Prereperfusion flushing of ischemic territory: a therapeutic study in which histological and behavioral assessments were used to measure ischemia-reperfusion injury in rats with stroke

Object. In ischemic stroke, the ischemic crisis activates a cascade of traumatic events that are potentiated by reperfusion and eventually lead to neuronal degeneration. The primary aim of this study was to investigate a procedure that could minimize this damage by interfering with the interactions between reestablished blood flow and ischemically damaged tissue, as well as by improving regional microcirculation. Methods. Using a novel hollow filament, the authors flushed the ischemic territory with heparinized saline before vascular reperfusion after occlusion of the middle cerebral artery (MCA). The results demonstrate a statistically significant (p < 0.001) reduction in infarct volume (75%; from 45.3 +/- 3.6% to 11.4 +/- 1.7%, determined with Nissl staining) in rats in which a 2-hour MCA occlusion was followed by a 48-hour reperfusion. Infarction and neuronal degeneration were confirmed using silver staining, which revealed a significantly larger infarct (36.3%, p < 0.05) than that detected with Nissl staining. The long-term neuroprotection of the prereperfusion flushing was also evaluated. This was determined by a series of motor behavior tasks (foot placing parallel bar traversing, rope and ladder climbing) performed up to 28 days after reperfusion. Motor deficits were found to be significantly ameliorated in animals that underwent the flushing procedure (p < 0.001). In addition, neurological outcome was also improved significantly (p < 0.001) in the same animals. Conclusions. These results indicate that interaction between reperfusion and the metabolically and biochemically compromised tissue could be interrupted by the prereperfusion flushing procedure, which could lead to a reduction in brain injury from stroke. Mechanical reopening of the cerebral occlusion with local flushing and isolated reperfusion of the regionally injured brain might offer new treatment options for patients with stroke.