Is there a zone of vascular vulnerability in the fetal brain stem?

The pattern of malformations in congenital anomalies such as Möbius syndrome and following prenatal cocaine exposure suggests that there is a zone of vascular vulnerability or ischemic sensitivity in the paramedian region of the developing brain stem. In the present study, postmortem examination of the brain of an infant with Möbius syndrome revealed mineralized foci concentrated in paramedian wedge-shaped areas of the pontine and medullary tegmentum. We also examined the development of brain stem vasculature in the rat at the light and ultrastructural level to determine whether anatomical features of the paramedian brain stem region could contribute to elevated incidence of vascular accidents in that zone. Several observations of relevance to the question of vascular vulnerability of the midline were made. Firstly, and as previously noted by other authors, the brain stem midline remains avascular for protracted periods during fetal life. We propose that the inability of vessels in the paramedian region to anastomose across the avascular midline gives rise to paramedian watershed zones that could be vulnerable to ischaemia in the event of hypoperfusion due to teratogenic action. Secondly, we studied the development of cytochrome oxidase activity in the fetal brain stem and noted high oxidative metabolic activity of the somatic efferent nuclei in the paramedian region, which could render their constituent neurons particularly susceptible to hypoxia. Thirdly, our ultrastructural examination revealed large amounts of extracellular space surrounding paramedian pontine vessels in comparison to laterally placed vessels, although there was no significant difference between the vessels of the two regions in tight junction length and endothelial thickness. We propose that the greater proportion of unoccupied extracellular space surrounding medial vessels may contribute to poorer support of these vessels in ischemic/reperfusion episodes. This poor support could in turn give rise to an increased risk of hemorrhage.