Blood as the carrier of ischemic tolerance in rat brain

Abstract

This study provides clear evidence that the factor inducing tolerance to ischemia is transmitted via the circulating blood. By using the remote ischemia and the cross-circulation model, the tolerance to ischemia was transmitted from donor to recipient. For this study, the following experimental groups were designed: I, sham control group; II, group of tolerant hindlimb tourniquet-treated rats; III, positive control group; IV, control for cross-circulation influence; preconditioned animals: V, tolerant animals subjected to middle cerebral artery occlusion (MCAO); VI, tolerant animals cross-circulated with SHC, followed by MCAO; VII, SHC animals cross-circulated with tolerant animals and subsequently subjected to MCAO; VIII, tolerant animals cross-circulated with ischemic rats, followed by MCAO; IX, SHC animals cross-circulated with ischemic animals and subjected to MCAO; postconditioned animals: X, ischemic animals treated with a remote limb tourniquet; XI, ischemic animals cross-circulated with SHC control rats; and XII, ischemic animals cross-circulated with tolerant rats. Results confirmed that remote ischemia induced reduction of infarct volume in the preconditioned (V, 60%) as well as in the postconditioned group (X, 52%). Significant diminution was also observed in group XII (56.6%). In the preconditioned group, decreased infarct volume was detected in groups VI and VII (about 65%) and in group IX (about 50%). The greatest infarct reduction (84%) was induced by the presence of ischemic blood in a tolerant rat before ischemia induction. In summary, the factor inducing tolerance to ischemia is generated by remote ischemia and by ischemia itself; from the site of origin to the rest of the body, it is transported by the systemic blood circulation and can be transferred from animal to animal. The effect of conditioning with two different ischemic events (brain and hindlimb ischemia) led to a cumulative, stronger tolerance response.

Keywords: brain ischemia; cross-circulation; ischemic tolerance; remote tolerance; tolerance-inducing factor.