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Biomedical subjects

M Lenoir

Publications and source records attributed to M Lenoir.

At least 55 records · Page 3Linked to original sources
PubMed1990

Glutamate neurotoxicity in the cochlea: a possible consequence of ischaemic or anoxic conditions occurring in ageing.

Glutamate is considered to be one of the most common neurotransmitters in the fast excitatory synapses in the central nervous system. On the other hand, its excitotoxic properties are increasingly cited to explain some of the brain damage linked with hypoxia and ischaemia: i.e., those that occur frequently in ageing. An excess release of glutamate could, either directly or indirectly, activate receptors on the postsynaptic neuron, causing ion influxes accompanied by a massive entry of water, which would lead to an acute swelling of dendrites. In addition, calcium influx deregulates calcium homeostasis, which could lead to cell death. In the cochlea, glutamate is now considered to be one of the best candidates to mediate neurotransmission between inner hair cells (IHCs) and the auditory nerve dendrites. Among the variety of anatomical and physiological findings supporting the glutamate hypothesis, is the striking similarity of acute damage in the organ of Corti caused by exposure to a glutamate analogue (kainic acid), or by hypoxia, or even by an intense loud noise. In all cases an immediate swelling is observed, specifically affecting the radial afferents below the IHCs. The best explanation for this swelling is related to glutamate (or glutamate analogue) excitotoxicity. Thus, some of the cochlear damage that occur with ageing, especially the loss of the radial afferent fibres and type I ganglion cells, might well be attributed to glutamate excitotoxicity linked to vascular atrophy. The present paper discusses this hypothesis.

Aging↗
PubMed1987

Stereocilia and tectorial membrane development in the rat cochlea. A SEM study.

Maturation of the rat cochlea, from postnatal days 2 to 60, was studied using scanning electron microscopy (SEM), with emphasis on stereocilia and tectorial membrane (TM). Two days after birth, the organ of Corti was very immature. An adult appearance of its surface was observed by day 16 in the basal turn, and by the end of the 3rd postnatal week in the apex. Stereocilia started their development first on inner hair cells. By contrast, the apical pole of outer hair cells ended its maturation before that of inner hair cells. Top-links were detected very early in inner hair cell stereociliary development (postnatal day 2). Marginal pillars temporarily attached the TM to the organ of Corti; they disappeared first in the apical region. This transient attachment seems to play a role in the coupling of outer hair cells to the TM, as prints of their longest stereocilia appeared at the undersurface of the TM by the same time. Moreover, these prints were more clear and regular at the base than at the apex of the cochlea. Results are discussed in relation to ultrastructural and functional data on rat cochlea maturation.

Animals↗
PubMed1987

Dose-dependent changes in the rat cochlea following aminoglycoside intoxication. I. Physiological study.

The dose-dependent effects of amikacin on the rat cochlea were studied electrophysiologically using CAP audiograms, amplitude and latency-intensity curves, and CAP tuning curves using a forward masking procedure. The animals were given a daily subcutaneous injection of amikacin in doses ranging from 100 to 1000 mg/kg, for five consecutive days, and were tested one month after the end of the treatment. No functional evidence of ototoxicity was found in animals treated with 100 and 200 mg/kg per day doses of amikacin. The first electrophysiological changes were observed with doses of 300-600 mg/kg per day. They consisted of a broadening of the tip and a hypersensitivity of the tail of the CAP tuning curves, without a change in the CAP threshold sensitivity and latency. Animals treated with 700 mg of amikacin showed an elevation of the tip of the CAP tuning curves and an increase in CAP latency. The classical feature of antibiotic ototoxicity was observed in animals given 800 mg/kg per day of amikacin with an increase in CAP threshold sensitivity and latency, a disruption of the CAP amplitude-intensity function, and a clear hyposensitivity of the CAP tuning curves. These results are discussed in the light of anatomical findings described in a companion paper.

Acoustic Stimulation↗
PubMed1987

Dose-dependent changes in the rat cochlea following aminoglycoside intoxication. II. Histological study.

The structural damages induced by a range of amikacin doses have been studied with SEM and TEM in the adult rat cochlea. Six groups of rats were given daily subcutaneous amikacin injections of either 200, 400, 600, 700, 800, or 1000 mg/kg per day for five consecutive days. Observations were made one month after the end of treatment, following functional recordings [(1987) Hear. Res. 26, 191-197]. In the group treated with 200 mg/kg per day, neither SEM nor TEM revealed any cochlear abnormalities. In the 400-mg group, the only damages were cytoplasmic abnormalities in the OHCs. Changes in the OHC stereocilia occurred at higher doses and were always associated with severe alterations of the underlying cell body. The first missing hair cells were OHCs in the apical regions of the cochleas of the 600-mg group. In the 700-mg group, the loss of OHCs extended to the middle and basal regions, mainly in the third row. By contrast, in the 800- and 1000-mg groups, the usual pattern of hair-cell degeneration was found. Loss of hair cells was greatest in the basal cochlear regions, where the first row of OHCs was more extensively destroyed. These results indicate that metabolic disorders (only visible with TEM) precede stereociliary alterations. Under SEM, the pattern of hair cell degeneration appeared to depend on the dose of the drug. The study clearly demonstrates that both SEM and TEM are needed to determine the true condition of hair cells after drug intoxication.

