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Recently, it was shown that signal responsible for rapid<jats:styled-content style=\"fixed-case\">IT<\/jats:styled-content>induction (tolerance induction factor \u2013<jats:styled-content style=\"fixed-case\">TIF<\/jats:styled-content>) is transmitted via circulating blood. In this study, we have hypothesized about the role of the blood cell compartment in<jats:styled-content style=\"fixed-case\">TIF<\/jats:styled-content>production. We used hind\u2010limb ischemia to generate<jats:styled-content style=\"fixed-case\">TIF<\/jats:styled-content>as a rapid preconditioning against transient middle cerebral artery occlusion (<jats:styled-content style=\"fixed-case\">MCAO<\/jats:styled-content>). The essential properties of protein synthesis inhibitors actinomycin D and cycloheximide were utilized to obtain the following results: (i)<jats:styled-content style=\"fixed-case\">TIF<\/jats:styled-content>is proteinaceous. Hind\u2010limb ischemia mediates gene expression followed by translation, resulting in the production of<jats:styled-content style=\"fixed-case\">TIF<\/jats:styled-content>. Blocking of each of these two steps in protein synthesis resulted in rapid infarct evolution (281.5\u00a0\u00b1\u00a023.37 and 330.4\u00a0\u00b1\u00a071.8\u00a0mm<jats:sup>3<\/jats:sup>, respectively). (ii) Tourniquet\u2010treated muscle is not a source of<jats:styled-content style=\"fixed-case\">TIF<\/jats:styled-content>. Actinomicine D injected into rat prior to tolerance induction significantly suppressed<jats:styled-content style=\"fixed-case\">RNA<\/jats:styled-content>synthesis in blood cells and muscle tissue. Cross\u2010circulation of those rats (donors) with control animals (recipients) did not mediate significant infarct reduction (272.9\u00a0\u00b1\u00a012.45\u00a0mm<jats:sup>3<\/jats:sup>), even when hind\u2010limb ischemia was performed before<jats:styled-content style=\"fixed-case\">MCAO<\/jats:styled-content>in the recipient (223.2\u00a0\u00b1\u00a037.51\u00a0mm<jats:sup>3<\/jats:sup>). (iii) Blood cells serve as a source of<jats:styled-content style=\"fixed-case\">TIF<\/jats:styled-content>. Preischemic transfusion of plasma\u2010free, protein\u2010synthesis\u2010inactive blood cells, which were obtained from tolerant animals did not reduce infarct volume in recipients (131\u00a0\u00b1\u00a016.1\u00a0mm<jats:sup>3<\/jats:sup>) in a range comparable with their protein\u2010synthesis\u2010active counterparts (17.2\u00a0\u00b1\u00a012\u00a0mm<jats:sup>3<\/jats:sup>). We can conclude that blood cells are associated with the induction of rapid<jats:styled-content style=\"fixed-case\">IT<\/jats:styled-content>via production of a bioactive proteinaceous substance.<\/jats:p>","DOI":"10.1111\/ejn.13422","type":"journal-article","created":{"date-parts":[[2016,10,12]],"date-time":"2016-10-12T19:05:37Z","timestamp":1476299137000},"page":"2958-2965","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Blood cells serve as a source of factor\u2010inducing rapid ischemic tolerance in brain"],"prefix":"10.1111","volume":"44","author":[{"given":"Petra","family":"Bonova","sequence":"first","affiliation":[{"name":"Institute of Neurobiology Slovak Academy of Sciences Soltesovej 4\/6 Kosice SK\u2010040 01 Slovakia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Miroslava","family":"Nemethova","sequence":"additional","affiliation":[{"name":"Institute of Neurobiology Slovak Academy of Sciences Soltesovej 4\/6 Kosice SK\u2010040 01 Slovakia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Milina","family":"Matiasova","sequence":"additional","affiliation":[{"name":"Institute of Neurobiology Slovak Academy of Sciences Soltesovej 4\/6 Kosice SK\u2010040 01 Slovakia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Martin","family":"Bona","sequence":"additional","affiliation":[{"name":"Department of Anatomy Faculty of Medicine Pavol Jozef Safarik University Kosice Slovakia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Miroslav","family":"Gottlieb","sequence":"additional","affiliation":[{"name":"Institute of Neurobiology Slovak Academy of Sciences Soltesovej 4\/6 Kosice SK\u2010040 01 Slovakia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2016,10,24]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00018-009-0119-y"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/icb.2010.60"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V93.11.4006"},{"key":"e_1_2_8_5_1","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1016\/S0031-6997(25)01000-2","article-title":"Inhibition of mammalian protein synthesis by antibiotics","volume":"21","author":"Beard N.S.","year":"1969","journal-title":"Pharmacol. 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