Predictors of Reperfusion CBF and its Effects on Outcome After Endovascular Middle Cerebral Artery Occlusion in the SPAN Trial

Submitted by SPAN on Thu, 02/27/2025 - 00:05
Presented by: Takahiko Imai
Affiliation: Massachusetts General Hospital

Background & Aim

・Reperfusion cerebral blood flow (CBF) is critical for stroke outcomes. However, factors influencing Reperfusion CBF and its effect on outcomes remain unclear.

・ The Stroke Preclinical Assessment Network (SPAN) conducted a randomized, controlled, blinded, and highly heterogeneous multi-laboratory trial to identify effective interventions in the stroke animal model.

・Using SPAN MGH data, we examined 1) the predictors of reperfusion CBF and 2) the effect of reperfusion CBF on stroke outcome.

Methods

Reperfusion CBF data was collected from a total of 129 C57 mice after 30 or 60 min transient endovascular filament-induced middle cerebral artery occlusion (MCAO)

1) For predictors of reperfusion CBF, we used 11 independent variables:

Numerical: Age, Weight, Zeitgeber time at MCAO, CBF at post-MCAO, Time at reperfusion (3, 5, 10min) Categorical: Sex, MCAO duration, Treatment group and drug, Admin route, Surgeon, Filament thickness

2) For the association between reperfusion CBF and outcomes, we used:

Day 1 and 2 Weight loss and Neuroscore, Day 2 Lesion volume and Swelling, Day 30 Atrophy, Day 7 and 28 Corner test, 30-day Mortality (Statistic model included observation days, time at reperfusion, and interaction of Reperfusion CBF and time for predicting outcome)

Result

Summary & Conclusion

    Reperfusion CBF increased between 3 and 5 min but not between 5 and 10 min after filament removal.
    In bivariable analysis, Reperfusion CBF was significantly changed by Sex and Circadian stage (active/inactive, and ZT). Male or active circadian phase show low Reperfusion CBF
    In multi-variable analysis, Reperfusion CBF was affected by measurement time of Reperfusion CBF, sex, Circadian stage (ZT), surgeon, CBF at post-MCAO,
    Reperfusion CBF did not predict tissue or behavior outcomes but predicted mortality.
    Lower Reperfusion CBF was associated with higher mortality (hazard ratio 0.96 [0.93 – 0.99] for each 1% reperfusion CBF). The ROC cut-off value for Reperfusion CBF predicting mortality was 79% at 10min after reperfusion.