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Biomedical subjects

D Troiani

Publications and source records attributed to D Troiani.

At least 19 recordsLinked to original sources

Vascular endothelial growth factor (VEGF) expression in noise-induced hearing loss.

Noise-induced hearing loss has been associated with alterations in cochlear blood flow. Our study analyzed the expression of Vascular Endothelial Growth Factor (VEGF) and its functional receptors, Flt-1 and Flk-1, in the cochlear structures of noise-exposed and unexposed guinea pigs. VEGF is a prototypical angiogenic agent, with multiple functions on vascular biology, ranging from vascular permeability to endothelial cell migration, proliferation, differentiation, and survival. Acoustic trauma was induced by a continuous pure tone of 6 kHz, at 120 dB SPL for 30 min. Auditory function was evaluated by electrocochleographic recordings at 2-20 kHz for 7 days. Noise-induced cochlear morphological changes were studied by immunohistochemistry and scanning electron microscopy. The expression of VEGF and its receptors was examined by immunohistochemistry and western blotting analysis. The hearing threshold shift reached a level of 60 dB SPL on day 1 after trauma and underwent a partial recovery over time, reaching a value of about 20 dB SPL on day 7. Outer hair cell loss was more prominent in the area located 14-16 mm from the apex. Increased cochlear VEGF expression was observed in noise-exposed animals, in particular at the level of stria vascularis, spiral ligament, and spiral ganglion cells. No changes were observed in the expression of VEGF-receptors. Our data suggest a role for VEGF in the regulation of the vascular network in the inner ear after acoustic trauma and during auditory recovery, with potentially important clinical and therapeutic implications.

Action Potentials↗

Contribution of self-motion perception to acoustic target localization.

CONCLUSION: The findings of this study suggest that acoustic spatial perception during head movement is achieved by the vestibular system, which is responsible for the correct dynamic of acoustic target pursuit. OBJECTIVE: The ability to localize sounds in space during whole-body rotation relies on the auditory localization system, which recognizes the position of sound in a head-related frame, and on the sensory systems, namely the vestibular system, which perceive head and body movement. The aim of this study was to analyse the contribution of head motion cues to the spatial representation of acoustic targets in humans. MATERIAL AND METHODS: Healthy subjects standing on a rotating platform in the dark were asked to pursue with a laser pointer an acoustic target which was horizontally rotated while the body was kept stationary or maintained stationary while the whole body was rotated. The contribution of head motion to the spatial acoustic representation could be inferred by comparing the gains and phases of the pursuit in the two experimental conditions when the frequency was varied. RESULTS: During acoustic target rotation there was a reduction in the gain and an increase in the phase lag, while during whole-body rotations the gain tended to increase and the phase remained constant. The different contributions of the vestibular and acoustic systems were confirmed by analysing the acoustic pursuit during asymmetric body rotation. In this particular condition, in which self-motion perception gradually diminished, an increasing delay in target pursuit was observed.

Acoustics↗

Protective effects of alpha-tocopherol and tiopronin against cisplatin-induced ototoxicity.

OBJECTIVE: To investigate the possible protective effects of alpha-tocopherol and tiopronin against cisplatin-induced cochlear damage. Cisplatin ototoxicity and nephrotoxicity seem to result from the inhibition of cochlear antioxidant defences, causing an increase in the amount of reactive oxygen species. Antioxidants, such as alpha-tocopherol and tiopronin, are able to suppress lipid peroxidation, thus attenuating tissue damage. MATERIAL AND METHODS: Hartley albino guinea pigs were used. The animals were treated for 7 consecutive days with either (I) cisplatin alone, (II) cisplatin+alpha-tocopherol acetate, (III) cisplatin+tiopronin, (IV) cisplatin+alpha-tocopherol acetate+tiopronin, (V) alpha-tocopherol acetate alone or (VI) tiopronin alone. Changes in cochlear function were characterized by means of compound action potential threshold shifts. After the functional testing, tympanic bullae were removed and processed for morphological examination of the sensorineural epithelium. Renal function was evaluated by measuring serum blood urea nitrogen and creatinine levels. RESULTS: Cisplatin induced progressive high-frequency hearing loss of 40-50 dB SPL. Alpha-tocopherol and tiopronin co-therapy significantly slowed the progression of hearing loss. Treatment with alpha-tocopherol acetate or tiopronin alone was less effective. Morphological observations showed an important loss of outer hair cells and degeneration of the organ of Corti in the basal and middle turns. Injection of both alpha-tocopherol and tiopronin reduced cochlear outer hair cell loss more than treatment with a single drug. Beneficial effects of alpha-tocopherol and tiopronin on cisplatin-induced nephrotoxicity were observed. CONCLUSION: This study supports the hypothesis that alpha-tocopherol and tiopronin interfere with cisplatin-induced damage, and suggests that concurrent treatment with the two drugs can be useful in protecting against hearing loss.

