Pathogenesis of cerebral malformations in human fetuses with meningomyelocele

被引：26

作者：

de Wit O.A. ^{[1
]}

den Dunnen W.F.A. ^{[2
]}

Sollie K.M. ^{[3
]}

Muñoz R.I. ^{[4
]}

Meiners L.C. ^{[5
]}

Brouwer O.F. ^{[1
]}

Rodríguez E.M. ^{[4
]}

Sival D.A. ^{[6
]}

机构：

[1] Department of Neurology, University Medical Center, University of Groningen, 9700 RB, Groningen

[2] Department of Pathology and Laboratory Medicine, University Medical Center, University of Groningen, 9700 RB, Groningen

[3] Department of Obstetrics and Gynecology, University Medical Center, University of Groningen, 9700 RB, Groningen

[4] Instituto de Anatomía, Histologíca y Patología Facultad de Medicina, Universidad Austral de Chile, Valdivia

[5] Department of Radiology, University Medical Center, University of Groningen, 9700 RB, Groningen

[6] Department of Pediatrics, University Medical Center, University of Groningen, 9700 RB, Groningen

来源：

Cerebrospinal Fluid Research | / 5卷 / 1期

关键词：

Hydrocephalus; Ependymal Cell; Germinal Matrix; Cerebral Aqueduct; Denude Area;

D O I：

10.1186/1743-8454-5-4

中图分类号：

学科分类号：

摘要：

Background: Fetal spina bifida aperta (SBA) is characterized by a spinal meningomyelocele (MMC) and associated with cerebral pathology, such as hydrocephalus and Chiari II malformation. In various animal models, it has been suggested that a loss of ventricular lining (neuroepithelial/ ependymal denudation) may trigger cerebral pathology. In fetuses with MMC, little is known about neuroepithelial/ependymal denudation and the initiating pathological events. The objective of this study was to investigate whether neuroepithelial/ ependymal denudation occurs in human fetuses and neonates with MMC, and if so, whether it is associated with the onset of hydrocephalus. Methods: Seven fetuses and 1 neonate (16-40 week gestational age, GA) with MMC and 6 fetuses with normal cerebral development (22-41 week GA) were included in the study. Identification of fetal MMC and clinical surveillance of fetal head circumference and ventricular width was performed by ultrasound (US). After birth, MMC was confirmed by histology. We characterized hydrocephalus by increased head circumference in association with ventriculomegaly. The median time interval between fetal cerebral ultrasound and fixing tissue for histology was four days. Results: At 16 weeks GA, we observed neuroepithelial/ependymal denudation in the aqueduct and telencephalon together with sub-cortical heterotopias in absence of hydrocephalus and/or Chiari II malformation. At 21-34 weeks GA, we observed concurrence of aqueductal neuroepithelial/ ependymal denudation and progenitor cell loss with the Chiari II malformation, whereas hydrocephalus was absent. At 37-40 weeks GA, neuroepithelial/ependymal denudation coincided with Chiari II malformation and hydrocephalus. Sub-arachnoidal fibrosis at the convexity was absent in all fetuses but present in the neonate. Conclusion: In fetal SBA, neuroepithelial/ependymal denudation in the telencephalon and the aqueduct can occur before Chiari II malformation and/or hydrocephalus. Since denuded areas cannot re-establish cell function, neuro-developmental consequences could induce permanent cerebral pathology. © 2008 de Wit et al; licensee BioMed Central Ltd.

引用

共 41 条

[1]

Gilbert J.N., Jones K.L., Rorke L.B., Chernoff G.F., James H.E., Central nervous system anomalies associated with meningomyelocele, hydrocephalus, and the Arnold-Chiari malformation: Reappraisal of theories regarding the pathogenesis of posterior neural tube closure defects, Neurosurgery, 18, pp. 559-564, (1986)

[2]

Stein S.C., Schut L., Hydrocephalus in myelomeningocele, Childs Brain, 5, pp. 413-419, (1979)

[3]

Miyan J., Sobkowiak C., Draper C., Humanity lost: The cost of cortical maldevelopment. Is there light ahead?, Eur J Pediatr Surg, 11, SUPPL. 1, (2001)

[4]

Jimenez A.J., Tome M., Paez P., Wagner C., Rodriguez S., Fernandez-Llebrez P., Rodriguez E.M., Perez-Figares J.M., A programmed ependymal denudation precedes congenital hydrocephalus in the hyh mutant mouse, J Neuropathol Exp Neurol, 60, pp. 1105-1119, (2001)

[5]

Sarnat H.B., Role of human fetal ependyma, Pediatr Neurol, 8, pp. 163-178, (1992)

[6]

Sarnat H.B., Ependymal reactions to injury. A review, J Neuropathol Exp Neurol, 54, pp. 1-15, (1995)

[7]

Dominguez-Pinos M.D., Paez P., Jimenez A.J., Weil B., Arraez M.A., Perez-Figares J.M., Rodriguez E.M., Ependymal denudation and alterations of the subventricular zone occur in human fetuses with a moderate communicating hydrocephalus, J Neuropathol Exp Neurol, 64, pp. 595-604, (2005)

[8]

Bruner J.P., Tulipan N., Paschall R.L., Boehm F.H., Walsh W.F., Silva S.R., Hernanz-Schulman M., Lowe L.H., Reed G.W., Fetal surgery for myelomeningocele and the incidence of shunt-dependent hydrocephalus, JAMA, 282, pp. 1819-1825, (1999)

[9]

Paez P., Batiz L.F., Roales-Bujan R., Rodriguez-Perez L.M., Rodriguez S., Jimenez A.J., Rodriguez E.M., Perez-Figares J.M., Patterned neuropathologic events occurring in hyh congenital hydrocephalic mutant mice, J Neuropathol Exp Neurol, 66, pp. 1082-1092, (2007)

[10]

Wagner C., Batiz L.F., Rodriguez S., Jimenez A.J., Paez P., Tome M., Perez-Figares J.M., Rodriguez E.M., Cellular mechanisms involved in the stenosis and obliteration of the cerebral aqueduct of hyh mutant mice developing congenital hydrocephalus, J Neuropathol Exp Neurol, 62, pp. 1019-1040, (2003)

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