title: Ectopic Muscle Expression of Neurotrophic Factors Improves Recovery After Nerve Injury.
abstract: Sciatic nerve damage is a common medical problem. The main causes include direct trauma, prolonged external nerve compression, and pressure from disk herniation. Possible complications include leg numbness and the loss of motor control. In mild cases, conservative treatment is feasible. However, following severe injury, recovery may not be possible. Neuronal regeneration, survival, and maintenance can be achieved by neurotrophic factors (NTFs). In this study, we examined the potency of combining brain-derived neurotrophic factor (BDNF), glial-derived neurotrophic factor (GDNF), vascular endothelial growth factor (VEGF), and insulin-like growth factor-1 (IGF-1) on the recovery of motor neuron function after crush injury of the sciatic nerve. We show that combined NTF application increases the survival of motor neurons exposed to a hypoxic environment. The ectopic expression of NTFs in the injured muscle improves the recovery of the sciatic nerve after crush injury. A significantly faster recovery of compound muscle action potential (CMAP) amplitude and conduction velocity is observed after muscle injections of viral vectors expressing a mixture of the four NTF genes. Our findings suggest a rationale for using genetic treatment with a combination of NTF-expressing vectors, as a potential therapeutic approach for severe peripheral nerve injury.
authors.affiliation: Sagol School of Neuroscience, Tel-Aviv University, Tel-Aviv, Israel.|Felsenstein Medical Research Center, Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel.
authors.forename: Micaela Johanna
authors.initials: MJ
authors.lastname: Glat
authors.affiliation: Department of Neurology, Rabin Medical Center, Petach Tikva, Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel.
authors.forename: Felix
authors.initials: F
authors.lastname: Benninger
authors.affiliation: Felsenstein Medical Research Center, Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel.
authors.forename: Yael
authors.initials: Y
authors.lastname: Barhum
authors.affiliation: Felsenstein Medical Research Center, Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel.
authors.forename: Tali
authors.initials: T
authors.lastname: Ben-Zur
authors.affiliation: Department of Neurology, Rabin Medical Center, Petach Tikva, Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel.
authors.forename: Elena
authors.initials: E
authors.lastname: Kogan
authors.affiliation: Department of Neurology, Rabin Medical Center, Petach Tikva, Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel.
authors.forename: Israel
authors.initials: I
authors.lastname: Steiner
authors.affiliation: Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel.
authors.forename: David
authors.initials: D
authors.lastname: Yaffe
authors.affiliation: Sagol School of Neuroscience, Tel-Aviv University, Tel-Aviv, Israel. danioffen@gmail.com.|Felsenstein Medical Research Center, Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel. danioffen@gmail.com.|The Neuroscience Laboratory, Felsenstein Medical Research Center, Rabin Medical Center, 49100, Petah Tikva, Israel. danioffen@gmail.com.
authors.forename: Daniel
authors.initials: D
authors.lastname: Offen
mesh_terms: D000200:Action Potentials; D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000494:pharmacology / Q000627:therapeutic use*; D002460:Cell Line; D015316:Genetic Therapy; D051100:Glial Cell Line-Derived Neurotrophic Factor / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology / Q000627:therapeutic use; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018482:Muscle, Skeletal / Q000378:metabolism* / Q000502:physiology; D009416:Nerve Regeneration / Q000187:drug effects; D059348:Peripheral Nerve Injuries / Q000188:drug therapy*; D020127:Recovery of Function; D012584:Sciatic Nerve / Q000187:drug effects / Q000293:injuries / Q000502:physiology; D042461:Vascular Endothelial Growth Factor A / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D051100:Glial Cell Line-Derived Neurotrophic Factor; D042461:Vascular Endothelial Growth Factor A; D007334:Insulin-Like Growth Factor I
keywords: Compound muscle action potential (CMAP); Conduction velocity; Nerve injury; Neurotrophic factors