FGF-2 is required to prevent astrogliosis in the facial nucleus after facial nerve injury and mechanical stimulation of denervated vibrissal muscles  

作　　者：Arzu Hizay Mark Seitz Maria Grosheva Nektarios Sinis Yasemin Kaya Habib Bendella Levent Sarikcioglu Sarah A.Dunlop Doychin N.Angelov 

机构地区：[1]Department of Anatomy,Akdeniz University,Faculty of Medicine [2]Department of Anatomy I,University of Cologne [3]Department of Oto-Rhino-Laryngology,University Hospital Cologne [4]Depeartment of Plastic-,Hand-and Reconstructive Microsurgery [5]Department of Neurosurgery,Hospital Merheim,University of Witten-Herdecke [6]Experimental and Regenerative Neurosciences,School of Animal Biology,University of Western Australia(M092) 35 Stirling Highway

出　　处：《The Journal of Biomedical Research》2016年第2期142-148,共7页生物医学研究杂志（英文版）

基　　金：financially supported by the Koln Fortune Programm;the Jean-Uhrmacher Foundation;Akdeniz University Research Fund

摘　　要：Recently,we have shown that manual stimulation of paralyzed vibrissal muscles after facial-facial anastomosis reduced the poly-innervation of neuromuscular junctions and restored vibrissal whisking.Using gene knock outs,we found a differential dependence of manual stimulation effects on growth factors.Thus,insulin-like growth factor-1 and brain-derived neurotrophic factor are required to underpin manual stimulation-mediated improvements,whereas FGF-2 is not.The lack of dependence on FGF-2 in mediating these peripheral effects prompted us to look centrally,i.e.within the facial nucleus where increased astrogliosis after facial-facial anastomosis follows ＂synaptic stripping＂.We measured the intensity of Cy3-fluorescence after immunostaining for glial fibrillary acidic protein（GFAP） as an indirect indicator of synaptic coverage of axotomized neurons in the facial nucleus of mice lacking FGF-2（FGF-2^（-/-） mice）.There was no difference in GFAP-Cy3-fluorescence（pixel number,gray value range17-103） between intact wildtype mice（2.12± 0.37×10~7） and their intact FGF-2^（-/-） counterparts（2.12±0.27×10~7） nor after facial-facial anastomosis ＋handling（wildtype：4.06±0.32×10~7;FGF-2^（-/-）：4.39±0.17×10~7）.However,after facial-facial anastomosis,GFAP-Cy3-fluorescence remained elevated in FGF-2^（-/-）-animals（4.54±0.12×10~7）,whereas manual otimulation reduced the intensity of GFAP-immunofluorescence in wild type mice to values that were not significantly different from intact mice（2.63±0.39×10）.We conclude that FGF-2 is not required to underpin the beneficial effects of manual stimulation at the neuro-muscular junction,but it is required to minimize astrogliosis in the brainstem and,by implication,restore synaptic coverage of recovering facial motoneurons.Recently,we have shown that manual stimulation of paralyzed vibrissal muscles after facial-facial anastomosis reduced the poly-innervation of neuromuscular junctions and restored vibrissal whisking.Using gene knock outs,we found a differential dependence of manual stimulation effects on growth factors.Thus,insulin-like growth factor-1 and brain-derived neurotrophic factor are required to underpin manual stimulation-mediated improvements,whereas FGF-2 is not.The lack of dependence on FGF-2 in mediating these peripheral effects prompted us to look centrally,i.e.within the facial nucleus where increased astrogliosis after facial-facial anastomosis follows ＂synaptic stripping＂.We measured the intensity of Cy3-fluorescence after immunostaining for glial fibrillary acidic protein（GFAP） as an indirect indicator of synaptic coverage of axotomized neurons in the facial nucleus of mice lacking FGF-2（FGF-2^（-/-） mice）.There was no difference in GFAP-Cy3-fluorescence（pixel number,gray value range17-103） between intact wildtype mice（2.12± 0.37×10~7） and their intact FGF-2^（-/-） counterparts（2.12±0.27×10~7） nor after facial-facial anastomosis ＋handling（wildtype：4.06±0.32×10~7;FGF-2^（-/-）：4.39±0.17×10~7）.However,after facial-facial anastomosis,GFAP-Cy3-fluorescence remained elevated in FGF-2^（-/-）-animals（4.54±0.12×10~7）,whereas manual otimulation reduced the intensity of GFAP-immunofluorescence in wild type mice to values that were not significantly different from intact mice（2.63±0.39×10）.We conclude that FGF-2 is not required to underpin the beneficial effects of manual stimulation at the neuro-muscular junction,but it is required to minimize astrogliosis in the brainstem and,by implication,restore synaptic coverage of recovering facial motoneurons.

关 键 词：FGF-2 facial nerve axotomy astrogliosis whisking function polyinnervation 

分 类 号：R651.3[医药卫生—外科学]