Animals↗

The role of antioxidants in protection from ototoxic drugs.

A number of studies have shown that cisplatin and gentamicin ototoxic effects may result from free radical-mediated damage due to the reduction of antioxidant substances and an increased lipid peroxidation. The authors summarize the results obtained evaluating the auditory and vestibular functions and the inner ear hair cell morphology and survival after administration of antioxidant agents against cisplatin and gentamicin. In the first experiment, albino guinea pigs were treated with gentamicin (100 mg/kg per day, i.m.) alone or gentamicin (100 mg/kg per day, i.m.) plus alpha-tocopherol (100 mg/kg per day, i.m.) for 2 weeks. In a second experiment, albino guinea pigs were injected with cisplatin (2.5 mg/kg per day) or cisplatin (2.5 mg/kg per day) plus tiopronin (300 mg/kg) for 6 days. Electrocochleographic recordings were made from an implanted round window electrode. In all experiments compound action potentials (CAPs) were measured at 2-16 kHz. Changes in cochlear function were characterized as CAP threshold shifts. To evaluate vestibular function, the animals underwent sinusoidal oscillations in the dark about their vertical and longitudinal axes to evoke horizontal and vertical vestibulo-ocular reflexes (VOR). Frequency stimulation parameters ranged from 0.02 to 0.4 Hz and peak-to-peak amplitude was 20 degrees. Morphological changes were analysed by light microscopy and scanning electron microscopy. Both hearing loss and vestibular dysfunction induced by gentamicin were significantly attenuated by alpha-tocopherol. However, tiopronin co-therapy slowed the progression of hearing loss in cisplatin-treated animals and significantly attenuated the final threshold shifts. Cisplatin had little effect on the hair cells of cristae ampullares and maculae. Vestibular function was completely preserved in tiopronin co-treated animals. In conclusion, antioxidants such as alpha-tocopherol or tiopronin interfere with gentamicin and cisplatin damage and this suggests that they may be useful in preventing oto-vestibulotoxicity. Therefore, it is important to develop protective strategies that permit the avoidance of the toxic side effects of these drugs without interfering with their therapeutic effects.

Action Potentials↗

Eye instability induced by vestibular stimulation in rabbits.

The slow compensatory phases of the vestibulo-ocular reflex (VOR) in the rabbit tend to drift and the drift reverses the direction. This periodic alternating drift (PAD) has two peculiar characteristics: (1) it is induced by sinusoidal vestibular stimulation in naive animals, being evoked immediately after stimulus onset and persisting after the end of stimulation; (2) the peak velocity and period of the drift are dependent on stimulus amplitude. PAD of the rabbit has strong similarities with PAN, a periodic alternating nystagmus observed in humans with cerbellar disorders and in monkeys after nodulo-uvulectomy, although its peak velocity is smaller. It is hypothesized that PAD is due to a slight instability, caused by vestibular stimulation in darkness, of the cerebellar adaptive loop, which exerts a variable gain control on the time constant of the velocity storage integrator.

Animals↗

Functional recovery after extra-ocular muscle deafferentation in the rabbit.

The present research analysed on chronic animals the functional recovery of eye motility after impairment of the proprioceptive input at the level of the semilunar ganglion. The horizontal vestibulo-ocular reflex (HVOR) was recorded in normal pigmented rabbits before and after a partial electrolytic lesion of the semilunar ganglion. The recordings were repeated daily for 8-10 days to evaluate the recovery. Immediately after the lesion, as previously observed, HVOR slow phases were unaffected, while quick phases (QPs) showed a reduction in peak velocity and a deviation of trajectories from the horizontal plane. QP peak velocity was almost completely restored within 3-5 days, while trajectory deviation was not corrected during the observation period. Furthermore, in some animals, the variability of trajectories showed, starting from days 3-5, a progressive increase that led to a greater spatial disorganization. A process of lesion-induced plasticity takes place. but only the velocity of QPs can be recovered rapidly, while the QP trajectory impairment does not appear to be compensated substantially, which underlines a determinant role in the control of QP spatial orientation exerted by EOM proprioceptive signals.

Afferent Pathways↗

Nonlinear tension summation of different combinations of motor units in the anesthetized cat peroneus longus muscle.

