Short period of early reperfusion aggravates blood-brain barrier dysfunction during permanent focal ischemia in rats.

Unintentional reperfusion is considered a complication in various experimental models of focal brain ischemia. In the present study, we evaluated whether short intermittent reperfusion affects ischemic brain damage and blood-brain barrier (BBB) integrity in a model of permanent focal ischemia. Focal brain ischemia was induced in male Sprague-Dawley rats using the filament method. A 20-s reperfusion period was allowed 0.5, 2, or 10 min after thread occlusion of the middle cerebral artery. In control animals, the transient reperfusion episode was omitted. The infarct volume and extent of swelling was examined 24 h after permanent thread occlusion. Immunohistochemical staining for thrombin extravasation was performed. Transient reperfusion early after thread occlusion augmented brain swelling (control, 12.4 ± 8.5%; reperfusion after 0.5 min, 24.7 ± 7.0%; after 2 min, 36.7 ± 4.8%; after 10 min, 33.8 ± 4.9%*; *p < 0.01 vs. control) and significantly enhanced leakage of the plasma protein thrombin, whereas the ischemic volume was unaffected. Early intermittent reperfusion may be responsible for increased BBB disruption in permanent ischemia. Similar reperfusion episodes during early ischemia sequelae in patients-due to incomplete adherence or distal movements of a clot-may be causative for increased BBB damage, more severe edema, and potentially hemorrhagic transformation.