Amikacin↗
PubMed1987

Development of 2f1-f2 otoacoustic emissions in the rat.

2f1-f2 otoacoustic emissions have been recorded from the rat cochlea during its development. Acoustic responses were recorded at 3, 5 and 7 kHz using a fixed value of the f2/f1 ratio (= 1.17). The first 2f1-f2 acoustic responses were obtained at 12 days after birth for 2f1-f2 = 7 and 5 kHz, and 2 days later for 2f1-f2 = 3 kHz. Adult-like patterns of the acoustic responses were achieved by day 18 for 2f1-f2 = 3 kHz, by day 20 for 2f1-f2 = 5 kHz and by day 28 for 2f1-f2 = 7 kHz. These results are discussed in relation to the available anatomical and functional data on the cochlear development of the rat. The delayed appearance of the 3 kHz acoustic responses might be related to the basal-to-apical gradient of morphological cochlear maturation. The fact that the 2f1-f2 otoacoustic emissions reached adult characteristics from the low to high frequencies is consistent with the development of the tuning properties of the basilar membrane. The long development of the 2f1-f2 acoustic responses at 7 kHz suggests that the organ of Corti undergoes subtle changes well after the end of its apparent maturation.

Aging↗
PubMed1987

[Oto-acoustic emissions. II. Spontaneous oto-emissions: results in normal subjects or patients with tinnitus].

Sounds can be emitted by the cochlea in the absence of any stimulation. This phenomenon is called spontaneous oto-acoustic emissions (SOAEs) and they can be recorded in the external auditory canal using a sensitive microphone. This phenomenon seems to be due to an abnormality of the active cochlear mechanisms. SOAEs have been studied in 140 human subjects, 140 of them suffering with tinnitus, while 80 were used as the control group. SOAEs have been studied as a function of age, and of the audiometric state. Possible relationships between SOAEs and tinnitus have also been studied. This study shows the interest of recording SOAEs for an early diagnosis of cochlear dysfunction. It also shows that there is no clear correlation between tinnitus and SOAEs.

Adolescent↗
PubMed1986

In vitro and in vivo effects of piroxicam on rat polymorphonuclear responsiveness after induction of two acute non-specific inflammatory reactions.

The effect of piroxicam on rat polymorphonuclear leucocytes (PMN) has been studied in vitro and in vivo after the induction of two acute, non specific inflammatory reactions (pleurisies induced by calcium pyrophosphate crystals (CaPP) or isologous serum). An inhibition of chemotaxis by piroxicam has been demonstrated by two techniques, the filter and agarose assays in vivo and in vitro. An inhibition of random cell migration has been observed only at the higher drug concentration using agarose assay with CaPP-elicited cells. Piroxicam also inhibited superoxide anion generation and O2 consumption of CaPP- and serum-elicited cells. These findings suggest that piroxicam may have a direct effect on PMN responses and that this activity could, at least in part, contribute to its anti-inflammatory properties.

Acute Disease↗
PubMed1986

Modifications of cochlear microphonic frequency responses following transient changes of hydrostatic pressure in the perilymph.

Cochlear microphonic potential was recorded with differential electrodes implanted in the various turns of the guinea-pig cochlea. Isointensity frequency responses were plotted in normal conditions and after excessive displacements of the cochlear partition. These displacements were provoked by changes of hydrostatic pressure in the perilymph of scala tympani or scala vestibuli. Typical modifications of the frequency response were observed. The most noticeable was a division in two parts of the response zone which suggested the existence of two resonance peaks. Scanning electron microscopy revealed that changes of hydrostatic pressure provoked alterations of the stereocilia in the outer rows of external hair cells, probably in relation with a decoupling of the tectorial membrane from the organ of Corti. These results are discussed in terms of possible alterations of cochlear micromechanics.

Animals↗
PubMed1986

Tachykinins: effects on motility and metabolism of rat polymorphonuclear leucocytes.

