Reinduced expression of developmental proteins (nestin, small heat shock protein) in and around cerebral arteriovenous malformations

Intermediate filament (IF) nestin and small heat shock protein (sHSP) are developmentally regulated proteins. Nestin is highly expressed on proliferating neuro-epithelial stem cells of the developing central nervous system (CNS). During the developmental neurulation stage, nestin is replaced by mature neuronal (neurofilament) or glial cell-specific IFs (glial fibrillary acidic protein, GFAP). Several pathologic states induce astrocytes to synthesize nestin transiently in the mature brain. However, the exact nature of the embryonic conversion from nestin to mature cytoskeleton is unclear. In an attempt to define the effect of ischemic hemodynamic stress caused by cerebral arteriovenous malformation (AVM) on the brain parenchyma, we examined the synthesis and cellular distribution of sHSP and nestin in vascular elements of AVMs and in the gliotic area surrounding AVMs. Ten consecutively collected surgical specimens meeting the histological criteria for AVM were immunohistochemically stained using primary antibodies for nestin, HSP27 and αB-crystallin. Nestin, HSP27 and αB-crystallin mRNA expressions were examined by reverse transcriptase-polymerase chain reaction (RT-PCR). Nestin expression is reinduced not only in reactive astrocytes, but also in endothelial cells in the surrounding gliotic tissue of the cerebral AVM. These cells also expressed sHSP (HSP27, αB-crystallin) that maintain the integrity of the IF network and prevent unfolding of cellular proteins induced by various stresses. RT-PCR showed the increased expression of sHSP and nestin mRNA in the AVM specimens. These results indicate that embryonic reversion of the mature cytoskeleton to nestin and the increased expression of sHSP in response to cerebral injury are associated with increased wall tension caused by dilating AVM vessels and with the hemodynamic stress that surrounds AVMs.