Cerebral Blood Flow Heterogeneity in Preterm Sheep: Lack of Physiological Support for Vascular Boundary Zones in Fetal Cerebral White Matter

Periventricular white matter (PVWM) injury is the leading cause of chronic neurological disability in survivors of prematurity. To address the role of cerebral ischemia in the pathogenesis of this injury, we tested the hypothesis that immaturity of spatially distal vascular “end” or “border” zones predisposes the PVWM to be more susceptible to falls in cerebral blood flow (CBF) than more proximal regions, such as the cerebral cortex. We used fluorescently-labeled microspheres to quantify regional CBF in situ in the 0.65 gestation fetal sheep in histopathologically-defined 3-dimensional regions by means of post hoc digital dissection and co-registration algorithms. Basal flow in PVWM was significantly lower than gyral white matter and cerebral cortex, but was equivalent in superficial, middle and deep PVWM. Absolute and relative CBF (expressed as percentage of basal) CBF did not differ during ischemia or reperfusion between the PVWM and more superficial gyral white matter or cortex. Moreover, CBF during ischemia and reperfusion was equivalent at three distinct levels of the PVWM. Absolute and relative CBF during ischemia and reperfusion was not predictive of the severity of PVWM injury, as defined by TUNEL staining. However, the magnitude of ischemia to the cerebral cortex directly correlated with lesion severity ( r = −0.48, p