PubMed Health⌕ Search

Biomedical subjects

D A Cotanche

Publications and source records attributed to D A Cotanche.

47 records · Page 3Linked to original sources
PubMed1987

Regeneration of the tectorial membrane in the chick cochlea following severe acoustic trauma.

Damage to the tectorial membrane caused by acoustic trauma was examined with scanning and transmission electron microscopy immediately after exposure and at selected time points over a 10 day recovery period. At 0 h of recovery the structure of the tectorial membrane overlying the region of hair cell damage was severely disrupted and connections between the membrane and the basilar papilla were lost. By 24 h of recovery, regeneration of the tectorial membrane was evident in the secretion of new matrix materials by the supporting cells of the basilar papilla. By 10 days of recovery a new honeycomb-like matrix had replaced the segment of damaged tectorial membrane, re-established connections with hair cell stereocilia and become fused with adjacent regions of undamaged tectorial membrane. However, the regenerated segment included only the honeycomb-like structure of the lower layer of the normal tectorial membrane. The laterally-oriented fibers which form the upper layer of the membrane were not regenerated over the damaged region. These findings indicate that the tectorial membrane is regenerated in parallel with the hair cells during recovery from acoustic trauma but the full extent of this recovery and its effect on cochlear function are not yet clear.

Animals↗
PubMed1987

Development of hair cell stereocilia in the avian cochlea.

The establishment of an embryonic hair cell's stereociliary bundle involves the coordinated regulation of several morphogenetic events. The developing hair cell organizes the assembly of individual stereocilia, regulates the growth of the stereociliary bundle, and aligns the orientation of the bundle. During development, individual stereocilia exhibit three phases of growth: (1) an initial assembly and elongation of a small number of actin filaments; (2) the development of the stereocilia rootlet and the addition of more filaments to each stereocilium; (3) a second growth phase where elongation of the actin filaments resumes. These three phases involve different biochemical conditions for actin assembly and, thus, are temporally separated during development. Each hair cell also regulates the size of its stereociliary bundle so that it fits into the precise basal-to-apical gradient in stereocilia length and width seen in the mature cochlea. Orientation of the stereociliary bundles also changes during development. Very young hair cells exhibit a non-uniform orientation. Early in development, neighboring groups of cells rapidly acquire a uniform orientation. A more gradual shift in orientation continues throughout development, so that by maturity most of the hair cells are oriented toward the abneural edge of the sensory epithelium.

Animals↗
PubMed1987

Immunocytochemical and quantitative studies of Na+,K+-ATPase distribution in the developing chick cochlea.

Immunocytochemical methods were used to examine cryosections of the embryonic and neonatal chicken cochlea in order to study the histological distribution of the Na+,K+-ATPase molecule during maturation. In complementary studies the Na+,K+-ATPase capacity of microdissected freeze-dried substructures of the cochlea was determined fluorometrically. The dark cell of the tegmentum vasculosum exhibited intense immunochemical staining of the convoluted basolateral infoldings. The adjacent light cells demonstrated very little staining. The plasma membrane of the hair cell was also stained as were the first order auditory neurons, including the cell soma. The homogene cells and the supporting cells were unstained. The dark cell was only lightly stained with the antibody at stage 45 but became more intense and selective by the seventh postnatal day. The other cells of the cochlear duct exhibited specific immunofluorescent staining of their plasma membranes from stage 45 onwards and the fluorescent intensity did not change. The tegmentum vasculosum exhibited very high activities of the Na+,K+-ATPase enzyme relative to the other structures of the cochlea. Furthermore, a pronounced gradient of enzymatic activity was detected longitudinally. The proximal tip (or high-frequency end) had a sixteen-fold greater capacity for Na+- and K+-dependent ATP hydrolysis relative to the distal tip (or low-frequency end). The appearance of this enzyme in the tegmentum vasculosum during the development of the cochlea paralleled the known rate of improvement in hearing thresholds.

Animals↗
PubMed1985

Parameters of growth in the embryonic and neonatal chick basilar papilla.

