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According to clinical studies, magnesium sulphate (MgSO\n                      <jats:sub>4<\/jats:sub>\n                      ) given to women in preterm labor reduces the risk of cerebral palsy in the offspring but the mechanisms behind its neuroprotective effects are still unclear. Our aim was to explore whether MgSO\n                      <jats:sub>4<\/jats:sub>\n                      induces tolerance (preconditioning) in the preterm rodent brain. For this purpose we established a model of perinatal hypoxia\u2010ischemia (HI) in postnatal day 4 rats and also applied a recently developed postnatal day 5 mouse model of perinatal brain injury.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Postnatal day 4 Wistar rats were exposed to unilateral carotid artery ligation followed by 60, 70 or 80\u202fmin of hypoxia (8% O\n                      <jats:sub>2<\/jats:sub>\n                      ). On postnatal day 11, brains were collected and macroscopically visible damage as well as white and grey matter injury was examined using immunohistochemical staining. Once the model had been established, a possible preconditioning protection induced by a bolus MgSO\n                      <jats:sub>4<\/jats:sub>\n                      injection prior to 80\u202fmin HI was examined 7\u202fdays after the insult. Next, a MgSO\n                      <jats:sub>4<\/jats:sub>\n                      bolus was injected in C57Bl6 mice on PND 4 followed by exposure to unilateral carotid artery ligation and hypoxia, (10% O\n                      <jats:sub>2<\/jats:sub>\n                      ) for 70\u202fmin on PND 5. Brains were collected 7\u202fdays after the insult and examined with immunohistochemistry for grey and white matter injury.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>In rats, a 60\u202fmin period of hypoxia resulted in very few animals with brain injury and although 70\u202fmin of hypoxia resulted in a higher percentage of injured animals, the brains were marginally damaged. An 80\u202fmin exposure of hypoxia caused cortical tissue damage combined with hippocampal atrophy and neuronal loss in the C3 hippocampal layer.<\/jats:p>\n                    <jats:p>\n                      In the rat model, MgSO\n                      <jats:sub>4<\/jats:sub>\n                      (1.1\u202fmg\/g administered\n                      <jats:italic>i.p.<\/jats:italic>\n                      24\u202fh prior to the induction of HI, resulting in a transient serum Mg\n                      <jats:sup>2+<\/jats:sup>\n                      concentration elevation to 4.1\u202f\u00b1\u202f0.2\u202fmmol\/l at 3\u202fh post\n                      <jats:italic>i.p.<\/jats:italic>\n                      injection) reduced brain injury by 74% in grey matter and 64% in white matter.\n                    <\/jats:p>\n                    <jats:p>\n                      In the mouse model, MgSO\n                      <jats:sub>4<\/jats:sub>\n                      (0.92\u202fmg\/g)\n                      <jats:italic>i.p.<\/jats:italic>\n                      injection given 24\u202fh prior to the HI insult resulted in a Mg\n                      <jats:sup>2+<\/jats:sup>\n                      serum concentration increase reaching 2.7\u202f\u00b1\u202f0.3\u202fmmol\/l at 3\u202fh post injection, which conferred a 40% reduction in grey matter injury.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      We have established a postnatal day 4 rat model of HI for the study of preterm brain injury. MgSO\n                      <jats:sub>4<\/jats:sub>\n                      provides a marked preconditioning protection both in postnatal day 4 rats and in postnatal day 5 mice.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1016\/j.ijdevneu.2018.01.002","type":"journal-article","created":{"date-parts":[[2018,2,2]],"date-time":"2018-02-02T22:28:46Z","timestamp":1517610526000},"page":"56-66","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Magnesium sulphate induces preconditioning in preterm rodent models of cerebral hypoxia\u2010ischemia"],"prefix":"10.1002","volume":"70","author":[{"given":"Gabriella","family":"Koning","sequence":"first","affiliation":[{"name":"Perinatal Center, Institutes of Neuroscience and Physiology &amp; Clinical Sciences Sahlgrenska Academy Gothenburg University Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ellinor","family":"Lyngfelt","sequence":"additional","affiliation":[{"name":"Perinatal Center, Institutes of Neuroscience and Physiology &amp; 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