Preconditioning with CpG-ODN1826 reduces ischemic brain injury in young male mice: a replication study

Earlier studies established that ischemic tolerance can be induced in the brain using various strategies. An earlier study demonstrated that preconditioning with the toll-like receptor 9 ligand, CpG oligodeoxynucleotides (ODN), protects the brain against ischemic damage. To increase the potential translational value of the previous study, the goal of the present study was to replicate this earlier finding in a different animal cohort at a different site. In addition to these replication studies, following the Stroke Treatment Academic Industry Roundtable (STAIR) guidelines, we also conducted studies to evaluate the protective effect of CpG-ODN 1826 preconditioning on cerebral ischemic damage in ovariectomized (Ovx) female animals. Young male and female mice were treated with CpG-ODN 1826 or control ligand 3 days prior to the induction of transient (60 min) cerebral ischemia using a middle cerebral artery occlusion (MCAO) model. Infarct size was evaluated at ~24 h post-MCAO. We were able to replicate earlier findings that preconditioning with a low dose (20 μg/mouse) of CpG-ODN 1826 was able to lower cerebral ischemic damage in young male mice. However, we did not see any protective effect of low dose CpG-ODN 1826 preconditioning against cerebral ischemic damage in young Ovx female mice. Our study independently confirms the protective effect of CpG-ODN 1826 in inducing cerebral ischemia tolerance in male but not in Ovx female mice. Our study also demonstrates the feasibility of conducting such replication studies in rodent models of transient stroke.