PMID- 18692557 OWN - NLM STAT- MEDLINE DCOM- 20081204 LR - 20131121 IS - 0378-5955 (Print) IS - 0378-5955 (Linking) VI - 244 IP - 1-2 DP - 2008 Oct TI - Morphological changes in spiral ganglion cells after intracochlear application of brain-derived neurotrophic factor in deafened guinea pigs. PG - 25-34 LID - 10.1016/j.heares.2008.07.004 [doi] AB - When guinea pigs are deafened with ototoxic drugs spiral ganglion cells (SGCs) degenerate progressively. Application of neurotrophins can prevent this process. Morphological changes of rescued SGCs have not been quantitatively determined yet. It might be that SGCs treated with neurotrophins are more vulnerable than SGCs in cochleae of normal-hearing guinea pigs. Therefore, the mitochondria and myelinisation of type-I SGCs were studied and the perikaryal area, cell circularity and electron density were determined. Guinea pigs were deafened with a subcutaneous injection of kanamycin followed by intravenous infusion of furosemide. Brain-derived neurotrophic factor (BDNF) delivery was started two weeks after the deafening procedure and continued for four weeks. Four cohorts of cochleae were studied: (1) cochleae of normal-hearing guinea pigs; (2) of guinea pigs two weeks after deafening; (3) six weeks after deafening; (4) cochleae treated with BDNF after deafening. The deafening procedure resulted in a progressive loss of SGCs. Six weeks after deafening the size of mitochondria, perikaryal area and cell circularity of the remaining untreated SGCs were decreased and the number of layers of the myelin sheath was reduced. In the basal part of the cochlea BDNF treatment rescued SGCs from degeneration. SGCs treated with BDNF were larger than SGCs in normal-hearing guinea pigs, whereas circularity had normal values and electron density was unchanged. The number of layers in the myelin sheath of BDNF-treated SGCs was reduced as compared to the number of layers in the myelin sheath of SGCs in normal-hearing guinea pigs. The morphological changes of SGCs might be related to the rapid loss of SGCs that has been reported to occur after cessation of BDNF treatment. FAU - Agterberg, Martijn J H AU - Agterberg MJ AD - Department of Otorhinolaryngology, Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht, Room G.02.531, P.O. Box 85500, 3508 GA Utrecht, The Netherlands. m.j.h.agterberg@umcutrecht.nl FAU - Versnel, Huib AU - Versnel H FAU - de Groot, John C M J AU - de Groot JC FAU - Smoorenburg, Guido F AU - Smoorenburg GF FAU - Albers, Frans W J AU - Albers FW FAU - Klis, Sjaak F L AU - Klis SF LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20080725 PL - Netherlands TA - Hear Res JT - Hearing research JID - 7900445 RN - 0 (Brain-Derived Neurotrophic Factor) RN - 59-01-8 (Kanamycin) RN - 7LXU5N7ZO5 (Furosemide) SB - IM MH - Animals MH - Brain-Derived Neurotrophic Factor/*metabolism MH - Cochlea/metabolism MH - Electrons MH - Female MH - Furosemide/pharmacology MH - Guinea Pigs MH - Kanamycin/pharmacology MH - Microscopy, Electron MH - Mitochondria/metabolism MH - Myelin Sheath/metabolism MH - Neurons/metabolism MH - Spiral Ganglion/*pathology EDAT- 2008/08/12 09:00 MHDA- 2008/12/17 09:00 CRDT- 2008/08/12 09:00 PHST- 2007/12/22 00:00 [received] PHST- 2008/07/01 00:00 [revised] PHST- 2008/07/02 00:00 [accepted] PHST- 2008/08/12 09:00 [pubmed] PHST- 2008/12/17 09:00 [medline] PHST- 2008/08/12 09:00 [entrez] AID - S0378-5955(08)00134-2 [pii] AID - 10.1016/j.heares.2008.07.004 [doi] PST - ppublish SO - Hear Res. 2008 Oct;244(1-2):25-34. doi: 10.1016/j.heares.2008.07.004. Epub 2008 Jul 25.