/jats:bold>\n                \u2014\n              <\/jats:italic>\n            <\/jats:bold>\n            Twenty-four dogs underwent double blood injections via the cisterna magna on days 0 and 2. The dogs were killed on day 7. Dogs were treated with either vehicle (dimethyl sulfoxide), wortmannin, or LY294002 once per day on day 2 through day 6. Angiography was performed before blood injection and before the dogs were killed. The basilar arteries were collected for morphology, Western blot analysis, and PI3-kinase activity.\n          <\/jats:p>\n          <jats:p>\n            <jats:bold>\n              <jats:italic>\n                <jats:bold>\n                  <jats:italic>Results<\/jats:italic>\n                <\/jats:bold>\n                \u2014\n              <\/jats:italic>\n            <\/jats:bold>\n            The residual diameter of the basilar arteries in the dimethyl sulfoxide treatment group, which was compared with day 0 angiogram, decreased markedly on day 7 (the percentage of the residual diameter was 47.8\u00b10.8%). Wortmannin and LY294002 did not significantly change residual diameter on day 7. Both PI3-kinase inhibitors abolished PI3-kinase activity compared with the vehicle treatment group. However, both PI3-kinase inhibitors failed to significantly attenuate PI3-kinase protein expression (Western blot) (\n            <jats:italic>P<\/jats:italic>\n            &gt;0.05, ANOVA).\n          <\/jats:p>\n          <jats:p>\n            <jats:bold>\n              <jats:italic>\n                <jats:bold>\n                  <jats:italic>Conclusions<\/jats:italic>\n                <\/jats:bold>\n                \u2014\n              <\/jats:italic>\n            <\/jats:bold>\n            Delayed treatment, which was to mimic the clinical situation, with PI3-kinase inhibitors failed to reverse vasospasm. PI3-kinase may not play an important role in the delayed vasospasm. The possible effect of PI3-kinase inhibitors in the early stage of vasospasm was not investigated in the present study.\n          <\/jats:p>","DOI":"10.1161\/hs0202.103398","type":"journal-article","created":{"date-parts":[[2002,7,28]],"date-time":"2002-07-28T23:16:47Z","timestamp":1027898207000},"page":"593-599","update-policy":"http:\/\/dx.doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":7,"title":["Phosphatidylinositol 3\u2013Kinase Inhibitor Failed to Reduce Cerebral Vasospasm in Dog Model of Experimental Subarachnoid Hemorrhage"],"prefix":"10.1161","volume":"33","author":[{"given":"Hitoshi","family":"Kimura","sequence":"first","affiliation":[{"name":"From the Departments of Neurosurgery (H.K., T.M., J.H.Z.) and Pharmacology and Toxicology (K.S.), University of Mississippi Medical Center, Jackson."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kenroh","family":"Sasaki","sequence":"additional","affiliation":[{"name":"From the Departments of Neurosurgery (H.K., T.M., J.H.Z.) and Pharmacology and Toxicology (K.S.), University of Mississippi Medical Center, Jackson."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Toshinari","family":"Meguro","sequence":"additional","affiliation":[{"name":"From the Departments of Neurosurgery (H.K., T.M., J.H.Z.) and Pharmacology and Toxicology (K.S.), University of Mississippi Medical Center, Jackson."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John H.","family":"Zhang","sequence":"additional","affiliation":[{"name":"From the Departments of Neurosurgery (H.K., T.M., J.H.Z.) and Pharmacology and Toxicology (K.S.), University of Mississippi Medical Center, Jackson."}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"276","reference":[{"key":"e_1_3_2_1_2","doi-asserted-by":"publisher","DOI":"10.1161\/str.29.2.351"},{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1161\/str.28.3.660"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1042-3680(18)30256-0"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-0185(199804)253:2<58::AID-AR9>3.0.CO;2-A"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0090-3019(98)00133-5"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1080\/02688699550041386"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1097\/00006123-200003000-00001"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1227\/00006123-198606000-00026"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.274.13.8347"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0968-0004(97)01061-X"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1124\/mol.54.6.1007"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1161\/str.31.2.526"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1161\/str.31.6.1377"},{"key":"e_1_3_2_14_2","first-page":"1179","volume":"291","year":"1999","unstructured":"Banes A, Florian JA, Watts S. 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