{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,21]],"date-time":"2026-02-21T05:09:40Z","timestamp":1771650580617,"version":"3.50.1"},"reference-count":22,"publisher":"S. Karger AG","issue":"1","license":[{"start":{"date-parts":[[2017,10,13]],"date-time":"2017-10-13T00:00:00Z","timestamp":1507852800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.karger.com\/Services\/SiteLicenses"},{"start":{"date-parts":[[2017,10,13]],"date-time":"2017-10-13T00:00:00Z","timestamp":1507852800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.karger.com\/Services\/SiteLicenses"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Neonatology"],"published-print":{"date-parts":[[2018]]},"abstract":"<b><i>Background:<\/i><\/b> Hypoxia-ischemia (HI) results in increased activation of Ca<sup>2+<\/sup>\/calmodulin kinase IV (CaM kinase IV) mediated by Src kinase. Therapeutic hypothermia ameliorates neuronal injury in the newborn. <b><i>Hypothesis:<\/i><\/b> Inhibition of Src kinase concurrently with hypothermia further attenuates the hypoxia-induced increased activation of CaM kinase IV compared with hypothermia alone. <b><i>Design\/Methods:<\/i><\/b> Ventilated piglets were exposed to HI, received saline or a selective Src kinase inhibitor (PP2), and were cooled to 33\u00b0C. Neuropathology, adenosine triphosphate (ATP) and phosphocreatine (PCr) concentrations, and CaM kinase IV activity were determined. <b><i>Results:<\/i><\/b> The neuropathology mean score (mean \u00b1 SD) was 0.4 \u00b1 0.43 in normoxia-normothermia (<i>p<\/i> < 0.05 vs. hypoxia-normothermia), 3.5 \u00b1 0.89 in hypoxia-normothermia (<i>p<\/i> < 0.05 vs. normoxia-normothermia), 0.7 \u00b1 0.73 in hypoxia-hypothermia (<i>p<\/i> < 0.05 vs. normoxia-normothermia), and 0.5 \u00b1 0.70 in normoxia-hypothermia (<i>p<\/i> < 0.05 vs. hypoxia-normothermia). The CaM kinase IV activity in cerebral tissue (pmol Pi\/mg protein\/min; mean \u00b1 SD) was 2,002 \u00b1 729 in normoxia-normothermia, 1,704 \u00b1 18 in normoxia-hypothermia, 6,017 \u00b1 2,510 in hypoxia-normothermia, 4,104 \u00b1 542 in hypoxia-hypothermia (<i>p<\/i> < 0.05 vs. normoxia-hypothermia), and 2,165 \u00b1 415 in hypoxia-hypothermia with PP2 (<i>p<\/i> < 0.05 vs. hypoxia-hypothermia). The hypoxic groups with and without hypothermia or Src kinase inhibitor were comparable in the levels of ATP and PCr, indicating that they were similar in their degree of energy failure prior to treatments. Hypothermia or Src kinase inhibitor (PP2) did not restore the ATP and PCr levels. <b><i>Conclusions:<\/i><\/b> Hypothermia and Src kinase inhibition attenuated apoptotic cell death and improved neuropathology after hypoxia. The combination of short-duration hypothermia with Src kinase inhibition following hypoxia further attenuates the increased activation of CaM kinase IV compared to hypothermia alone in the newborn swine brain.<\/jats:p>","DOI":"10.1159\/000480067","type":"journal-article","created":{"date-parts":[[2017,10,12]],"date-time":"2017-10-12T21:01:53Z","timestamp":1507842113000},"page":"37-43","source":"Crossref","is-referenced-by-count":14,"title":["Effect of Concurrent Src Kinase Inhibition with Short-Duration Hypothermia on Ca<sup>2+<\/sup>\/Calmodulin Kinase IV Activity and Neuropathology after Hypoxia-Ischemia in the Newborn Swine Brain"],"prefix":"10.1159","volume":"113","author":[{"given":"Panagiotis","family":"Kratimenos","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ioannis","family":"Koutroulis","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amit","family":"Jain","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shadi","family":"Malaeb","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria","family":"Delivoria-Papadopoulos","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"127","published-online":{"date-parts":[[2017,10,13]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(05)71048-5"},{"key":"ref2","doi-asserted-by":"publisher","DOI":"10.1136\/adc.2008.148205"},{"key":"ref3","doi-asserted-by":"publisher","DOI":"10.1016\/j.clp.2009.07.011"},{"key":"ref4","doi-asserted-by":"publisher","DOI":"10.1038\/pr.2016.198"},{"key":"ref5","doi-asserted-by":"publisher","DOI":"10.1016\/j.neulet.2011.01.017"},{"key":"ref6","doi-asserted-by":"publisher","DOI":"10.1007\/s11064-007-9574-8"},{"key":"ref7","doi-asserted-by":"publisher","DOI":"10.1002\/14651858.CD003311.pub3"},{"key":"ref8","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1112066"},{"key":"ref9","doi-asserted-by":"publisher","DOI":"10.1007\/s11064-015-1717-8"},{"key":"ref10","doi-asserted-by":"publisher","DOI":"10.1007\/s11064-014-1404-1"},{"key":"ref11","doi-asserted-by":"publisher","DOI":"10.1007\/s11064-011-0477-3"},{"key":"ref12","doi-asserted-by":"publisher","DOI":"10.1016\/j.neulet.2008.05.095"},{"key":"ref13","doi-asserted-by":"publisher","DOI":"10.1016\/j.jneumeth.2014.04.005"},{"key":"ref14","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.1975.tb03859.x"},{"key":"ref15","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.270.51.30464"},{"key":"ref16","doi-asserted-by":"publisher","DOI":"10.1016\/S0968-0004(99)01383-3"},{"key":"ref17","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.00152.2005"},{"key":"ref18","doi-asserted-by":"publisher","DOI":"10.1089\/neu.2007.0482"},{"key":"ref19","doi-asserted-by":"publisher","DOI":"10.1016\/j.pediatrneurol.2010.05.009"},{"key":"ref20","doi-asserted-by":"publisher","DOI":"10.1517\/14728222.2014.952280"},{"key":"ref21","doi-asserted-by":"publisher","DOI":"10.1203\/00006450-199611000-00014"},{"key":"ref22","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijbiomac.2016.12.024"}],"container-title":["Neonatology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.karger.com\/Article\/Pdf\/480067","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.karger.com\/Article\/Pdf\/480067","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,4,23]],"date-time":"2025-04-23T16:51:41Z","timestamp":1745427101000},"score":1,"resource":{"primary":{"URL":"https:\/\/karger.com\/article\/doi\/10.1159\/000480067"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,10,13]]},"references-count":22,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2017,12,13]]}},"URL":"https:\/\/doi.org\/10.1159\/000480067","archive":["Portico"],"relation":{},"ISSN":["1661-7800","1661-7819"],"issn-type":[{"value":"1661-7800","type":"print"},{"value":"1661-7819","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,10,13]]}}}