Volume 12 Supplement 1

Abstracts from Hydrocephalus 2015

Open Access

Decorin reduces white matter pathology in experimental hydrocephalus: a diffusion tensor imaging and immunohistochemical study

  • James Patterson McAllister1, 3Email author,
  • Anuriti Aojula2,
  • Hannah Botfield2,
  • Osama Abdullah3,
  • Ana Maria Gonzalez2,
  • Dustin Ragan1,
  • Ann Logan2 and
  • Alexandra Sinclair2
Fluids and Barriers of the CNS201512(Suppl 1):O59

https://doi.org/10.1186/2045-8118-12-S1-O59

Published: 18 September 2015

Introduction

We have shown previously that Decorin, by antagonizing TGF-β–mediated subarachnoid fibrosis, prevents ventriculomegaly in experimental juvenile hydrocephalus. To focus on white matter alterations, we sought to correlate cytopathological changes induced by hydrocephalus with diffusion tensor imaging (DTI) parameters and determine if Decorin could prevent these changes.

Methods

Communicating hydrocephalus was induced in 3-week-old rats with basal cistern injections of kaolin; age-matched controls were intact (n=4) and kaolin-no treatment (n=4) animals. Immediately following kaolin injections, animals received a 14-day continuous intraventricular infusion of phosphate-buffered saline (n=6) or human recombinant Decorin (n=5) via osmotic minipumps. At 14 days post-kaolin, all rats underwent MRI/DTI scanning followed immediately by sacrifice and brain fixation. DTI voxel-based analysis was performed on 4 serial rostral-to-caudal slices to quantify mean fractional anisotropy (FA), diffusivity (MD), axial diffusivity (AD) and radial diffusivity (RD) of the corpus callosum (CC) and periventricular white matter (PVWM). Immunohistochemistry and stereology were employed to quantify astrogliosis (GFAP) and aquaporin-4 (AQP4) levels in the CC and PVWM at caudal levels.

Results

Compared to intact animals (rostral 1.3±0.1 and caudal 0.9±0.1 ventricular volume), the caudal lateral ventricles were significantly larger in kaolin-only (16.2±2.8, p=0.005) and kaolin-PBS (21.0±5.4,p<0.001) animals than rostral portions (8.0±1.7 and 10.1±3.8, respectively). Following this gradient, untreated hydrocephalic rats exhibited significantly (p<0.01) decreased FA and increased RD in the caudal-most CC and increased MD and AD in the caudal PVWM compared to intact controls. Decorin significantly (p<0.05) reversed the RD and MD changes in the caudal CC and PVWM MD (p<0.05). Such DTI reversals were not discovered in the rostral CC and PVWM. A significant increase in GFAP immunostaining resulted in a positive correlation (p<0.05) between CC GFAP levels and the caudal-most CC RD. In the caudal PVWM, MD and AQP4 levels and AD and GFAP presence were positively correlated (p<0.01).

Conclusions

These results indicate that regional differences exist in ventricular and DTI parameters, and that Decorin has the therapeutic potential to decrease microstructural damage in juvenile hydrocephalus.

Authors’ Affiliations

(1)
Neurosurgery, Washington University School of Medicine
(2)
Neurotrauma and Neurodegeneration, School of Clinical and Experimental Medicine, University of Birmingham
(3)
Bioengineering, University of Utah

References

  1. Botfield Hannah, Gonzalez Maria Ana, Abdullah Osama, Skjolding Anders, Berry Martin, McAllister James, Logan Ann: Decorin prevents the development of juvenile communicating hydrocephalus. Brain. 2013, 136: 2842-2858. 10.1093/brain/awt203.View ArticlePubMedGoogle Scholar
  2. McAllister James, Michael Williams, Walker Marion, Kestle John, Relkin Norman, Anderson Amy, Gross Paul, Browd Samuel: An update on research priorities in hydrocephalus: overview of the third National Institutes of Health–sponsored symposium “Opportunities for Hydrocephalus Research: Pathways to Better Outcomes”. J Neurosurg. 2015,Google Scholar
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Copyright

© McAllister et al. 2015

This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

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