Temporal changes in sensitivity of rats to cerebral ischemic insult

Abstract

Object. Experimental rat models are often used to study cerebral ischemia, yet rats are nocturnal animals that have activity cycles that are the opposite of those of humans. In the following study the authors examined the circadian rhythm of sensitivity to an ischemic insult in rats by using an intraluminal thread technique to produce reversible middle cerebral artery occlusion.Methods. Ischemia (2 hours of blockage followed by 22 hours of reperfusion) was induced in rats according to the 24-hour clock at either 100, 400, 700, 1000, 1300, 1600, 1900, or 2200 hours (11–14 rats per time period). The rat brains were removed, coronally sectioned, stained with 2,3,5-triphenyltetrazolium chloride and analyzed using commercially available software. Analysis of variance and cosinor-rhythmometry statistical tests were used for analysis of data. The time of day when the ischemic infarct was induced had a significant (p = 0.011) influence on the volume of the lesion. The volume of total brain infarct produced at 400 hours (7.65 ± 1.31%) was more than three times greater than the volume produced at 1600 hours (2.1 ± 0.34%). Cosinor-rhythm analysis indicated a peak occurrence of infarct volume at 6:02 (95% confidence interval 5:49–6:16). The size of the infarct correlated with core body temperature rhythms, which varied by 1.3 ± 0.62°C (mean ± standard deviation).Conclusions. Circadian rhythms, as well as the reversed natural body rhythms of the rat compared with humans, should be considered when extrapolating data to human or other animal studies. Temporal rhythms may also provide information concerning the cascading disease processes associated with cerebral ischemia.