Chemotactic and chemoluminescent activities of substance P, substance K, kassinin and the substance P fragments SP 4-11, SP 7-11, SP 1-4 have been investigated in order to identify the minimum active molecular structure responsible for rat polymorphonuclear activation. Substance P, SP 4-11 and SP 7-11 stimulated directed locomotion (chemotaxis) and were found to be active also in the chemoluminescence assay while SP 1-4 had no effect. Moreover, all peptides, except substance K and SP 1-4, inhibited the chemotactic response of polymorphonuclears to the peptide formyl-methionyl-leucyl-phenylalanine and, to a minor extent, also to leukotriene B4. A maximum of activity was observed with the C-terminal sequence SP 4-11. Substance K was found to be inactive. Kassinin exhibited a weak chemotactic effect and exerted a slight inhibition of attracting activity of peptide-formyl-methionyl-leucyl-phenylalanine. Considering that substance P and related peptides are active only at very high concentrations, it cannot be affirmed that these agents activate specific receptors. If receptors are involved, they would be of the SP-P type, since substance K is inactive.

Animals↗
PubMed1985

Kainic acid selectively alters auditory dendrites connected with cochlear inner hair cells.

Cochleas of adult guinea pigs and rats, and 6-day-old rat pups, were injected, through the round window, with 2 microliters of artificial classical Konishi perilymph containing 1 nmol kainic acid (KA). 5 min later, they were fixed, removed, and processed for electron microscopy. In all KA-treated cochleas, the injection resulted in a severe swelling of auditory dendrites below the inner hair cells (IHCs). Below the outer hair cells (OHCs), the swelling appeared only in the 6-day-old rats, not in adult animals. These results are significant in three different ways: (1) They confirm the strong difference between afferents innervating the IHCs and the OHCs in adult cochleas. (2) They shed some light on the synaptic plasticity found at the OHC level during synaptogenesis. (3) They support the hypothesis that glutamate, or a related substance, is the IHC neurotransmitter.

Age Factors↗
PubMed1985

Distortion product otoacoustic emissions in hearing-impaired mutant mice.

The acoustic intermodulation distortion product (2f1-f2) was recorded in the ear canal of two different types of normally hearing mice and in four different types of hearing-impaired mutant mice. In the normally hearing animals, primary tones at levels of 60- to 100-dB SPL evoked distortion product emissions (DP's) at 20-50 dB below the primary levels. In the hearing-impaired mutants the level was dependent on the particular type of auditory dysfunction associated with the mutation. In both the deafness and the viable dominant spotting mutants, where either the whole organ of Corti or the stria vascularis is affected by the mutation, no DP's could be detected. The quivering mutant has a central auditory dysfunction associated with the nuclei of the superior olivary complex and the lateral lemniscus, with apparently normal cochlear function. DP's at levels and thresholds similar to those in normally hearing animals were recorded in quivering mice. The Bronx Waltzer mutant has a full complement of outer hair cells but only about of 20%-25% inner hair cells. DP's of small amplitude were recorded but the thresholds were raised by about 30 dB. The data suggest that the 2f1-f2 emission can be used as a noninvasive monitor of cochlear function.

Acoustic Stimulation↗
PubMed1985

Effect of piroxicam on the chemotaxis and random migration of polymorphonuclear leucocytes after induction of immune and non immune inflammations.

The effect of piroxicam on the chemotaxis and random migration of rat polymorphonuclear leucocytes was investigated with two techniques of assessment (filter and agarose assay) under various experimental conditions. The drug was administered in vivo or tested in vitro on polymorphonuclears collected in the pleural cavity after induction of an immune (reverse passive Arthus reaction) or an acute non-specific inflammation (pleurisy induced by a suspension) (1%) of calcium pyrophosphate crystals (CaPP). In all cases a dose-dependent inhibition of chemotaxis was observed, more striking in the case of CaPP elicited cells which were more reactive than cells collected after the induction of the Arthus reaction. No modification of random migration appeared using the filter assay while a slight inhibition was demonstrated at the higher dose using the agarose assay.

Animals↗
PubMed1984

Age-related structural investigation of the Bronx waltzer mutant mouse cochlea: scanning and transmission electron microscopy.

Cochleas of mice homozygous for the Bronx waltzer gene (symbol bv) were investigated using scanning (SEM) and transmission (TEM) electron microscopy. An age-related study was done from birth to postnatal day 100. With SEM, the arrangement of hair cells confirmed the unique feature of the bv/bv cochlea: the inner hair cells (IHCs) were either absent or abnormally haired but the outer hair cells (OHCs) appeared normal. No significant difference was observed with age. Using TEM, the remaining (20-25%) IHCs could be divided into two groups: normal-looking IHCs but with an abnormal synaptic pole, and abnormal, abortive-like IHCs. Very little if any sign of degeneration was observed whatever the age. OHCs displayed an almost normal cytology and pattern of innervation. The neurons of the spiral ganglion were very rare, even at birth. These findings suggest that the bv mutation should rather be classified in another group, than 'degenerative'. The persistence of normal structures at OHC level is discussed in light of the cochlear physiology of the bv/bv: it again raises the question of the real role of OHCs in the peripheral auditory mechanisms.

