Blood cells serve as a source of factor-inducing rapid ischemic tolerance in brain.
Eur J Neurosci
; 44(11): 2958-2965, 2016 12.
Article
em En
| MEDLINE
| ID: mdl-27706857
ABSTRACT
Ischemic tolerance (IT) has gained attention as an attractive strategy for improving stroke outcome. Recently, it was shown that signal responsible for rapid IT induction (tolerance induction factor - TIF) is transmitted via circulating blood. In this study, we have hypothesized about the role of the blood cell compartment in TIF production. We used hind-limb ischemia to generate TIF as a rapid preconditioning against transient middle cerebral artery occlusion (MCAO). The essential properties of protein synthesis inhibitors actinomycin D and cycloheximide were utilized to obtain the following results:
(i) TIF is proteinaceous. Hind-limb ischemia mediates gene expression followed by translation, resulting in the production of TIF. Blocking of each of these two steps in protein synthesis resulted in rapid infarct evolution (281.5 ± 23.37 and 330.4 ± 71.8 mm3 , respectively). (ii) Tourniquet-treated muscle is not a source of TIF. Actinomicine D injected into rat prior to tolerance induction significantly suppressed RNA synthesis in blood cells and muscle tissue. Cross-circulation of those rats (donors) with control animals (recipients) did not mediate significant infarct reduction (272.9 ± 12.45 mm3 ), even when hind-limb ischemia was performed before MCAO in the recipient (223.2 ± 37.51 mm3 ). (iii) Blood cells serve as a source of TIF. Preischemic transfusion of plasma-free, protein-synthesis-inactive blood cells, which were obtained from tolerant animals did not reduce infarct volume in recipients (131 ± 16.1 mm3 ) in a range comparable with their protein-synthesis-active counterparts (17.2 ± 12 mm3 ). We can conclude that blood cells are associated with the induction of rapid IT via production of a bioactive proteinaceous substance.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Células Sanguíneas
/
Precondicionamento Isquêmico
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Infarto da Artéria Cerebral Média
Limite:
Animals
Idioma:
En
Ano de publicação:
2016
Tipo de documento:
Article