Abstract WP326: Cortical Border Zones Are More Vulnerable to Spreading Depression-Induced Capillary Flow Disturbances

Abstract

Cortical spreading depression (SD) is a major metabolic challenge to the brain and is followed by a unique hemodynamic response. It has been suggested that the oligemic phase of this response is accompanied by a mild to moderate capillary dysfunction. To test this hypothesis, we directly investigated microcirculatory flow changes during and after SD at the territory of major arteries as well as their hemodynamically vulnerable watershed zones. Swiss mice (n=6) under isoflurane anesthesia were tracheotomized, mechanically ventilated, and imaged under two-photon microscopy through a closed cranial window. Mean transit time (MTT), capillary transit time heterogeneity (CTH) and relative transit time heterogeneity (RTH) were calculated based on an indicator-dilution method using intravenous boluses of Texas-red dextran fluorescent dye (70,000 MW; 0.5%). Boluses were performed at the steady-state and 1 min, 5 min and 30 minutes after potassium chloride-induced SD. MTT, CTH, and RTH were estimated within the territory and border zone of major arteries to reveal any regional differences. Physiological parameters were monitored and kept within normal limits throughout the experiments. Both MTT and CTH increased following SD in the territorial zone from 1.07±0.03 to 1.67±0.15 s (mean±SEM;p<0.01) and from 0.51±0.03 to 0.94±0.07 s (mean±SEM;p<0.01), respectively. However, RTH was only mildly increased in this region from 0.49±0.04 to 0.59±0.06 (p=0.03). In the watershed area, all three parameters showed a more prominent increase following SD and RTH rose from 0.64±0.06 to 1.25±0.22 at 30 minutes (p=0.04). These findings provide direct experimental evidence for prolonged capillary flow disturbances induced by cortical SD, which may account for some lasting neurological symptoms after aura. The particular vulnerability of border zones to SD-induced flow disturbances may be involved in the pathogenesis of some of the white matter MRI lesions observed in migraineurs.