Hyperperfusion profiles after recanalization differentially associate with outcomes in a rat ischemic stroke model

Area of Science:

• Neuroscience
• Radiology
• Biomedical Engineering

Background:

• Successful mechanical thrombectomy for ischemic stroke can be hindered by "futile recanalization," leading to poor prognoses.
• Factors like post-recanalization perfusion deficits, delays in treatment, and sex effects are hypothesized contributors.
• Acute multiparametric imaging for these assessments remains a clinical challenge.

Purpose of the Study:

• To investigate the relationships between post-recanalization perfusion parameters, sex, and stroke outcome in an experimental model.
• To utilize translational magnetic resonance imaging (MRI) and behavioral testing to analyze cerebral ischemia-reperfusion injury.
• To apply multi-model inference analyses for a comprehensive understanding of the contributing factors.

Main Methods:

• Male and female rats underwent transient middle cerebral artery occlusion (MCAO) for 45 or 90 minutes.
• Diffusion, T2-weighted, and perfusion-weighted MRI were performed at occlusion, 0.5 hours, and 4 days post-recanalization.
• Lesion analysis included tracking tissue fate, relative regional cerebral blood flow (rrCBF), and relative regional cerebral blood volume (rrCBV), validated by histology.

Main Results:

• Recanalization led to acute-to-subacute lesion volume reduction, more pronounced in females.
• Post-ischemic hyperperfusion (increased rrCBF and rrCBV) was observed, augmenting over time, particularly in males.
• Delayed tissue injury correlated with higher ratios of hypoperfused voxels early post-recanalization.
• Increased rrCBF was associated with lesion growth, while increased rrCBV correlated with lesion reduction.
• Sex-specific differences in post-ischemic hyperperfusion were noted, impacting outcomes differently based on the perfusion parameter.

Conclusions:

• Post-recanalization perfusion dynamics, including hyperperfusion, play a critical role in stroke outcome.
• Sex influences the development and impact of post-ischemic hyperperfusion.
• The specific perfusion parameter (rrCBF vs. rrCBV) is crucial in determining whether hyperperfusion is beneficial or detrimental.