PMID- 18220258 OWN - NLM STAT- MEDLINE DCOM- 20080318 LR - 20220317 IS - 1096-9861 (Electronic) IS - 0021-9967 (Linking) VI - 507 IP - 4 DP - 2008 Apr 1 TI - Deafferentation-associated changes in afferent and efferent processes in the guinea pig cochlea and afferent regeneration with chronic intrascalar brain-derived neurotrophic factor and acidic fibroblast growth factor. PG - 1602-21 LID - 10.1002/cne.21619 [doi] AB - Deafferentation of the auditory nerve from loss of sensory cells is associated with degeneration of nerve fibers and spiral ganglion neurons (SGN). SGN survival following deafferentation can be enhanced by application of neurotrophic factors (NTF), and NTF can induce the regrowth of SGN peripheral processes. Cochlear prostheses could provide targets for regrowth of afferent peripheral processes, enhancing neural integration of the implant, decreasing stimulation thresholds, and increasing specificity of stimulation. The present study analyzed distribution of afferent and efferent nerve fibers following deafness in guinea pigs using specific markers (parvalbumin for afferents, synaptophysin for efferent fibers) and the effect of brain derived neurotrophic factor (BDNF) in combination with acidic fibroblast growth factor (aFGF). Immediate treatment following deafness was compared with 3-week-delayed NTF treatment. Histology of the cochlea with immunohistochemical techniques allowed quantitative analysis of neuron and axonal changes. Effects of NTF were assessed at the light and electron microscopic levels. Chronic BDNF/aFGF resulted in a significantly increased number of afferent peripheral processes in both immediate- and delayed-treatment groups. Outgrowth of afferent nerve fibers into the scala tympani were observed, and SGN densities were found to be higher than in normal hearing animals. These new SGN might have developed from endogenous progenitor/stem cells, recently reported in human and mouse cochlea, under these experimental conditions of deafferentation-induced stress and NTF treatment. NTF treatment provided no enhanced maintenance of efferent fibers, although some synaptophysin-positive fibers were detected at atypical sites, suggesting some sprouting of efferent fibers. CI - Copyright 2008 Wiley-Liss, Inc. FAU - Glueckert, Rudolf AU - Glueckert R AD - Department of Otolaryngology, Medical University of Innsbruck, A-6020 Innsbruck, Austria. FAU - Bitsche, Mario AU - Bitsche M FAU - Miller, Josef M AU - Miller JM FAU - Zhu, Yaying AU - Zhu Y FAU - Prieskorn, Diane M AU - Prieskorn DM FAU - Altschuler, Richard A AU - Altschuler RA FAU - Schrott-Fischer, Anneliese AU - Schrott-Fischer A LA - eng GR - P30 DC005188/DC/NIDCD NIH HHS/United States GR - R01 DC003820/DC/NIDCD NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't PL - United States TA - J Comp Neurol JT - The Journal of comparative neurology JID - 0406041 RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Enzyme Inhibitors) RN - 0 (Intercellular Signaling Peptides and Proteins) RN - 0 (Parvalbumins) RN - 0 (Protein Synthesis Inhibitors) RN - 0 (Synaptophysin) RN - 104781-85-3 (Fibroblast Growth Factor 1) RN - 59-01-8 (Kanamycin) RN - M5DP350VZV (Ethacrynic Acid) SB - IM MH - Animals MH - Auditory Pathways/drug effects/pathology MH - Brain-Derived Neurotrophic Factor/administration & dosage MH - Cochlea/*drug effects/pathology MH - Deafness/chemically induced/drug therapy/*pathology MH - Enzyme Inhibitors/toxicity MH - Ethacrynic Acid/toxicity MH - Female MH - Fibroblast Growth Factor 1/administration & dosage MH - Guinea Pigs MH - Image Processing, Computer-Assisted MH - Immunohistochemistry MH - Intercellular Signaling Peptides and Proteins/*administration & dosage MH - Kanamycin/toxicity MH - Male MH - Microscopy, Confocal MH - Microscopy, Electron, Transmission MH - Nerve Regeneration/*drug effects MH - Neurons/drug effects/pathology MH - Neurons, Afferent/drug effects/*pathology MH - Neurons, Efferent/drug effects/*pathology MH - Parvalbumins/metabolism MH - Protein Synthesis Inhibitors/toxicity MH - Synaptophysin/metabolism MH - Time EDAT- 2008/01/29 09:00 MHDA- 2008/03/19 09:00 CRDT- 2008/01/29 09:00 PHST- 2008/01/29 09:00 [pubmed] PHST- 2008/03/19 09:00 [medline] PHST- 2008/01/29 09:00 [entrez] AID - 10.1002/cne.21619 [doi] PST - ppublish SO - J Comp Neurol. 2008 Apr 1;507(4):1602-21. doi: 10.1002/cne.21619.