A photothrombotic ring stroke model in rats with sustained hypoperfusion followed by late spontaneous reperfusion in the region at risk

In clinical thromboembolic stroke, spontaneous late recanalization is a com mon feature, but one which has been very sparsely studied experimentally. T his study aimed at enabling the study of spontaneous reperfusion and explor ing its consequences by modifying a recently developed photothrombotic-stro ke model that focuses on the region-at-risk located within an ischemic ring -locus. The exposed crania of male Wistar rats (280-340 g) were subjected t o a ring-shaped (5.0 mm outer diameter and 0.35 mm thick) laser-irradiation beam (514.5 nm; 0.89 W/cm(2)) for 2 min simultaneously with intravenous er ythrosin B (17 mg/kg) infusion for 30 s. Transcardial carbon-black perfusio n experiments revealed a ring-shaped cortical perfusion deficit at 4 h post -irradiation, which progressively increased at 10, 24, and 48 h, at which t ime the whole region-at-risk was pale with single distal branches of the mi ddle cerebral artery being extensively narrowed, but not occluded. At 72 h, spontaneous reperfusion was observed in the region-at risk, which was even more pronounced at 7 and 28 days. Cortical cerebral blood flow (cCBF), mea sured by laser-Doppler flowmetry, was distinctly reduced at 2 min post-irra diation and further decreased slightly during 4 h of recording to ca. 24% o f baseline values at the ring locus and 40% in the region-at-risk. In the r egion-at-risk, cCBF flow values were 23-30% of the baseline at 24-48 h post -irradiation, followed by a relative cCBF increase to 71 and 77% at 72 and 96 h post-irradiation. Brain water content in the ischemic part of the cort ex increased steadily from 4 to 48 h post-irradiation; at 72 h, it leveled off and returned to control values at 7 days. In conclusion, by employing a laser beam in the shape of a thin ring, critically sustained cCBF reductio n was followed by late, consistent spontaneous reperfusion in the region-at -risk in this novel photochemically induced stroke-in-evolution model.