Rescue strategies by the topical application of TGFbeta3 and GDF5 to prevent a craniosynostosis in M. Crouzon mice and spatial evaluation of the gene expression pattern in the cranial vault and the dura mater of M. Crouzon mice.

点击翻译按钮获取中文摘要

Craniosynostoses are characterized by premature closure of cranial sutures. These occur as part of syndromes with Fibroblast Growth Factor Receptor 2 (FGFR2) mutations, e.g. the Apert syndrome and M. Crouzon, or occur sporadically. The natural growth of the brain is, however, affected and thus leads to an increase in intracranial pressure with the consequence of neuronal damage. Then, a surgical separation of these synostotic sutures is necessary. A postoperative recurrence of craniosynostosis happens, however, in 20% and demands a further surgical intervention. This work has the objective to evaluate new therapeutic approaches to prevent the recurrence of craniosynostoses postoperatively in mice suffering from M. Crouzon. In healthy rats TGFbeta3 has already been used successfully. We as well will apply TGFbeta3 and GDF5 locally to prevent a recurrence of craniosynostoses in M. Crouzon postoperatively. Several experimenal groups are established to differentiate the influence of surgery, scaffold (Collagen) and growth factors on the recurrence of craniosynostosis in M.Crouzon and wild type mice. The success of the local applications are evaluated by sonographic and x-ray examinations as well as histomorphologic and immunohistologic methods. In addition to the examination of histological parameters, the sutures will be also examined immunohistochemically. In contrast to previously published studies, the sutures of the viscerocranium will also be included in the analysis. In another series of experiments the influence of the dura mater on the cranial sutures will be examined, because is has a paracrine impact on the development of craniosynostoses. With the help of a topographic, 3D visualization of the protein expression of the dura mater and of the bone, wild-type mice and M.Crouzon mice will be compared in order to investigate spatial mismatches of sutures and dura mater. This proof could also have therapeutic implications.