The growth of the basilar papilla in the chick cochlear duct was studied utilizing light, scanning, and transmission electron microscopy. The ages of the cochleae investigated ranged from embryonic day 6 to post-hatching day 7. The changes in the length and width of the basilar papilla as well as the establishment of its spatula-like shape were correlated with the maturation of the hair cells' apical surfaces and the changes in the cellular organization of the sensory epithelium. The histological reorganization of the distal hair cell nuclei was concomitant with the broadening of the distal region of the basilar papilla and occurred at a later stage than the reorganization of the proximal hair cell nuclei. Since the stereociliary bundles on all the hair cells are differentiated quite early, it appears that the delayed reorganization of the distal nuclei is associated with anatomical constraints on the cochlear duct, rather than a later differentiation of the distal sensory epithelium. A clear understanding of how growth of the cochlear duct influences both the distribution of hair cells on the basilar papilla's surface and the cellular organization in the sensory epithelium is critical to future studies correlating ultrastructural development with functional maturation of the auditory system.

Animals↗
PubMed1984

The development of stereociliary bundles in the cochlear duct of chick embryos.

The differentiation of hair cell stereociliary bundles was investigated during early stages of embryonic development in the chick cochlear duct. The ultrastructural characteristics of the differentiating stereocilia and the position of the hair cells at the time of their differentiation were determined with scanning (SEM) and transmission (TEM) electron microscopy. Stereocilia were first identifiable with SEM as early as embryonic day 6 (stage 29) in only the distal region of the basilar papilla. By embryonic day 7.5 (stage 32) stereocilia were detected with both SEM and TEM on hair cells located in the distal two-thirds of the basilar papilla. Stereociliary bundles were recognizable throughout the entire basilar papilla by embryonic day 9 (stage 35). At this stage the hair cells exhibited a distal-to-proximal gradient in the cell surface area and the number of stereocilia on each hair cell. These results suggest that there is a distal-to-proximal wave of hair cell differentiation which occurs at a very early time period in the development of the chick cochlea. Both the timing and the direction of the stereociliary differentiation contrast with previous ultrastructural reports of avian hair cell development, yet compare favorably with the patterns of functional development in the auditory system.

Animals↗
PubMed1982

Scanning electron microscopy of the developing chick tegmentum vasculosum.

The developing tegmentum vasculosum in the chick cochlea was analyzed by means of scanning electron microscopy. Chick embryos representative of Hamilton and Hamburger stages 35, 37, 41 and 45 were examined in order to study the morphogenesis of the "lamellae" (Knowlton, 1967), or folds, of the tegmentum vasculosum and the differentiation of the light and dark cell luminal surfaces. At stage 35 low folds are distinguishable in the proximal segment of the cochlear duct only. In subsequent stages a complex series of lamellae develop throughout the entire tegmentum vasculosum in conjunction with a developing capillary network. Dark cell luminal surfaces are clearly distinguishable from the adjacent light cell surfaces by stage 37. Stages 41 and 45 show a progressive increase in dark cell surface area as well as a considerable increase in the number and size (height and diameter) of surface microvilli. The avian tegmentum vasculosum is thought to be the functional equivalent of the stria vascularis in mammals. Analysis of the morphogenesis of the tegmentum vasculosum is vital to a thorough understanding of its functional relationships with the maturing endolymphatic fluid ionic composition and endocochlear potential.

Animals↗
PubMedDate not supplied

Regulation of p27Kip1 during gentamicin mediated hair cell death.

The INK4 and Kip/Cip families of Cyclin Dependent Kinase inhibitors (CKIs) are regulators of the cell cycle. In addition, CKIS including p27(Kip1) can protect cells from apoptosis in vitro. However, little is known about protective effect of p27(Kip1) in vivo. We used systemic treatment with aminoglycosides to induce hair-cell death in the basilar papilla (BP), the auditory organ of the avian inner ear, and characterised the expression of p27(Kip1) with confocal and immunofluorescence microscopy. In contrast to the adult mammalian cochlea where p27(Kip1) is expressed only in supporting cells, p27(Kip1) is found in the nuclei of both hair cells and supporting cells in the BP of the normal, mature bird. Forty-eight hours after gentamicin treatment, hair cells with TUNEL positive nuclei and hair cells with pyknotic nuclei were both detected, suggesting many hair cells die by apoptosis. When the BP was double labelled for p27(Kip1) and myosin VIIa, a hair-cell specific protein, all dying hair cells that had been ejected from the epithelium were found to be myosin VIIa positive but negative for p27(Kip1) even though nuclear remnants were still visible. In the transition zone where partial hair-cell loss occurs, freshly ejected hair cells lying immediately above the surface of the BP no longer expressed p27(Kip1). Damaged hair cells within the epithelium in the transition zone contained p27(Kip1) in their cytoplasm but not in their nuclei. These data support recent in vitro findings suggesting that p27(Kip1) protects cells from apoptosis and that its downregulation may be a general feature of programmed cell death.

