Abstract WP342: Beyond Recanalization: Rescuing Cerebral Microcirculation by Drag-Reducing Polymers after Experimental Ischemic Stroke

Introduction: Reperfusion therapies, such as thrombolysis with tissue plasminogen activator and endovascular thrombectomy, are the cornerstone of acute stroke treatment, aiming to restore blood flow to the ischemic brain. However, even after successful recanalization of large vessels, many patients experience incomplete recovery due to persistent microvascular dysfunction. This can manifest as “no-reflow” phenomenon, endothelial dysfunction, inflammation, and reperfusion injury, all worsening tissue damage and outcomes. Drag-reducing polymers (DRP), high-molecular-weight macromolecules given intravenously at nanomolar levels, improve microvascular perfusion by lowering resistance and optimizing hemodynamics. This study assessed high-molecular-weight DRP time-dependent efficacy in restoring cerebral microcirculation, reducing infarct volume, and mitigating blood-brain barrier (BBB) damage in a rat transient middle cerebral artery occlusion (tMCAO) model. Methods: Adult Wistar rats underwent 3.5-hour monofilament tMCAO with reperfusion. Subjects were randomized to intravenous DRP (5 ppm) or saline at 1 or 3 hours post-occlusion. At baseline, immediately, and 3.5 hours after tMCAO, laser speckle contrast imaging (LSCI) quantified cortical cerebral blood flow (CBF). At 24 hours, neurobehavioral deficits were assessed (modified Bederson scale, limb asymmetry, rotarod). Evans Blue (2%, 4 mL/kg i.v.) quantified BBB permeability via spectrofluorometry (μg/g tissue). Infarct volume was measured by 2,3,5-triphenyltetrazolium chloride (TTC) staining with edema correction using ImageJ. Differences were analyzed by two-way ANOVA with Tukey's post-hoc; data as mean ± SEM, p<0.05. Results: tMCAO reduced CBF by 62.4±5.1% (p<0.001), causing BBB leakage (8.7±0.9 μg/g), infarct (215.8±18.3 cu mm), and deficits (score 12.5±1.1). DRP improved CBF (1h: 58.3±4.2% baseline; 3h: 49.1±3.8%; vehicle: 37.6±3.2%; both p<0.01). Infarct decreased (1h: 112.3±12.5 cu mm, p<0.01; 3h: 148.7±14.1 cu mm, p<0.05). BBB permeability reduced (1h: 4.1±0.5 μg/g; 3h: 5.8±0.6 μg/g; both p<0.01). Scores improved (1h: 5.2±0.8; 3h: 7.1±0.9; both p<0.05). Efficacy was time-dependent (1h>3h, p<0.05). Conclusion: DRP, administered up to 3 hours post-tMCAO, enhances cerebral microcirculation and collateral flow, limits infarct and BBB damage, and improves outcomes, positioning it as a promising adjunct therapy for thrombolysis and thrombectomy.