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W K Boyes

Publications and source records attributed to W K Boyes.

52 records · Page 3Linked to original sources
PubMed1984

Chlordimeform produces profound, selective, and transient changes in visual evoked potentials of hooded rats.

Rat visual function was tested after acute exposure to chlordimeform (CDM), a formamidine insecticide/acaricide. Adult male Long-Evans rats were surgically implanted with epidural recording electrodes overlying visual cortex and tested 1 week later. Pattern reversal-evoked potentials (PREPs), flash-evoked potentials (FEPs), and FEP recovery ratios were measured after acute CDM administration. Averaged recordings obtained during 200 reversals of a black-and-white square wave grating comprised the PREPs, and those obtained during 128 paired strobe lamp flashes comprised the FEPs. In the first study, which examined dose-response relationships, i.p. injections of 0 (saline), 5, 15, or 40 mg/kg CDM-HCl were administered 30 min prior to testing. The PREP amplitudes showed large dose-related changes in the CDM-treated rats. PREP N1P1 and P1N3 peak-to-peak amplitudes increased more than 200% in the 40 mg/kg group. In contrast, FEP amplitudes and FEP recovery ratios were unchanged by CDM. Both PREP and FEP peak latencies were increased by CDM in dose-related fashions. In the second study, which examined the time course of CDM action, PREPs and paired-pulse FEPs were recorded 3, 6, and 24 h after dosage with either 0 or 40 mg/kg CDM. All evoked potential changes were large at 3 and 6 h, but had returned to control values by 24 h. In summary, acute exposure to CDM temporarily increased both the amplitude and latency of PREPs, but only the latency of FEPs.

Amidines↗
PubMed1983

Pattern reversal visual evoked potentials in awake rats.

A method for recording pattern reversal evoked potentials (PREPs) from awake restrained rats has been developed. The procedure of Onofrj et al. [26] was modified to eliminate the need for anesthetic, thereby avoiding possible interactions of the anesthetic with other manipulations of interest. Rats were restrained in a harness and placed in front of a pattern generating TV screen displaying a black and white alternating square wave grating. Using various stimulation and recording parameters, normative data are presented from 141 adult male Long-Evans hooded and 11 adult male Sprague-Dawley albino rats. Reliable waveforms were recorded with five identifiable peaks. The labels and mean latencies of these peaks in hooded rats were: N1, 47.3 msec; P1, 65.7 msec; N2, 83.3 msec; P2, 94.4 msec; and N3, 129.8 msec. Spatial acuity functions generated with PREPs gave acuity estimates which corresponded closely to values determined behaviorally for hooded and albino rats [4,11].

Animals↗
PubMed1983

Hypothermia and chloropent anesthesia differentially affect the flash evoked potentials of hooded rats.

Anesthetics and body temperature alterations are both known to alter parameters of sensory-evoked responses. However few studies have quantitatively assessed the contributions of hypothermia to anesthetic-induced changes. Two experiments were performed. In the first, chronically implanted rats were injected with either 0, 0.05, 0.10 or 0.20 ml Chloropent/100 g b.w., while body temperature was maintained. Flash evoked potentials recorded 30 min later showed increased latencies but only minor (not statistically significant) changes in amplitude. In the second experiment the same rats were anesthetized with 0.35 ml Chloropent/100 g b.w. and rectal temperature was systematically varied between 31 degrees C and 37 degrees C. Over the ranges of temperature and anesthetic employed, latencies increased more extensively with hypothermia than with anesthesia. P1N1 amplitude doubled when temperature was lowered to 31C, but P2N2 and N2P3 amplitudes declined over the same temperature range. Anesthetic-induced changes in peak-to-peak amplitude did not reach statistical significance when body temperature was constant. The findings suggest that previously reported alterations in evoked potentials following anesthesia may have been confounded with hypothermia.

Anesthetics↗
PubMed1983

Use of neurophysiological challenges for the detection of toxicity.

The concept that a challenge to a system may overcome compensatory mechanisms and thereby reveal otherwise hidden neurotoxicant-induced damage is reviewed from a neurophysiological perspective. Two broad classes of neuronal challenges, poststimulation neuronal recovery processes and epileptogenesis, are discussed in terms of their potential value for detection and characterization of neurotoxicity. Neuronal recovery studies have typically involved presentation of pairs or trains of stimuli with various interstimulus intervals. Studies involving simple (e.g., monosynaptic) systems may allow mechanistic interpretation of alterations. Paired-pulse studies involving more complex (e.g., polysynaptic sensory) systems have detected alterations more readily than other electrophysiological methods, but interpretation may not be as straightforward as the monosynaptic case. The properties of elicited seizures, as well as the threshold for production of seizures, have been used with some success for detection of neurotoxicity. Several seizure models are discussed. It is concluded that both classes of neuronal challenge hold promise for future studies of neurotoxicity.

Acrylamides↗
PubMed1981

Acrylamide neurotoxicity: effects on far-field somatosensory evoked potentials in rats.

