IS THERE A ZONE OF VASCULAR VULNERABILITY IN THE FETAL BRAIN-STEM

The pattern of malformations in congenital anomalies such as Mobius sy ndrome and following prenatal cocaine exposure suggests that there is a zone of vascular vulnerability or ischemic sensitivity in the parame dian region of the developing brain stem. In the present study, postmo rtem examination of the brain of an infant with Mobius syndrome reveal ed mineralized foci concentrated in paramedian wedge-shaped areas of t he pontine and medullary tegmentum. We also examined the development o f brain stem vasculature in the rat at the light and ultrastructural l evel to determine whether anatomical features of the paramedian brain stem region could contribute to elevated incidence of vascular acciden ts in that zone. Several observations of relevance to the question of vascular vulnerability of the midline were made. Firstly, and as previ ously noted by other authors, the brain stem midline remains avascular for protracted periods during fetal life. We propose that the inabili ty of vessels in the paramedian region to anastomose across the avascu lar midline gives rise to paramedian watershed zones that could be vul nerable to ischaemia in the event of hypoperfusion due to teratogenic action. Secondly, we studied the development of cytochrome oxidase act ivity in the fetal brain stem and noted high oxidative metabolic activ ity of the somatic efferent nuclei in the paramedian region, which cou ld render their constituent neurons particularly susceptible to hypoxi a. Thirdly, our ultrastructural examination revealed large median pont ine vessels in comparison to laterally placed vessels, although there was no significant difference between the vessels of the two regions i n tight junction length and endothelial thickness. We propose that the greater proportion of unoccupied extracellular space surrounding medi al vessels may contribute to poorer support of these vessels in ischem ic/reperfusion episodes. This poor support could in turn give rise to an increased risk of hemorrhage. (C) 1997 Elsevier Science Inc.