Ein neues experimentelles Modell zur Untersuchung von spreading depolarizations bei zerebraler Hypoperfusion im gyrenzephalen Gehirn

The effect of cerebral hypoperfusion on the development of Spreading Depolarization (SD) has not yet been determined. Here, we developed a novel swine model of endovascular, intracranial vessel occlusion without acute infarction for simulation of reversible cerebral hypoperfusion.

Twelve female landrace swine were anesthetized and mean arterial blood pressure was targeted at 60-80mmHg. Bilateral iliac artery punctures were performed and two 8F angiographic sheaths were inserted. Using 2D angiographic guidance, balloon catheters were positioned within both carotid arteries directly proximal to the main feeding trunk of the porcine rete mirabilis. Next, the animals were repositioned prone and a bilateral craniectomy was performed. The dura was excised and a Laser Speckle Imaging (LSI) device was positioned for continuous recording of cortical perfusion. With angiographic control, a baseline LSI perfusion measurement (60 min) was obtained, followed by LSI during unilateral (60 min) and bilateral (60 min) occlusion and subsequent reperfusion (60 min).

In 9/12 animals (75%), a total number of 51 SD-associated hemodynamic response patterns were recorded during a recording time of 2.880 hours. The mean SD propagation velocity was 3.2±0.9mm/min across a propagation area of 90±40mm2. The mean SD numbers were 0.42±1.7 SDs/h at baseline, 0.17±0.39 SDs/h during unilateral occlusion, 2.58±3.5 SDs/h during bilateral occlusion and 1.08±2.8 SDs/h during reperfusion (p=0.058, one way ANOVA).

Endovascular balloon occlusion proximal to the porcine rete mirabilis can reliably trigger SD activity in the gyrencephalic brain, which may help to unravel the pathophysiology of TIA in patients suffering chronic cerebral ischemia.