[Ototoxicity of cisplatin].

The objective of this publication is to summarize "classical" and modern concepts of pathogenesis, clinical features of cisplatin ototoxicity, its screening, and prophylaxis. It is argued that pathogenesis of a cisplatin-induced injury to the inner ear shares common features with the ototoxic mechanisms of action of other pharmaceuticals even though it is characterized by certain important differences. The authors consider the mechanisms of ototropicity, specific cytochemical aspects of cisplatin cytotoxicity that aggravate risk factors, and genetic predisposition to the development of iatrogenic problems. The data are presented on monitoring and experimental aspects of otoprotection for the prevention of cisplatin-induced damage to the auditory analyzer.

[A model for the study of the ototoxic effects of drugs in an experiment]. / Model' dlia izucheniia ototoksicheskikh éffektov lekarstvennykh sredstv v éksperimente.

The authors compared sensitivity of the acoustic analyzer elements to ototoxic drugs in cat experiments. The model proposed assesses primary responses of the brain cortical acoustic zone (BCAZ) to sound stimulation. The drugs effect on the analyzer's periphery was determined from changes in bioelectric responses of the cochlea to sound stimulation (microphone potential, potential of the acoustic nerve action). The arguments are presented for feasibility of using primary BCAZ responses evoked by electric stimulation of thalamocortical radiation fibers coming from the medial geniculate body for examination of the drug effects on the analyzer's cortex. Parallel registration of the above bioelectrical reactions in the same animal for a long time makes it possible to compare sensitivity of different elements of the acoustic analyzer to ototoxic medication.

Brain stem integration of vocalization: role of the midbrain periaqueductal gray.

1. The contribution of the midbrain periaqueductal gray (PAG) to the central regulation of vocalization was investigated by analyzing the electromyographic (EMG) changes in respiratory, laryngeal, and oral muscles evoked by microinjection of D,L-homocysteic acid (DLH) in the PAG of unanesthetized, precollicular decerebrate cats. Moderate to large (6-40 nmol) doses of DLH evoked natural-sounding vocalization as well as increases in inspiratory depth and respiratory rate. 2. Two basic types of vocalization were evoked, each associated with a distinct and characteristic pattern of respiratory, laryngeal and oral EMG changes. Type A vocalization (voiced sounds such as howl/mew/growl) was characterized by excitation of the cricothyroid (CT) and thyro-arytenoid (TA) muscles, and inhibition of the posterior crico-arytenoid (PCA) muscle, whereas type B vocalization (unvoiced hiss sounds) was characterized by excitation of the PCA and TA muscles and no significant activation of the CT muscle. In addition, stronger expiratory (external oblique, internal oblique, internal intercostal) EMG increases were associated with type A responses, and larger increases in genioglossus and digastric muscle activity were associated with type B responses. 3. Microinjections of small doses of DLH (300 pmol-3 nmol), also evoked patterned changes in muscle activity (usually without audible vocalization) that, although of lower amplitude, were identical to those evoked by injections of moderate to large DLH doses. In no such experiments (175 sites) were individual muscles activated by small dose injections of DLH into the PAG. Further, type A vocalization/muscle patterns were evoked from PAG sites caudal to those at which type B vocalization/muscle patterns were evoked. 4. Considered together these results indicate: that the PAG contains topographically separable groups of neurons that coordinate laryngeal, respiratory, and oral muscle patterns characteristic of two fundamental types of vocalization and that the underlying PAG organization takes the form of a representation of muscle patterns, rather than individual muscles. 5. The patterns of EMG activity evoked by excitation of PAG neurons were strikingly similar to previously reported patterns of EMG activity characteristic of major phonatory categories in higher species, including humans (e.g., vowel phonation, voiceless consonant phonation). These findings raise the possibility that the sound production circuitry of the PAG could well be utilized by cortical and subcortical "language structures" to coordinate basic respiratory and laryngeal motor patterns that are necessary for speech.

Effect of muscimol microinjections into the prepositus hypoglossi and the medial vestibular nuclei on cat eye movements.