Aging↗
PubMed1983

The pattern of sensorineural degeneration in the cochlea of the deaf shaker-1 mouse: ultrastructural observations.

Experiments were done to extend existing knowledge on the nature and course of postnatal sensory and neural changes in the inner ear of shaker-1 mutant mice. Mice, 3-, 6-, 10-, 12-, 18-, and 30 days old, homozygous for the sh-1 gene, were studied using transmission electron microscopy. The data indicate retarded development coupled with the early onset of progressive degeneration in Corti's organ its nerve supply, and the cells of the spiral ganglion. Especially noteworthy are the following: in 3-day-old mice both outer hair cells and spiral ganglion cells are already abnormal. The latter are especially loosely ensheathed by glial cells and are in direct contact with nerve fibers. Outer hair cells contain vacuoles and lysosomes. By 6 days of age inner hair cells come to be similarly affected. By 18 days most of the afferent nerve supply of the organ of Corti has degenerated. The behavior of efferents within the organ is complex. Efferents arrive late (day 12) at the outer hair cells, they are few in number, form only immature synapses with the cell, and they subsequently degenerate. In contrast, the efferent nerve supply of the inner hair cell appears normal, if not over-abundant. The simultaneous occurrence of organ of Corti and spiral ganglion cell anomalies is discussed in terms of the role of sensorineural interactions in the expression of genetic defects affecting the inner ear. The selective degeneration of efferents to outer hair cells is viewed as being consistent with the hypothesis that there are two independent efferent systems which innervate the two types of cochlear sensory hair cells.

Animals↗
PubMed1983

Early degeneration of sensory and ganglion cells in the inner ear of mice with uncomplicated genetic deafness (dn): preliminary observations.

Deafness (dn/dn) mouse cochlea was investigated by electron microscopy in order to detect the first postnatal signs of histopathology. At birth, the inner hair cells (IHCs) showed abnormal vacuolization, afferent dendrites at IHC level appeared swollen and devoid of cytoplasmic content, and most of the neurons of the spiral ganglion contained an abnormal smooth endoplasmic. At day 7, these abnormalities had greatly increased, especially in the spiral ganglion neurons where large patches of filamentous material were found. These observations can account for the permanent electrophysiological deafness of dn/dn mice. Moreover, these data, showing early cytological abnormalities in both the IHCs and the spiral ganglion neurons, indicate that it is difficult to simply classify the deafness mutation as being 'degenerative'; some 'morphogenetic' processes are likely also involved.

Animals↗
PubMed1983

Comparative ototoxicity of four aminoglycosidic antibiotics during the critical period of cochlear development in the rat. A functional and structural study.

The comparative ototoxicity of four aminoglycosides (amikacin, dibekacin, gentamicin and tobramycin) was evaluated in the rat during the critical period of cochlear development. Newborn rats received a daily subcutaneous injection of one of the four antibiotics for 8 consecutive days, starting on day 8 after birth (amikacin: 225 mg/kg, dibekacin: 60 mg/kg, gentamicin and tobramycin: 45 mg/kg). Evaluation of ototoxicity was assessed one month after the end of the treatment using cochlear recordings (action potential and cochlear microphonic), surface preparations and scanning electron microscopy. No functional or structural evidence of ototoxicity was found in animals treated with dibekacin. Tobramycin had a weak ototoxic effect characterized by a slight increase in N1 latency and moderate damage to OHC stereocilia (fusion and formation of giant cilia). Gentamicin-treated animals demonstrated more severe evidence of ototoxicity including increased thresholds for CM, and a higher incidence of missing hair cells and damage to OHC stereocilia. The maximal cochlear damage was observed in amikacin-treated animals: both AP and CM thresholds were severely impaired, cell counts and SEM showed extensive loss of hair cells.

Action Potentials↗
PubMed1983

[Stimulation of mitotic activity of bone marrow cells in an acute inflammatory reaction. Implication of serum factors].

A nonspecific acute inflammatory reaction, induced in mice by an intrapleural injection of dextran, is able to increase, in vivo, the mitotic index of bone marrow cells. The transfer of this phenomenon to normal mice can be obtained by the injection of pure or diluted sera from animals developing an acute non-specific inflammation. This activity may also be found in the serum of normal mice but at a much lower level. The stimulatory activity is also observable in vitro when bone marrow cells are incubated with inflammatory serum. This activity is recoverable after ultrafiltration in the fraction less than 10 000 daltons. These results suggest the existence in sera of stimulating factors for hematopoiesis and furthermore that these stimulatory activities are increased during the process of inflammation.

Acute Disease↗