Minocycline attenuates gentamicin induced hair cell loss in neonatal cochlear cultures

Corbacella, Elisa; Lanzoni, Irene; Ding, Dalian; Previati, Maurizio; Salvi, Richard

doi:10.1016/j.heares.2004.03.012

Cited by 54 publications

(41 citation statements)

References 41 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…This expression has been observed in hair cells Ladrech et al, 2004;Mangiardi et al, 2004;Yang et al, 2004b;Hu et al, 2006), spiral ganglion cells (Ladrech et al, 2004;Labbe et al, 2005;Lang et al, 2005), stria vascularis and spiral ligament (Watanabe et al, 2003), and lateral wall (Labbe et al, 2005). Confirming an important role for caspase activation in the pathway to cell death, caspase inhibitors have been shown to prevent cell death in the inner ear after aminoglycoside treatment, chemotherapeutics, hypoxia, or NTF withdrawal (Cheng et al, 1999;Nakagawa et al, 2003;Zhang et al, 2003;Corbacella et al, 2004;Okuda et al, 2005;Wei et al, 2005).…”

Section: Caspase-dependent Cell Death: Extrinsic (Receptor-mediated) mentioning

confidence: 84%

Mechanisms of noise-induced hearing loss indicate multiple methods of prevention

et al. 2007

View full text Add to dashboard Cite

Recent research has shown the essential role of reduced blood flow and free radical formation in the cochlea in noise-induced hearing loss (NIHL). The amount, distribution, and time course of free radical formation have been defined, including a clinically significant late formation 7-10 days following noise exposure, and one mechanism underlying noise-induced reduction in cochlear blood flow has finally been identified. These new insights have led to the formulation of new hypotheses regarding the molecular mechanisms of NIHL; and, from these, we have identified interventions that prevent NIHL, even with treatment onset delayed up to 3 days post-noise. It is essential to now assess the additive effects of agents intervening at different points in the cell death pathway to optimize treatment efficacy. Finding safe and effective interventions that attenuate NIHL will provide a compelling scientific rationale to justify human trials to eliminate this single major cause of acquired hearing loss.

show abstract

Section: Caspase-dependent Cell Death: Extrinsic (Receptor-mediated) mentioning

confidence: 84%

Mechanisms of noise-induced hearing loss indicate multiple methods of prevention

et al. 2007

View full text Add to dashboard Cite

show abstract

“…Free radical formation has been implicated in all. Interventions can be directed at preventing initial ROS formation and maintaining cochlear blood flow (as reported here and by others); alternative therapeutic interventions and strategies include neurotrophic growth factors [119][120][121][122], steroids [123,124], calcineurin inhibitors [125,126], caspase inhibitors [127][128][129][130][131][132], and Src protein tyrosine kinase (Src-PTK) inhibitors [133]. Each of these are at least partially effective in prevention of hearing loss and hair cell death; none of these strategies have alone been sufficiently effective.…”