1. For horizontal eye movements, previous observations led to the hypothesis that the legendary neural integrator necessary for correct gaze holding, adequate vestibuloocular reflex (VOR), and optokinetic nystagmus, was located in the region of the complex formed by the nucleus prepositus hypoglossi (NPH) and the medial vestibular nucleus (MVN). 2. The aim of the present study was to test the respective contributions of the NPH, of the rostral part of the MVN, which contains most second-order vestibular neurons, and of the central part of the MVN to the horizontal integrator. 3. An injection of muscimol was used to inactivate each of these three zones in the cat's brain. Muscimol is a gamma-aminobutyric acid (GABA) agonist. By binding to GABAA receptors, it induces a hyperpolarization of the neurons that nullifies their activity. Muscimol was injected into the brain stem of the alert cat through a micropipette by an air pressure system. 4. The search coil technique was used to record spontaneous eye movements and the VOR induced by rotating a turntable at a constant velocity. VOR was analyzed by a new method: transient analysis of vestibular nystagmus. 5. A unilateral injection of muscimol into the NPH induced a bilateral gaze-holding failure: saccades were followed by a centripetal postsaccadic drift. A vestibular imbalance was also present but it was moderate and variable. The VOR responses were distorted drastically. Through transient analysis of vestibular nystagmus, that distortion was revealed to be due more to a failure of the neural integrator than to an alteration of the vestibular input to the neural integrator. The responses to a rotation either toward the injected side or in the opposite direction were asymmetrical. The direction of that asymmetry was variable. 6. A unilateral injection of muscimol into the rostral part of the MVN caused a vestibular imbalance: in complete darkness, a nystagmus appeared, whose linear slow phases were directed toward the side of injection. 7. A unilateral injection of muscimol into the central part of the MVN induced a syndrome where a severe bilateral gaze-holding failure was combined with a vestibular imbalance. In the light, saccades were followed by a bilateral centripetal postsaccadic drift. In complete darkness, a nystagmus was observed, whose curved slow phases were directed towards the side of injection. The VOR responses were distorted drastically. Here again, that distortion was revealed by our analysis to be due more to a failure of the neural integrator than to an alteration of the vestibular input to the neural integrator.(ABSTRACT TRUNCATED AT 400 WORDS)

[Aberrations of cortical and subcortical integration during chronic administration of haloperidol to the dog]. / Perestroiki korkovo-podkorkovoi integratsii u sobak pri khronicheskom vvedenii galoperidola.

The character of evoked potentials (EPs) dynamics to signal light stimulus during elaboration of avoidance reaction, allows to assert that during formation of adaptive activity functional balance is established of sensory and integrative-triggering brain parts or functional balance of "motor" and "sensory" integration regimes. Each of the studied subcortical structures is characterized by simultaneous but specific functioning both in the motor and sensory regimes; such conclusion is based on different dynamics of their EPs parameters: the changes of ones correspond to EPs dynamics in the visual cortical area, of the others--in the motor area. During chronic haloperidol administration, the reorganizations of intercentral relations are observed in 10--12 days after the beginning of drug administration. They may be considered as a succession of disturbances of functional balance between "sensory" and "motor" integration regimes: at first the sensory regime domination appears in which subcortical structures are chiefly and uniformly involved (ncd, pall and n. acc.); "motor" regime is weakened; then, as a result, a distortion of the "motor" regime of integration takes place. In this case a bradykinesia is developed.

[Effect of thiamine on auditory evoked potentials of the guinea pig]. / Deistvie tiamina na slukhovye vyzvannye potentsialy u morskoi svinki.

Application of thiamine (1 X 10(-11)-1 X 10(-3) mol/l) on the membrane of cochlear round window increased the amplitude and decreased the latency of the auditory nerve action potential, waves I and II of brainstem auditory-evoked electrical potentials in response to acoustic clicks of different intensity. The mechanism of thiamine action on auditory-evoked electric potentials is discussed.

[Effect of cholinolytics on the functional lability of the visual analyzer in cats]. / O vliianii kholinolitikov na funktsional'nuiu labil'nost' zritel'nogo analizatora koshek.

The effect of aminoethers of derivates of glycolic acid (glipine and amizil) in doses of 0.1--5 mg/kg and of derivates of acetic acid (diphacyl and thropacin) in doses of 10--40 mg/kg on bioelectrical activity of the retina was studied in experiments on 10 intact cats. To control the effect of cholinolytics, electrodes were chronically implanted in the visual cortex and EEG ws recorded. It was noted that the frequency of white, yellow, green and blue photic stimuli is reproduced on ERG within the range from 1 to 23 c/s both before the administration of cholinolytics and during their action in all of the used doses. Flash rhythm reproduction was not disturbed (in spite of an increase in the waves' amplitudes in the retinal background bioelectrical activity) following administration of cholinolytic substances. All cholinolytics in all of the studied doses caused in the EEG of the visual cortex an increase in waves' amplitude, i. e. a synchronization.

[Effect of strychnine and picrotoxin on the development of habituation in the visceral analyzer]. / Vliianie strikhnina i pikrotoksina na razvitie privykaniia v vistseral'nom analizatore.

Effects of strychnine and picrotoxin on habituation of cortical potentials evoked by repeated stimulation of the splanchnic nerve were studied in anesthetized and immobilized cats. I. v. administration of strychnine (o.1 mg/kg) or picrotoxin (0.4 mg/kg) did not alter the decrement in evoked potentials. Larger doses of strychnine (0.3 or 0.6 mg/kg) and picrotoxin (0.8 or 2.0 mg/kg) did not block the habituation effects either. Picrotoxin applied to 2nd somatosensory area of the cortex effected amplitude of the negative component of the evoked potentials. Possible mechanisms of the habituation process are discussed.