Ischemic preconditioning and brain tolerance: temporal histological and functional outcomes, protein synthesis requirement, and interleukin-1 receptor antagonist and early gene expression

A short duration of ischemia (ie, ischemic preconditioning [PC]) can provide significant brain protection to subsequent ischemic events (ie, ischemic tolerance [IT]). The present series of studies was conducted to characterize the temporal pattern of a PC paradigm, to systematically evaluate the imp...

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Bibliographic Details
Published in:Stroke (1970) 1998-09, Vol.29 (9), p.1937-1951
Main Authors: Barone, F C, White, R F, Spera, P A, Ellison, J, Currie, R W, Wang, X, Feuerstein, G Z
Format: Article
Language:English
Subjects:
Animals
Arterial Occlusive Diseases - physiopathology
Behavior, Animal
Brain - blood supply
Brain - cytology
Brain Chemistry
Brain Ischemia - physiopathology
Cell Death
Cerebral Infarction - physiopathology
Cerebrovascular Circulation
Cerebrovascular Disorders - physiopathology
Forelimb - innervation
Forelimb - physiology
Gene Expression
Hindlimb - innervation
Hindlimb - physiology
Ischemic Preconditioning
Neurologic Examination
Neurons - cytology
Rats
Rats, Inbred SHR
Receptors, Interleukin-1 - antagonists & inhibitors
Receptors, Interleukin-1 - genetics
RNA, Messenger - analysis
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Summary:A short duration of ischemia (ie, ischemic preconditioning [PC]) can provide significant brain protection to subsequent ischemic events (ie, ischemic tolerance [IT]). The present series of studies was conducted to characterize the temporal pattern of a PC paradigm, to systematically evaluate the importance of protein synthesis in PC-induced IT, and to explore candidate gene expression changes associated with IT. Temporary middle cerebral artery occlusion (MCAO) (10 minutes) was used for PC. Various periods of reperfusion (ie, 2, 6, and 12 hours and 1, 2, 7, 14, and 21 days) were allowed after PC and before permanent MCAO (PMCAO) (n=7 to 9 per group) to establish IT compared with non-PC (sham-operated) rats (n=22). Infarct size, forelimb and hindlimb motor function, and cortical perfusion (laser-Doppler flowmetry; n=9 per group) were measured after PMCAO. The effects of the protein synthesis inhibitor cycloheximide administered just before PC (n= 13 to 17) or administered long after PC but just before PMCAO (n=7 to 8) on IT were also determined. Interleukin- receptor antagonist mRNA (reverse transcriptase and polymerase chain reactions [n=20] and Northern analysis [n=50]) and protein expression (immunohistochemistry [n=16]) after PC and early response gene expression (Northern analysis [n=16]) after PMCAO in PC animals were determined. Hemispheric infarct was significantly (P
ISSN:0039-2499
1524-4628
DOI:10.1161/01.str.29.9.1937