Article
New insights into cellular lesion mechanisms in the neural placode tissue of myelomeningoceles
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Authors
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Bea Kowitzke
- Klinik für Neurochirurgie, Universitätsklinikum Schleswig-Holstein, Campus Kiel, Germany
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Gesa Cohrs
- Klinik für Neurochirurgie, Universitätsklinikum Schleswig-Holstein, Campus Kiel, Germany
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Ivo Leuschner
- Institut für Pathologie, Sektion für Kinderpathologie, Universitätsklinikum Schleswig-Holstein, Campus Kiel, Germany
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Arend Koch
- Institut für Neuropathologie, Charité - Universitätsmedizin Berlin, Germany
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Janka Held-Feindt
- Klinik für Neurochirurgie, Universitätsklinikum Schleswig-Holstein, Campus Kiel, Germany
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Friederike Knerlich-Lukoschus
- Klinik für Neurochirurgie, Universitätsklinikum Schleswig-Holstein, Campus Kiel, Germany
| Published: | June 8, 2016 |
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Outline
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Objective: Myelomeningocele (MMC) repair has to address both, the deficient neurulation and external damaging mechanisms. The latter probably induce secondary lesion cascades subsequently impairing functionality of neuroepithelial tissue. Our aim was to identify specific mediators of these lesion cascades.
Method: The local ethical committee approved this study. Specimens obtained from MMC-repair surgeries performed within 72h after birth were screened for sufficient neuroepithelial tissue. Thus 16 cases were included. Respective clinical data for each case were collected. Controls included normal adult and fetal spinal cord specimens. Sections were immunostained with neuroglial, neural crest, mesenchymal and epithelial marker antibodies (GFAP, neurofilament (NF200kD), NeuN, synaptophysin, smooth muscle actin, melanocytes (HMB45), epithelial membrane antigen (EMA) and Vimentin). CD3 was used as inflammatory marker. Spatial distributions were analyzed and scored semiquantitatively. Immunohistochemistry for Interleukin-1beta (IL-1β), its receptor IL-1R1, erythropoietin (EPO), and EPOR was performed and analyzed qualitatively and semiquantitatively (ImageJ 1.43u, NIH, USA). Cellular localization of cytokine expression was confirmed via double-fluorescence-immuno-labeling with respective cellular markers. Further, Hypoxia Inducible Factor (HIF) 1 and 2 were investigated in the context of EPO expression.
Results: GFAP was expressed on high level while neuronal markers depicted neuronal cells and processes in respective placode areas. Selective cases exhibited inflammatory reaction with significant CD3-immunreactivity (IR). EMA and HMB45 were not expressed in the placodes. IL-1R and IL-1β IR-density were significantly elevated in all cases (p<0.001 vs. control). Their IR was co-expressed with NeuN, GFAP, and partially microglial markers. Neuronal EPOR IR was found in most placode tissue with significant elevated density level in 8 cases (3 cases p<0,01, 5 cases p<0,001, vs. control). EPO IR-density was significantly elevated in 40% of the cases (2 cases p <0,05, 2 cases p<0,01, 3 cases p<0,001 vs. control). HIF-2a IR was induced significantly in all cases (p<0,001 vs. control).
Conclusions: Our findings suggest that secondary lesion cascades take place in MMC placodes. We further identified inflammatory cytokines as potential mediators. The detection of neuronal EPOR in the placode provides a target for neuroprotective strategies.
