Mitochondrial role in hair cell survival after injury

Abstract

The role of mitochondrial biogenesis in hair cell survival after injury was evaluated by inhibiting mitochondrial protein synthesis with chloramphenicol and then studying the effects on hair cell survival after exposure to two different types of ototoxins, gentamicin and acoustic trauma. Seven- to 10-day-old chicks were treated with either a single injection of gentamicin (250 mg/kg) or noise (1500 Hz at 120 dB sound pressure level for 14 hours). A subset of the gentamicin- and noise-treated animals also received chloramphenicol (1200 mg/kg during a 24-hour period) through a subcutaneous osmotic pump. A control group received chloramphenicol alone (1200 mg/kg during a 24-hour period). All animals were sacrificed after 5 days, and their basilar papillae (cochleas) were prepared for scanning electron microscopy. Hair cell loss was quantified with stereologic techniques. Animals treated with chloramphenicol alone did not have any evidence of hair cell loss. Gentamicin-treated animals had characteristic hair cell loss beginning at the basal tip and tapering out along the inferior edge more distally. The addition of chloramphenicol to gentamicin treatment significantly increased hair cell loss by 30%, extending the area of hair cell loss into the superior hair cell region at the distal boundary of the lesion. Pure-tone noise exposure characteristically produced hair cell loss along the inferior edge and occasionally included hair cells along the most superior edge. Addition of chloramphenicol to noise exposure significantly increased hair cell loss by 80%, with extension of the lesion across the full width of the sensory epithelium and basally. These results demonstrate that mitochondrial biogenesis is involved in cellular responses to injury. They suggest that mitochondrial function may regulate the probability of survival after metabolic challenges to hair cell integrity.

Effects of hyperbaric oxygen treatment on auditory hair cells after acute noise damage

“…However, even though there was no full reversibility, the significant difference in the signalto-noise ratio of the DPOAE amplitude in G3 after exposure to noise and after HOT (p = 0.0159) indicates greater recovery in G3 compared with G2, that could be attributed to the therapeutic method used. Mitochondrial biogenesis is involved in the cell response to injury, possibly regulating the probability of cell survival after metabolic challenges to hair cell integrity [11]. Restored ionic equilibrium helps damaged hair cells to survive the interval of lack of oxygen perilymph supply.…”

“…Experimental studies on animals have demonstrated that AAT due to cochlear exposure to intense noise provokes structural changes in the OHC of the cochlea, initially compromising those located in the first row (R1) and later in the second (R2) and third (R3) rows progreding to inner and OHC involvement [3,8,26], with large part of the injuries being located in the basal turn [11,13].…”

“…AAT results in structural changes such as the rupture of cell membranes, which reduces cochlear blood flow and causes destruction of cochlear hair cells and/or dendrites of primary auditory neurons [3,[7][8][9]13]. Mitochondrial biogenesis is involved in the cell response to injury and can regulate the probability of cell survival after metabolic challenges to hair cell integrity [11]. The reduction of cochlear blood flow causes a reduction of oxygen in the fluids of the inner ear, reducing the various cell activities depending on blood flow [13].…”

Pharmacological rescue of noise induced hearing loss using N-acetylcysteine and acetyl-l-carnitine

“…The injured mitochondria in turn produce relatively more ROS further accentuating the damage (Lenaz et al, 1998;Poderoso et al, 2000). Mitochondrial injury is a critical factor in NIHL resulting from excessive ROS generation within mitochondria or from glutamate excitotoxicity or GSH depletion (Hyde and Rubel, 1995;Kroemer, 1999;Kroemer and Reed, 2000;Kopke et al, 2002;Coling et al, 2003;Fischel-Ghodsian et al, 2004). It is suggested that ALCAR protect mitochondria from oxidative stress by maintaining normal electron transport and reducing ROS production by way of its effects on the mitochondrial membrane.…”

Ocsyn and mitochondrial–canalicular complexes in vestibular hair cells

“…In neurons, mitochondria play an important role in calcium homeostasis by sequestering cytosolic calcium loads (Werth and Thayer, 1994;Budd and Nicholls, 1996;Gunter et al, 2000). In hair cells, mitochondria are involved in calcium regulation (Kennedy, 2002) and hair cell survival after injury (Hyde and Rubel, 1995).…”