The purpose of this study was to examine the linearity of summation of the forces produced by the stimulation of different combinations of type identified motor units (MUs) in the cat peroneus longus muscle (PL) under isometric conditions. The muscle was fixed at its twitch optimal length, and the tension produced by the single MU was recorded during 24- and 72-Hz stimulation. The summation analysis was first carried out for MUs belonging to the same functional group, and then different combinations of fast fatigable (FF) MUs were added to the nonfatigable slow (S) and fatigue resistant (FR) group. The tension resulting from the combined stimulation of increasing numbers of MUs (measured tension) was evaluated and compared with the linearly predicted value, calculated by adding algebraically the tension produced by the individual MUs assembled in the combination (calculated tension). Tension summation displayed deviations from linearity. S and FR MUs mainly showed marked more than linear summation; FF MUs yielded either more or less than linear summation; and, when the FF units were recruited after the S and FR MUs, less than linear summation always occurred. The magnitude of the nonlinear summation appeared stimulus frequency dependent for the fatigable FF and FI group. The relationship between measured tension and calculated tension for each MU combination was examined, and linear regression lines were fitted to each set of data. The high correlation coefficients and the different slope values for the different MU-type combinations suggested that the nonlinear summation was MU-type specific. The mechanisms of nonlinear summations are discussed by considering the consequences of internal shortening and thus the mechanical interactions among MUs and shifts in muscle fiber length to a more or less advantageous portion of single MU length-tension curves.

Anesthesia↗

Relations among motor unit types, generated forces and muscle length in single motor units of anaesthetized cat peroneus longus muscle.

The active length-tension curves of identified single motor units (MUs) belonging to peroneus longus muscle (PL) of anaesthetized adult cats were obtained by eliciting isometric single twitches and tetani. The recorded responses were evaluated by measuring the peak tension amplitude and the tension-time area at muscle lengths extending throughout the physiological length range of the muscle (mean 5.5 mm, standard deviation +/- 0.8). The muscle lengths at which each tested MU developed its maximal twitch (Ltw) and tetanic (Lte) tensions were determined and compared with the muscle length (Lo) at which the stimulation of all the alpha-axons, innervating PL and contained in L7 ventral root, developed their maximal twitch tension. The mean of single MU Ltw values was at Lo +1.08 +/- 1.1 mm. Slow MUs showed the longest values of Ltw (Lo +1.6 +/- 1.0 mm). Single MUs stimulated at tetanic frequencies presented their Lte at values shorter than Lo (Lo - 2.8 +/- 1.7 mm). Slow MUs had the shortest Lte (Lo - 3.4 +/- 1.5 mm). For all the units Lte was shorter than Ltw. Ltw and Lte were, respectively, negatively and positively correlated with the developed tension. Optimal length values also appeared to be related to the MU types. The possibility is discussed that the muscle and tendon compliances and the high non-linearities to the applied forces are the main factors which can determine the differences among Lo, Ltw and Lte values. The relationships between MU type and optimal length values are suggested to be, at least partly, an epiphenomenon due to the different contraction strengths of the various MU types.(ABSTRACT TRUNCATED AT 250 WORDS)

Anesthesia, General↗

Responses of vestibular neurons to stimulation of cortical sensorimotor areas in the cat.

Selected areas of sensorimotor cortex were stimulated with short trains adequate to evoke focal movements. Neurons belonging to the vestibular nuclear complex, including the lateral vestibular nucleus (LVN), were mainly affected by the stimulation of wrist-elbow, shoulder and cortical areas. The units responded to cortical stimulation either with a constant latency lower than 10 msec (short-latency units), or with variable latencies higher than 10 msec (long-latency units). Particular attention was paid to the first group of responses showing the involvement of direct and/or oligosynaptic facilitatory inputs from the cortical cells. Moreover, many of these responsive vestibular nuclear neurons were identified as projecting to the spinal cord.

Anesthesia↗

Tetanic tension and muscle length of motor units in cat's peroneus longus.

Length-tension curves were constructed by stimulating tetanically single motor units belonging to the peroneus longus muscle. The lengths at which the motor units showed the maximal tension appeared to be shorter than the length at which the whole muscle developed the maximal twitch tension. Moreover, the optimal lengths appeared to be different for the different motor unit types, corresponding to very short muscle lengths for Slow units and to slightly higher lengths for the Fast Fatiguable and the Fatigue Resistant units.

Animals↗

Converging cerebellofugal inputs to the thalamus. I. Mapping of monosynaptic field potentials in the ventrolateral nucleus of the thalamus.

