Expression of vascular endothelial growth factor in pediatric and adult cerebral arteriovenous malformations: an immunocytochemical study

Abstract

Children and adults may differ with respect to their cerebral vasculature in both normal and pathological states. The authors have identified four pediatric patients in whom a cerebral arteriovenous malformation (AVM) recurred after surgery for removal of the AVM and in whom a normal postoperative angiogram had been obtained. This phenomenon has not been observed in adults. The propensity to regrow a cerebral AVM may reflect a less mature cerebral vasculature and a disregulated angiogenic process. Recently, attention has focused on vascular endothelial growth factor (VEGF) as a possible general mediator of angiogenesis in development and neoplasia. A retrospective immunocytochemical analysis of VEGF expression in AVM tissue was conducted to test the hypothesis that VEGF expression may be found in association with the regrowth of AVMs. The results demonstrate a high degree of astrocytic VEGF expression in four (100%) of four specimens from the initial operation in the children with recurrent AVMs as compared to one (14%) of seven nonrecurrent AVMs in the pediatric and two (25%) of eight adult specimens. All of the specimens from the first operation of the recurrent group demonstrate a clear association of cellular immunoreactivity to the abnormal blood vessels, a relationship that was not observed in the specimens from the nonrecurrent groups. These observations indicate that a humoral mechanism mediated by VEGF may play a role in AVM recurrence.

Nestin Expression in Vascular Malformations: A Novel Marker for Proliferative Endothelium

“…3,9,15,18,20) The underlying developmental and pathogenetic mechanisms of these malformations are not completely understood, but may involve the proliferative and angiogenic capacities of the endothelium. 7,13,21,23) Nestin is one of the intermediate filaments abundantly produced in the developing central nervous system and somites in the embryonic stage of rodents, and is used as a marker of neuroepithelial stem cells. 11,28) Expression of nestin is high in the cerebrum of the developing mouse embryo, peaking at embryonic day 15, and declines with further growth.…”

Cerebral arteriovenous malformations. Part 1: cellular and molecular biology

“…10,51,52,84,94,95,101,137 Vascular endothelial growth factor is expressed at high levels during embryonic development, but its expression is normally suppressed in the adult cerebral vasculature. 114 Interestingly, VEGF is highly expressed in children with recurrent cerebral AVMs.…”

Vascular Endothelial Growth Factor Induces Abnormal Microvasculature in the Endoglin Heterozygous Mouse Brain

“…Using adenoviral vector delivery VEGF (AdhVEGF) in the mouse brain, we have successfully developed a focal brain angiogenesis model (Xu et al, 2003). Clinical studies demonstrate that VEGF is greatly increased in hemorrhagic stroke, cerebral ischemia, Alzheimer disease, and human BAVM (Hayashi et al, 2003;Sonstein et al, 1996;Tarkowski et al, 2002;Zhang et al, 2000). However, the nature of VEGF-induced angiogenesis in the normal adult brain is unknown.…”