Short Period of Early Reperfusion Aggravates Blood–Brain Barrier Dysfunction During Permanent Focal Ischemia in Rats

Abstract

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.

Neuroprotective Effects of BHDPC, a Novel Neuroprotectant, on Experimental Stroke by Modulating Microglia Polarization

“…The restrictive nature of the BBB is specifically due to tight junctions between adjacent endothelial cells, specifically occludin and ZO-1 . It has been reported that there is a direct correlation between the levels of tight junction proteins and the extent of endothelial barrier permeability, and the discontinuous appearances of tight junctions on the cell periphery provide a further explanation for the compromised BBB after cerebral ischemia. , Therefore, we next explored the role of BHDPC in MCAO-induced changes in tight junction protein characteristics, including expression and localization. First, as shown in Figures E and F, levels of both ZO-1 and occludin were significantly reduced in the MCAO brains (both p < 0.01 versus the sham group).…”

The role of thrombin in early-onset seizures

“…Our data are in agreement with these studies demonstrating the generation of epileptiform activity due to thrombin application in the blood plasma media. Recent findings suggest a significant increase in the thrombin level in the brain tissue caused by the enhancement of BBB permeability during pathological conditions (Woitzik et al, 2011 ; Isaev et al, 2015 ). Thrombin, through its major receptor in the neural tissue, protease-activated receptors 1 (PAR 1), produces epileptogenesis by the escalation of brain damage, induction of seizures, inflammation, and neurogenesis (Rohatgi et al, 2004 ).…”

Administration of a second generation perfluorochemical in combination with hyperbaric oxygenation does not provide additional benefit in a model of permanent middle cerebral artery occlusion in rats

“…The suture was advanced with special care not to enter the pterygopalatine artery until an abrupt drop of the LDF signal indicated MCA occlusion. The suture was fixed to avoid shifting (Woitzik et al, 2011 ) and the neck incision was closed. After removing the LDF fibers from the skull anesthesia was discontinued and the animals were allowed to recover.…”