Adv Exp Med Biol. 2026;1498:213-217. doi: 10.1007/978-3-032-10389-5_25.
ABSTRACT
Current treatments for ischemic stroke are not focused on microvascular cerebral blood flow (mvCBF), which actually delivers oxygen to tissue and is significantly impaired during a stroke. We previously showed that drag-reducing polymers (DRPs, 2 μg/ml), injected just after permanent middle cerebral artery occlusion (pMCAO) in rats, effectively restored mvCBF and tissue oxygenation. The aim of this work was to assess the efficiency of DRPs administered at various time points post-onset. DRPs (2 μg/ml) or saline was i.v. injected 0.5, 3, or 6 h after pMCAO induction in rats (n = 10/group). Laser speckle contrast imaging (LSCI) was used to evaluate regional cerebral blood flow in the parietal cortex and estimate the ischemic area. In vivo 2-photon laser scanning microscopy (2PLSM) was used to assess the effects on mvCBF and tissue hypoxia (NADH). Two-way ANOVA for multiple comparisons was used to test intergroup differences with the statistical significance level set at p < 0.05. PMCAO progressively decreased cortical mvCBF, causing tissue hypoxia (p < 0.05). Intravenous administration of DRPs at 0.5, 3, and 6 h post-pMCAO effectively improved cerebral microcirculation and oxygen delivery to tissue in a time-dependent manner compared to the saline-treated group (p < 0.05). DRPs efficacy reduced with the time of application from 0.5 to 6 h after pMCAO but remained significant compared to the saline-treated group (p < 0.05). DRPs augment collateral microcirculatory flow through leptomeningeal and pial anastomoses that interconnect the middle, anterior, and posterior cerebral artery watershed territories. We demonstrated that DRPs can be used as a new effective adjunct therapy for ischemic stroke, even without reperfusion and after delayed administration following the stroke onset.
PMID:41577920 | DOI:10.1007/978-3-032-10389-5_25