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.

颅缝早闭的特征是颅缝过早闭合。这些作为具有成纤维细胞生长因子受体2（FGFR 2）突变的综合征的一部分发生，例如Apert综合征和M. Crouzon，或偶尔发生。然而，大脑的自然生长受到影响，从而导致颅内压增加，结果是神经元损伤。然后，手术分离这些骨性结合缝是必要的。术后复发的颅缝早闭发生，然而，在20%，需要进一步的手术干预。 这项工作的目的是评估新的治疗方法，以防止复发的颅缝早闭术后小鼠患有M。克鲁松在健康的大鼠中，TGF β 3已经被成功应用。我们也将局部应用TGF β 3和GDF 5来预防M的颅缝早闭复发。术后Crouzon。建立几个实验组以区分手术、支架（胶原）和生长因子对M.Crouzon和野生型小鼠中颅缝早闭复发的影响。局部应用的成功通过超声和X线检查以及组织形态学和免疫组织学方法进行评估。除组织学参数检查外，还将对缝线进行化学染色检查。与之前发表的研究不同，分析中还将纳入脏颅缝线。在另一系列实验中，将检查硬脑膜对颅缝的影响，因为它对颅缝早闭的发展有旁分泌影响。借助于硬脑膜和骨的蛋白质表达的地形图、3D可视化，将比较野生型小鼠和M.Crouzon小鼠，以研究缝线和硬脑膜的空间错配。这一证据也可能具有治疗意义。

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.