These experiments were designed to determine the sites of acrylamide induced damage in the specific ascending somatosensory system. Far-field somatosensory evoked potentials (SSEPs) were measured in adult rats given 400 ppm acrylamide in drinking water for 4, 8, or 16 days. Treated rats showed a statistically significant weight loss after 8 days of exposure and became visibly ataxic after about 12 days exposure. SSEPs were collected using modified techniques of Wiederholt and Iragui-Madoz [9] which enhance three far-field peaks arising from (I) the spinal posterior columns, (II) the posterior column nuclei and medial lemniscus, and (III) the thalamus and thalamo-cortical radiations. The three far-field peaks occur prior to the first cortical peak (P1). Tibial nerve stimulation voltage and frequency profiles revealed statistically significant alterations in all SSEP peaks after 16 days exposure. These findings indicate that damage may have occurred throughout the ascending somatosensory system including the spinal cord, dorsal column nuclei, medial lemniscus, thalamus, and sensory radiations.

Acrylamides↗
PubMedDate not supplied

Topical exposure of the eyes to the organophosphorus insecticide malathion: lack of visual effects.

Concern for toxicity following exposure to organophosphorus insecticides led us to investigate whether topical application of either malathion or malathion mixed in a protein bait as used for aerial spray applications could be toxic to the ocular/visual system. Adult male Long-Evans rats were either untreated or treated with malathion alone (two drops per day in each eye), bait alone (six drops per day in each eye) or malathion and bait (six drops per day in each eye). The dose levels of malathion alone and malathion and bait were chosen based on pilot work and provided approximately equivalent amounts of active ingredient. The rats were treated 5 days a week for 4 weeks. During the final week of treatment, the rats were implanted surgically with cranial recording electrodes overlying the visual projection area of the cerebral cortex. Visual pattern-evoked potentials (PEPs) were elicited with vertical sinusoidal gratings at three levels of stimulus spatial frequency (0. 08, 0.16 and 0.32 cycles per degree) and three levels of visual contrast (0.15, 0.30 and 0.60). After spectral analysis of the PEP waveforms, the amplitude and phase at the stimulus rate (F1) and the first harmonic (F2) were determined. Although F1 and F2 parameters were influenced significantly by manipulation of the stimulus parameters, no significant differences were observed that could be attributed to treatment with the test substances. In addition, an ophthalmological examination of the eyes and a light microscopic evaluation of ocular tissues, including retina and optic nerve, revealed no treatment-related lesions. The dose levels used in this study were high-approximately 84000 times the exposure per unit surface area expected from aerial spraying-and yet the visual function of the treated subjects was apparently normal. This study identified no significant toxicological concerns regarding direct ocular contact exposure to malathion.

Administration, Topical↗
PubMedDate not supplied

Effects of organophosphates on the visual system of rats.

The possibility that exposure to organophosphate insecticides can lead to ocular damage is suggested by Japanese studies from the 1960s and 1970s indicating that exposed humans developed chronic ocular degeneration, in addition to showing more commonly accepted effects of cholinesterase-inhibiting compounds. Other papers reported ocular lesions in laboratory animals treated with organophosphates. More recently, retinal degeneration following chronic organophosphate treatment has been reported to the Environmental Protection Agency by pesticide manufacturers in studies conducted in compliance with good laboratory practice regulations. Several factors, however, have prompted scepticism regarding organophosphate-induced ocular toxicity, including the widespread use of organophosphate compounds for both agricultural and ophthalmological practices without numerous additional reports of comparable ocular toxicity. We are developing a research program to address these issues involving electrophysiological, biochemical and histological investigations of rats treated with organophosphate insecticides. The research program is young, but early results are available. Notably, retinas from rats treated with a single subcutaneous injection of 100 mg kg-1 fenthion showed decreases in carbachol-stimulated release of inositol phosphate, an indicator of cholinergically-mediated intracellular second messenger systems. These effects persisted at least 56 days after fenthion administration. This could indicate several different toxicological actions, which are currently under investigation. It is concluded that the possible association between exposure to organophosphates and ocular toxicity cannot be dismissed, and that several important research issues need to be resolved.

Animals↗
PubMedDate not supplied

Stationary pattern adaptation and the early components in human visual evoked potentials.

Pattern-onset visual evoked potentials were elicited from humans by sinusoidal gratings of 0.5, 1, 2 and 4 cpd (cycles/degree) following adaptation to a blank field or one of the gratings. The wave forms recorded after blank field adaptation showed an early positive component, P0, which decreased in amplitude with spatial frequency, whereas the immediately succeeding negative component, N1, increased in amplitude with spatial frequency. P0 and N1 components of comparable size were recorded at 1 cpd. Stationary pattern adaptation to a grating of the same spatial frequency as the test grating significantly reduced N1 amplitude at 4, 2 and 1 cpd. The N1 component elicited at 4 cpd was attenuated in log-linear fashion as the spatial frequency of the adaptation grating increased. P0, on the other hand, was unaffected by stationary pattern adaptation at all combinations of test and adapting spatial frequencies, although P0 amplitude is known to be attenuated by adaptation to a drifting grating. Since N1, but not P0, was significantly attenuated following adaptation and testing at 1 cpd, it was concluded that the neurons generating these components are functionally distinct. The use of a common adaptation grating discounted the possibility that N1, but not P0, was affected due to a difference in the rates of retinal image modulation caused by eye movements made while viewing adaptation gratings of different spatial frequencies. The neurons generating N1 were adapted at a lower rate of retinal image modulation than that apparently required for adaptation of the neurons generating P0, which suggests a difference between these neurons in the rate of stimulus modulation necessary for activation.

