title: Comparison of trophic factors' expression between paralyzed and recovering muscles after facial nerve injury. A quantitative analysis in time course.
abstract: After peripheral nerve injury, recovery of motor performance negatively correlates with the poly-innervation of neuromuscular junctions (NMJ) due to excessive sprouting of the terminal Schwann cells. Denervated muscles produce short-range diffusible sprouting stimuli, of which some are neurotrophic factors. Based on recent data that vibrissal whisking is restored perfectly during facial nerve regeneration in blind rats from the Sprague Dawley (SD)/RCS strain, we compared the expression of brain derived neurotrophic factor (BDNF), fibroblast growth factor-2 (FGF2), insulin growth factors 1 and 2 (IGF1, IGF2) and nerve growth factor (NGF) between SD/RCS and SD-rats with normal vision but poor recovery of whisking function after facial nerve injury. To establish which trophic factors might be responsible for proper NMJ-reinnervation, the transected facial nerve was surgically repaired (facial-facial anastomosis, FFA) for subsequent analysis of mRNA and proteins expressed in the levator labii superioris muscle. A complicated time course of expression included (1) a late rise in BDNF protein that followed earlier elevated gene expression, (2) an early increase in FGF2 and IGF2 protein after 2 days with sustained gene expression, (3) reduced IGF1 protein at 28 days coincident with decline of raised mRNA levels to baseline, and (4) reduced NGF protein between 2 and 14 days with maintained gene expression found in blind rats but not the rats with normal vision. These findings suggest that recovery of motor function after peripheral nerve injury is due, at least in part, to a complex regulation of lesion-associated neurotrophic factors and cytokines in denervated muscles. The increase of FGF-2 protein and concomittant decrease of NGF (with no significant changes in BDNF or IGF levels) during the first week following FFA in SD/RCS blind rats possibly prevents the distal branching of regenerating axons resulting in reduced poly-innervation of motor endplates.
authors.affiliation: Department of Oto-Rhino-Laryngology, University of Cologne, Germany.
authors.forename: Maria
authors.initials: M
authors.lastname: Grosheva
authors.affiliation: Department of Anatomy I, University of Cologne, Germany.
authors.forename: Klaus
authors.initials: K
authors.lastname: Nohroudi
authors.affiliation: Department of Anatomy I, University of Cologne, Germany.
authors.forename: Alisa
authors.initials: A
authors.lastname: Schwarz
authors.affiliation: Department of Anatomy I, University of Cologne, Germany.
authors.forename: Svenja
authors.initials: S
authors.lastname: Rink
authors.affiliation: Department of Neurosurgery, Hospital Merheim, University of Witten-Herdecke, Cologne, Germany.
authors.forename: Habib
authors.initials: H
authors.lastname: Bendella
authors.affiliation: Department of Anatomy, Akdeniz University, Antalya, Turkey.
authors.forename: Levent
authors.initials: L
authors.lastname: Sarikcioglu
authors.affiliation: Division of Neuroanatomy Innsbruck Medical University, 6020 Innsbruck, Austria.
authors.forename: Lars
authors.initials: L
authors.lastname: Klimaschewski
authors.affiliation: Department of Surgery,The Hospital for Sick Children, Toronto, Ontario M5G 1X8, Canada.
authors.forename: Tessa
authors.initials: T
authors.lastname: Gordon
authors.affiliation: Department of Anatomy I, University of Cologne, Germany. Electronic address: angelov.anatomie@uni-koeln.de.
authors.forename: Doychin N
authors.initials: DN
authors.lastname: Angelov
mesh_terms: D000818:Animals; D001522:Behavior, Animal; D019208:Brain-Derived Neurotrophic Factor / Q000096:biosynthesis / Q000235:genetics; D005152:Facial Muscles / Q000294:innervation / Q000378:metabolism* / Q000473:pathology*; D020220:Facial Nerve Injuries / Q000378:metabolism* / Q000473:pathology*; D005158:Facial Paralysis / Q000378:metabolism* / Q000473:pathology*; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000096:biosynthesis / Q000235:genetics; D007334:Insulin-Like Growth Factor I / Q000096:biosynthesis / Q000235:genetics; D007335:Insulin-Like Growth Factor II / Q000096:biosynthesis / Q000235:genetics; D020932:Nerve Growth Factor / Q000096:biosynthesis; D009414:Nerve Growth Factors / Q000096:biosynthesis* / Q000235:genetics; D009416:Nerve Regeneration; D009469:Neuromuscular Junction / Q000473:pathology; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function / Q000235:genetics; D014738:Vibrissae / Q000294:innervation
chemical_list: D019208:Brain-Derived Neurotrophic Factor; C000599313:Igf2 protein, rat; D009414:Nerve Growth Factors; D012333:RNA, Messenger; C548904:insulin-like growth factor-1, rat; D016222:Fibroblast Growth Factor 2; D007334:Insulin-Like Growth Factor I; D007335:Insulin-Like Growth Factor II; D020932:Nerve Growth Factor
keywords: Axotomy; BDNF; ELISA; FGF2; Functional recovery; IGF; Motoneuron; Motor endplates; NGF; Polyinnervation; RT-PCR; Vibrissae whisking