Background: Impairment of the blood–brain barrier (BBB) after cerebral ischemia leads to extravasation of plasma constituents into the brain parenchyma and is associated with a larger final lesion volume and more negative outcome. Hypothesis: Our hypothesis was that an opening in the BBB leads to a larger final lesion volume and a more severe stroke. Here we explored that hypothesis by selectively altering the permeability of the BBB while simultaneously inducing cerebral ischemia. Results: We first looked at the time course of BBB impairment after transient middle cerebral artery occlusion (MCAO) in mice. An initial BBB impairment was observed at 4–8 hours and a second impairment at 12–16 hours after reperfusion. No EB extravasation was detected at 8–12 hours. We then manipulated the permeability of the BBB after MCAo using hydrodynamic delivery of claudin-5 small interfering RNA (siRNA), transcranial magnetic stimulation (TMS), intracarotid injection of hypertonic arabinose, and intraventricular infusion of Pigment epithelium- derived factor (PEDF). Opening the BBB with hypertonic arabinose led to a larger final lesion volume in mice, and the lesion volume correlated with the size of the opening in the BBB induced by arabinose. Claudin-5 siRNA, TMS, and PEDF had no effect on final lesion volume. Conclusion: We found that an early opening in the BBB had a detrimental effect on the progression of stroke and lead to a larger final lesion volume in our animal model.
Wir untersuchten den Effekt, den die offene Blut-Hirn-Schranke auf die Läsionsgröße nach zerebraler Ischämie hatte.
