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ABSTRACT: Bone Morphogenetic Protein 4 (BMP4) is a member of the TGF-beta superfamily and is known to be important for the normal development of many tissues and organs, including the inner ear. Bmp4 homozygous null mice die as embryos, but Bmp4 heterozygous null (Bmp4(+/-)) mice are viable and some adults exhibit a circling phenotype, suggestive of an inner ear defect. To understand the role of BMP4 in inner ear development and function, we have begun to study C57BL/6 Bmp4(+/-) mice. Quantitative testing of the vestibulo-collic reflex, which helps maintain head stability, demonstrated that Bmp4(+/-) mice that exhibit circling behavior have a poor response in the yaw axis, consistent with semicircular canal dysfunction. Although the hair cells of the ampullae were grossly normal, the stereocilia were greatly reduced in number. Auditory brainstem responses showed that Bmp4(+/-) mice have elevated hearing thresholds and immunohistochemical staining demonstrated decreased numbers of neuronal processes in the organ of Corti. Thus Bmp4(+/-) mice have structural and functional deficits in the inner ear.
Hearing Research 04/2007; 225(1-2):71-9. · 2.70 Impact Factor
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ABSTRACT: The vestibulo-collic reflex (VCR) attempts to stabilize head position in space during motion of the body. Similar to the better-studied vestibulo-ocular reflex, the VCR is subserved by relatively direct, as well as indirect pathways linking vestibular nerve activity to cervical motor neurons. We measured the VCR using an electromagnetic technique often employed to measure eye movements; we attached a loop of wire (head coil) to an animal's head using an adhesive; then the animal was gently restrained with its head free to move within an electromagnetic field, and was subjected to sinusoidal (0.5-3 Hz) or abrupt angular acceleration (peak velocity approximately 200 degrees/s). Head rotation opposite in direction to body rotation was assumed to be driven by the VCR. To confirm that the compensatory head movements were in fact vestibular in origin, we plugged the horizontal canal unilaterally and then retested the animals 2, 8 and 15 days after the lesion. Two days after surgery, the putative VCR was almost absent in response to abrupt or sinusoidal rotations. Recovery commenced by day 8 and was nearly complete by day 15. We conclude that the compensatory head movements are vestibular in origin produced by the VCR. Similar to other species, there are robust compensatory mechanisms that restore the VCR following peripheral lesions.
Experimental Brain Research 12/2005; 167(1):103-7. · 2.39 Impact Factor
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ABSTRACT: The protective effect of dexamethasone (DEX) against noise-induced trauma, as reflected in hair cell destruction and elevation in auditory brainstem response (ABR) sensitivity, was assessed in guinea pigs. The animals were administered DEX (1, 10, 100, and 1000 ng/ml) or artificial perilymph (AP) via a mini-osmotic pump directly into scala tympani and, on the fourth day after pump implantation, exposed to 120 dB SPL octave band noise, centered at 4 kHz, for 24 h. Animals receiving DEX demonstrated a dose-dependent reduction in noise-induced outer hair cell loss (significant at 1, 10 and 100 ng/ml DEX animals compared to AP control animals) and a similar attenuation of the noise-induced ABR threshold shifts, observed 7 days following exposure (significant at 100 ng/ml DEX animals compared to AP control animals). These physiological and morphological results indicate that direct infusion of DEX into the perilymphatic space has protective effects against noise-induced trauma in the guinea pig cochlea.
Hearing Research 11/2004; 196(1-2):58-68. · 2.70 Impact Factor
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ABSTRACT: This study demonstrates the attenuation of aminoglycoside ototoxicity by cochlear infusion of dexamethasone (Dex) using a microcannulation-osmotic pump delivery system. The results indicate that treating the cochlea with Dex both before and after kanamycin administration was more effective in preventing ototoxicity than Dex treatment only after kanamycin administration. A concentration of 1 ng/ml Dex showed the greatest protective effect on both kanamycin-induced threshold shift of the auditory brainstem response and outer hair cell survival. These results show that the Dex treatment attenuates both functional and structural damage of the inner ear from aminoglycoside toxicity.
Hearing Research 06/2002; 167(1-2):61-70. · 2.70 Impact Factor
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ABSTRACT: Bone Morphogenetic Protein 4 (BMP4) is a member of the TGF-β superfamily and is known to be important for the normal development of many tissues and organs, including the inner ear. Bmp4 homozygous null mice die as embryos, but Bmp4 heterozygous null (Bmp4+/−) mice are viable and some adults exhibit a circling phenotype, suggestive of an inner ear defect. To understand the role of BMP4 in inner ear development and function, we have begun to study C57BL/6 Bmp4+/− mice. Quantitative testing of the vestibulo-collic reflex, which helps maintain head stability, demonstrated that Bmp4+/− mice that exhibit circling behavior have a poor response in the yaw axis, consistent with semicircular canal dysfunction. Although the hair cells of the ampullae were grossly normal, the stereocilia were greatly reduced in number. Auditory brainstem responses showed that Bmp4+/− mice have elevated hearing thresholds and immunohistochemical staining demonstrated decreased numbers of neuronal processes in the organ of Corti. Thus Bmp4+/− mice have structural and functional deficits in the inner ear.
Hearing Research.