The extent of thalamic projections from punctate sites in the cerebellar nuclei was examined in 22 acutely prepared cats by mapping monosynaptic field potentials evoked in the ventrolateral (VL) nucleus by stimulation of the interpositus and dentate nuclei (IN and DN). The monosynaptic field potentials were evoked in the VL by low current stimulating pulses applied at high frequency to these cerebellar nuclei. Quantification of the projections was possible since the conditions of stimulation and recording were strictly controlled. The incoming volley recorded in the brachium conjunctivum caudally to the VL was also analysed. It was composed of two amplitude peaks with different latencies, corresponding to two groups of fibres conducting at 60-90 m/s and 20-25 m/s respectively. The negative field potentials in VL also showed two amplitude peaks and different latencies. The differences in latency between the first and second peaks in the presynaptic and postsynaptic field potentials are compatible with the possibility that both groups of afferent fibres may be monosynaptically connected to VL relay cells. The cerebello-thalamic projections were mapped and their density gradient was established. Two or three small thalamic strips of dense projections surrounded by a large zone of weaker projections were observed to emerge from each punctate cerebellar site. In the discussion of the functional significance of these findings, it is suggested that this organization might constitute a modulatable morphological support for a mechanism focalizing the cerebello-cortical inputs.

Action Potentials↗

Converging cerebellofugal inputs to the thalamus. II. Analysis and topography of thalamic EPSPs induced by convergent monosynaptic interpositus and dentate inputs.

A large number of projections from cerebellar nuclei converge onto individual neurones in the thalamic relay to the motor cortex. Among the thalamic cells receiving cerebellar inputs, 75 out of 153 (50%) were found to be influenced by monosynaptic inputs from at least two cerebellar nuclei and 2 (1.5%) from three nuclei (the interpositus, dentate and fastigial nuclei). The pathways of the inputs converging on the same unit were found to be monosynaptic in 67 thalamic neurons, and disynaptic in the eight others. The monosynaptic nature of the majority of the pathways was proved by analysing the synaptic delay and the spatial and temporal summation. The 67 thalamic neurons receiving direct convergent influences were found to be distributed within the central portion of the VL. Forty-four of them give off projections to all the cortical areas, although a slightly higher proportion is to be found within the motor cortex shoulder area than elsewhere (medial part of area 4). Consequently, the specific function of the neurons receiving direct, convergent cerebellar inputs is not to control one particular part of the musculature but on the contrary, to transmit reciprocal facilitatory effects between the interpositus and dentate nuclei to all the cortical motor subdivisions. Maps summarizing monosynaptic responses obtained with semi-chronic preparations were drawn at thalamic and cortical levels. Each VL neuron was found to be a point where the two cerebellar circuits converge and may interact: the cerebrocerebellar circuit, which passes through the dentate nucleus, generates a feedward motor command: this can either modify or be modified by the feedback peripheral loop, which passes through the interpositus nucleus.

Afferent Pathways↗

Cortical modulation of the nucleus of the optic tract in the rabbit.

We analyzed in rabbits the relationships between the temporooccipital nystagmogenic cortex (NGC)--the region sited at the border between cortical areas 17, 21, and 22--and the nucleus of the optic tract (NOT). Two experimental approaches were used: (a) eye movement analysis before and after electrolytic lesion of the NOT region provided an indication of the importance of the NOT for the interaction between the ocular nystagmus elicited by natural optokinetic stimulation (OKN) and the nystagmus evoked by electrical stimulation of the nystagmogenic area; (b) NOT direction-selective and velocity-sensitive units were tested with single shock or repetitive electrical stimulation of the nystagmogenic region. Single-shock stimulation evoked single or multiple spikes in 50% of NOT units analyzed and repetitive stimuli induced prolonged facilitation and inhibitory rebounds in 70% of the units tested. Comparison of orthodromic activation latencies of the NOT cells (3.2 and 6.1 ms) after cortical stimulation and of antidromic activation latencies of cortical nystagmogenic units (2.6 ms) after NOT shocks, suggested monosynaptic as well as polysynaptic connections between the temporooccipital cortex and the NOT. The existence of such cortical-NOT linkage indicates that the NOT is intercalated between the cortex and the oculomotor centers and represents the most probable site of interaction of the cortical nystagmus pathway with the optokinetic reflex arc.

Animals↗

Role of vestibular nuclei in 'optic' nystagmus.

Horizontal eye nystagmus beating towards the stimulated side ('optic' nystagmus) was evoked in 25 guinea pigs by stimulating an optic nerve. The complete ablation of the vestibular nuclear complex abolished this nystagmus. In a second group of 15 animals, the behavior of 63 vestibular neurons identified electrophysiologically was analyzed during eye nystagmus; most of these neurons responded with a tonic increase in discharge rate to stimulation of the optic nerves. Units sensitive to the direction of optic and labyrinthine nystagmus were also identified.

Animals↗