A descriptive synthesis of our results will be presented. We plan to report data on neurobehavioral performance, and any other continuous data, with normalized mean difference (NMD) as the effect-size measure with 95% confidence intervals (CIs). This is considering that data from sham and uninjured animal models are available or can be easily inferred. If there are no data available on sham animals or it cannot be inferred, we will report neurobehavioral results with standardized mean difference (SMD). In a single study, different tests can be conducted to assess neurobehavioral performance in the same cohort of animals. To synthesize the overall neurobehavioral performance, we will combine data from neurobehavioral tests into a single “nested” outcome, when possible, using a method previously described by members of our research team (Vesterinen 2014) [34]. Mortality data, as well as any other dichotomous data, will be reported with risk ratios (RR) as the effect-size measure and 95% confidence intervals (95% CIs).

If appropriate, we will pool data from our primary and secondary outcomes using the inverse of the variance with random-effects models. We will need at least 3 studies using similar animal models, transfusion strategy and comparator to conduct a meta-analysis. Cochrane Review Manager (RevMan) version 5.3 (The Cochrane Collaboration, Copenhagen, Denmark, 2014) will be used. Statistical heterogeneity will be evaluated using the I2 index and classified as very low (0–25%), low (25–50%), moderate (50–75%), or high (> 75%) [35]. Funnel plots will be used for the evaluation of potential publication bias for neurobehavioral outcome and mortality results with additional analysis for each type of brain injury. Subgroup analyses will be conducted when possible using the following: mammal class orders (primates vs. rodents vs. all others), transfusion thresholds (restrictive vs. liberal strategies), the presence of co-interventions, induced anemia during preparation (hemorrhage vs. hemodilution vs none), type of neurocritical condition (TBI vs. ischemic stroke vs. ICH vs. SAH) and risk of bias (high/unclear risk of bias vs. low risk of bias).

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