Section: Discussionmentioning

confidence: 94%

Free radical scavengers vitamins A, C, and E plus magnesium reduce noise trauma

Prell

Hughes

Miller

2007

Free Radical Biology and Medicine

198

188

View full text Add to dashboard Cite

Free radical formation in the cochlea plays a key role in the development of noise-induced hearing loss (NIHL). The amount, distribution, and time course of free radical formation have been defined, including a clinically significant formation of both reactive oxygen species and reactive nitrogen species 7-10 days following noise exposure. Reduction in cochlear blood flow as a result of free radical formation has also been described. Here we report that the antioxidant agents, vitamins A, C, and E, act in synergy with magnesium to effectively prevent noise-induced trauma. Neither the antioxidant agents nor magnesium reliably reduced NIHL or sensory cell death with the doses we used when these agents were delivered alone. In combination, however, they were highly effective in reducing both hearing loss and cell death even with treatment initiated just one hour prior to noise exposure. This study supports roles for both free radical formation and noise-induced vasoconstriction in the onset and progression of NIHL. Identification of this safe and effective antioxidant intervention that attenuates NIHL provides a compelling rationale for human trials in which free radical scavengers are used to eliminate this single major cause of acquired hearing loss. Keywords cochlea; free radical; noise; hearing; antioxidant; vasodilation Mechanical destruction of cells in the organ of Corti was once assumed to be the primary cause of noise-induced hearing loss (NIHL) [1][2][3][4][5][6][7][8], with perhaps some effect of reduced blood flow to the inner ear [9][10][11][12][13][14][15][16][17][18]. We now know that another key factor is intense metabolic activity that results in production of excess free radicals [19][20][21][22][23] and lipid peroxidation products [24]. Noise-induced production of reactive oxygen species (ROS) in the cochlea has now been well characterized, and several recent reviews are available [25][26][27]. Mitochodrial dysfunction and ROS production have been implicated in numerous neurodegenerative syndromes and diseases [28-34, see 35,36]. The use of antioxidant agents holds significant therapeutic promise for many neurodegenerative processes [32,33,[37][38][39][40][41][42], and there is some suggestion that Correspondence to: C. G. Le Prell, Kresge Hearing Research Institute, University of Michigan, 1301 East Ann Street, Ann Arbor, MI 48109-0506, USA. Tel: +1-734-763-5104; fax +1-734-764-0014. E-mail address: colleeng@umich.edu. Disclosure. Dr. Miller is a founding member and Chairman of the Board of Directors at OtoMedicine, Inc., a company that has an option to license the intellectual property described in this report. Dr. Le Prell is a paid consultant to OtoMedicine, Inc. Drs. Miller and Le Prell have disclosed these relationships to the Medical School Conflict of Interest Board at the University of Michigan; conflict management plans including semi-annual review by the Board are in place.Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publicatio...

show abstract

“…Our procedures for preparing cochlear organotypic cultures have been described in detail in earlier publications (Corbacella et al, 2004;Ding et al, 2002;Ding et al, 2007;Lanzoni et al, 2005). Rat pups (CDF (F344), Charles River Laboratory Inc.) were decapitated on postnatal day 2−3.…”

Section: Cochlear Organotypic Culturesmentioning

confidence: 99%

“…Hair cells were evaluated along the entire length of the cochlea from apex to base. The stereocilia bundles, which are heavily labeled with Alexa 488-phalloidin, were clearly visible allowing for easy identification of hair cells that were present or missing (Corbacella et al, 2004). Hair cells were counted as missing if the stereocilia were missing and the cuticular plate was damage.…”

Section: Histologymentioning

confidence: 99%

Cytotoxic effects of dimethyl sulphoxide (DMSO) on cochlear organotypic cultures

2008

Self Cite

View full text Add to dashboard Cite

The amphipathic molecule dimethyl sulphoxide (DMSO) is a solvent often used to dissolve compounds applied to the inner ear; however, little is known about its potential cytotoxic side effects. To address this question, we applied 0.1 to 6% DMSO for 24 h to cochlear organotypic cultures from postnatal day 3 rats and examined its cytotoxic effects. DMSO concentrations of 0.1% and 0.25% caused little or no damage. However, concentrations between 0.5 and 6% resulted in stereocilia damage, hair cell swelling and a dose-dependent loss of hair cells. Hair cell damage began in the basal turn of the cochlea and spread towards the apex with increasing concentration. Surprisingly, DMSO-induced damage was greater for inner hair cells than outer hair cell whereas nearby supporting cells were largely unaffected. Most hair cell death was associated with nuclear shrinkage and fragmentation, morphological features consistent with apoptosis. DMSO treatment induced TUNEL positive staining in many hair cells and activated both initiator caspase-9 and caspase-8 and executioner caspase-3; this suggests that apoptosis is initiated by both intrinsic mitochondrial and extrinsic membrane cell death signaling pathways.

show abstract

Minocycline attenuates gentamicin induced hair cell loss in neonatal cochlear cultures

Cited by 54 publications

References 41 publications

Mechanisms of noise-induced hearing loss indicate multiple methods of prevention

Mechanisms of noise-induced hearing loss indicate multiple methods of prevention

Free radical scavengers vitamins A, C, and E plus magnesium reduce noise trauma

Cytotoxic effects of dimethyl sulphoxide (DMSO) on cochlear organotypic cultures

Contact Info

Product

Resources

About