Animals↗
PubMedDate not supplied

Structural recovery from sound and aminoglycoside damage in the avian cochlea.

Hair cell regeneration in the mature avian cochlea occurs in response to trauma that causes the death of some or all of the existing hair cell population. In general, this trauma has been introduced experimentally by either sound overexposure or treatment of the bird with high doses of aminoglycoside antibiotics. When injured hair cells are ejected from the sensory epithelium, the nonsensory supporting cells respond by re-entering the cell cycle and proliferating or by transdifferentiating directly into hair cells without a mitotic event. The new hair cells mature in a manner similar to that seen during embryonic development. They make connections with the overlying tectorial membrane and the afferent and efferent cochlear nerve processes within the sensory epithelium. This structural regeneration is accompanied by a significant recovery of auditory function and thus allows the animal to regain its hearing ability. This hair cell regeneration is presumably quite beneficial to birds, whose primary means of communication is based on vocalizations and the ability to hear and comprehend them. The prevalence of hearing loss in our society and the isolating impact it has on affected individuals makes the potential for finding ways to induce a similar hair cell regeneration in humans a very tempting goal. Studies of hair cell regeneration over the last 12 years have focused on the mechanisms that regulate the process and how they could be controlled. This review will examine the structural events involved in regenerating hair cells in the avian cochlea after sound damage and aminoglycoside treatment. It will define how hair cells and nerve endings are lost and the tectorial membrane is damaged by the traumatizing stimuli and how the supporting cells and nerve fibers respond by producing new hair cells, a new tectorial membrane and new synaptic connections during recovery. Finally, it will focus on mechanisms that control the proliferation and transdifferentiation of supporting cells and the differentiation of new hair cells. This structural review is accompanied by a companion review that covers the fundamental issues concerning functional recovery in the avian cochlea associated with hair cell regeneration.

Aminoglycosides↗
PubMedDate not supplied

The molecular biology of hair cell regeneration in the avian cochlea.

The sensory cells of the ear, the hair cells, are damaged by loud noise or certain types of drugs. In the bird cochlea, new hair cells are produced to replace those that are lost. Regeneration also occurs in the vestibular epithelia of birds, fish, and mammals but does not occur in the mammalian cochlea. In order to further our understanding of the regeneration process in the bird cochlea, we have begun to identify the genes that are involved. However, the small size of this organ has made it difficult to use traditional molecular biology methods to address these problems. Recently, many molecular techniques have been adapted for use with small amounts of tissue. Northern blot analysis, the ribonuclease protection assay, semiquantitative PCR and differential display of mRNA are all techniques that are being used to greatly improve our understanding of hair cell regeneration and may eventually provide the information necessary to induce regeneration in hearing-impaired humans.

Animals↗
PubMedDate not supplied

Localization of the hair-cell-specific protein fimbrin during regeneration in the chicken cochlea.

Fimbrin is an actin-binding protein that organizes actin filaments into parallel bundles. We have used fluorescence immunocytochemistry and confocal laser scanning microscopy to demonstrate that the detection of fimbrin in the chicken basilar papilla (BP) by this method was limited to the hair cells. These experiments indicate that it was concentrated in the bundles of stereocilia. In addition, there was no evidence for the presence of fimbrin in the supporting cells, border cells, or hyaline cells. During recovery of the BP following acoustic trauma, the appearance of fimbrin in regenerating hair cells was first seen approximately 96 h after the onset of the sound exposure. This was the time at which new hair cells first appear in the BP. Reverse transcriptase polymerase chain reaction (RT-PCR) was used to detect transcription of the fimbrin gene in both control and sound-damaged BP. Semiquantitative RT-PCR indicated no detectable changes in fimbrin transcription levels 2 or 5 days after the onset of pure-tone exposure. These data indicate that fimbrin can be used immunocytochemically as a hair-cell-specific marker during regeneration in the chicken cochlea.

Animals↗