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Role of the subcommissural organ in the pathogenesis of congenital hydrocephalus in the HTx rat

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Abstract

The present investigation was designed to clarify the role of the subcommissural organ (SCO) in the pathogenesis of hydrocephalus occurring in the HTx rat. The brains of non-affected and hydrocephalic HTx rats from embryonic day 15 (E15) to postnatal day 10 (PN10) were processed for electron microscopy, lectin binding and immunocytochemistry by using a series of antibodies. Cerebrospinal fluid (CSF) samples of non-affected and hydrocephalic HTx rats were collected at PN1, PN7 and PN30 and analysed by one- and two-dimensional electrophoresis, immunoblotting and nanoLC-ESI-MS/MS. A distinct malformation of the SCO is present as early as E15. Since stenosis of the Sylvius aqueduct (SA) occurs at E18 and dilation of the lateral ventricles starts at E19, the malformation of the SCO clearly precedes the onset of hydrocephalus. In the affected rats, the cephalic and caudal thirds of the SCO showed high secretory activity with all methods used, whereas the middle third showed no signs of secretion. At E18, the middle non-secretory third of the SCO progressively fused with the ventral wall of SA, resulting in marked aqueduct stenosis and severe hydrocephalus. The abnormal development of the SCO resulted in the permanent absence of Reissner’s fibre (RF) and led to changes in the protein composition of the CSF. Since the SCO is the source of a large mass of sialilated glycoproteins that form the RF and of those that remain CSF-soluble, we hypothesize that the absence of this large mass of negatively charged molecules from the SA domain results in SA stenosis and impairs the bulk flow of CSF through the aqueduct.

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Acknowledgments

The authors acknowledge the valuable technical support of Mr. Genaro Alvial. The monoclonal antibody against nestin was obtained from the Developmental Studies Hybridoma Bank developed under the auspices of the NICHD and maintained by The University of Iowa, Department of Biological Sciences, Iowa City, IA 52242.

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Authors and Affiliations

  1. Instituto de Anatomía, Histología y Patología, Facultad de Medicina, Universidad Austral de Chile, Valdivia, Chile

    Alexander R. Ortloff, Karin Vío, Montserrat Guerra, Katherine Jaramillo & Esteban Rodríguez

  2. Escuela de Medicina Veterinaria, Universidad Católica de Temuco, Temuco, Chile

    Alexander R. Ortloff

  3. Institute of Experimental Internal Medicine, Otto-von-Guericke University Magdeburg, Leipziger Strasse 44-0, 39120, Magdeburg, Germany

    Thilo Kaehne

  4. Gagle Brook House, Chesterton, Bicester, OX 1UF, UK

    Hazel Jones

  5. Division of Pediatric Neurosurgery, Department of Neurosurgery, Medical School, University of Utah, Salt Lake City, UT 84132, USA

    James P. McAllister II

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  1. Alexander R. Ortloff
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  2. Karin Vío
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  3. Montserrat Guerra
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  4. Katherine Jaramillo
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  5. Thilo Kaehne
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  7. James P. McAllister II
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  8. Esteban Rodríguez
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Correspondence to Esteban Rodríguez.

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A.R. Ortloff and K. Vío should be considered as first authors.

This work was supported by grants from Fondecyt (Chile) to E. Rodríguez (nos. 1070241 and 1111018), a Hydrocephalus Association Established Investigator Award to E. Rodríguez and J.P. McAllister (no. 51002705), a grant from Universidad Austral de Chile/DID S-2006-72 to K. Vío and a Conicyt PhD Fellowship to A.R. Ortloff.

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Ortloff, A.R., Vío, K., Guerra, M. et al. Role of the subcommissural organ in the pathogenesis of congenital hydrocephalus in the HTx rat. Cell Tissue Res 352, 707–725 (2013). https://doi.org/10.1007/s00441-013-1615-9

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