Adaptation, Ocular↗
PubMedDate not supplied

Effect of perinatal monosodium glutamate administration on visual evoked potentials of juvenile and adult rats.

Administration of high doses of monosodium glutamate (MSG) to rats during the first postnatal week results in severe losses of retinal ganglion cells and interneurons in the retina. This study was conducted to determine what effect severe retinal damage would have upon the ontogeny of rat flash evoked potentials (FEPs) and the adult pattern reversal evoked potential (PREP). MSG (4 mg/g) or isotonic saline was administered to rat pups daily from postnatal day (PND) 2 until PND 9. FEPs were recorded following 2 stimulation frequencies from unanesthetized, unrestrained MSG treated and control rats on PND 15, PND 22, and PND 60 or older. PREPs were recorded from unanesthetized, restrained rats older than PND 60 from each treatment group. On PND 15, 9 of 12 control animals exhibited responses to light flashes, while only 4 of 13 MSG treated animals did so. All animals from both treatment groups exhibited FEPs on PND 22 and beyond. All FEP peak latencies were significantly increased in MSG treated animals with the magnitude of the effect being greater during development. Peak N1 amplitude was reduced in MSG treated animals by 50% or more at each age. Frequency x treatment interactions were observed on peak P2 and peak N3 latency, and a frequency x age x treatment interaction was observed on peak N3 amplitude. MSG treatment severely impaired the ability to generate PREPS. Only small responses to the pattern reversal stimulus could be detected and the normal PREP peaks could not be identified with confidence. Perinatal MSG treatment results in profound alterations in FEP ontogeny and the generation of PREPs.

Aging↗
PubMedDate not supplied

Rat and human visual-evoked potentials recorded under comparable conditions: a preliminary analysis to address the issue of predicting human neurotoxic effects from rat data.

Pattern-onset visual-evoked potentials (VEPs) were recorded from rats and humans in order to perform cross-species comparison of neuronal functional properties reflected by the early VEP components. The spatial frequency of a sinusoidal test grating was varied in Experiment 1. For both species, amplitude of the first positive VEP component was larger at low spatial frequency and decreased as spatial frequency increased. The immediately succeeding negative component was small at low spatial frequency and was of maximal amplitude at moderate spatial frequency. The effects of stationary pattern adaptation on these components were investigated in Experiment 2. Subjects viewed either a blank field or the test grating prior to recording VEPs. For both species, adaptation had no effect on the positive component but strongly attenuated the negative component. Experiment 3, in which only humans were tested, indicated that the negative component was of cortical origin. Only cortical neurons are known to be orientation selective, and the effect of adaptation diminished as the orientation difference between the adaptation and test gratings increased. These results suggest that the early positive and negative components arise from parallel visual pathways, and that the rat components may reflect visual processes qualitatively similar to those of humans.

Adaptation, Physiological↗
PubMedDate not supplied

Acute sulfolane exposure produces temperature-independent and dependent changes in visual evoked potentials.

Sulfolane (tetrahydrothiophene-1, 1-dioxide) is a commercially important solvent. This report describes the consequences of acute exposure to sulfolane upon the visual system, as measured using flash evoked potentials (FEPs) and pattern reversal evoked potentials (PREPs). A single injection of either 1/2 or 1/4, but not 1/8 the IP LD50 (1600 mg/kg) produced significant changes in both FEPs and PREPs which were apparent within 1 hour and lasted longer than 6 hours. Amplitudes of FEP peaks to the first of a pair of stimuli were generally increased compared to control, an effect which was not temperature-dependent. In addition, sulfolane produced an ambient temperature- and dose-dependent hypothermia. Sulfolane increased latencies of FEP and PREP peaks, but attenuating hypothermia eliminated the effect of sulfolane on latencies.

Animals↗
PubMedDate not supplied

Neurophysiological effects of 30 day chronic exposure to toluene in rats.

Long-Evans hooded rats were exposed to 1000 ppm toluene or 0 ppm toluene 6 hr/day, 5 days/week for 30 days. Following removal from the exposure conditions (18-26 hr) flash-evoked potentials were recorded to paired light flashes and pentylenetetrazol (PTZ) seizure properties were examined. No alterations were found in the response to the first flash, but alterations in the recoverability of the nervous system were demonstrated by significant latency shifts in the response to the second of the paired flashes, using first flash latencies as covariates. No significant alterations were found in PTZ seizures. The data indicated that at these exposure levels toluene produced a small but significant alteration in brain function, even after toluene had been completely metabolized.

Animals↗
PubMedDate not supplied

Trimethyltin reduces recurrent inhibition in rats.

Rats with electrodes chronically implanted in the perforant path for electrical stimulation, and dentate gyrus for recording were treated with a single oral administration of either saline, 5 mg/kg trimethyltin (TMT) or 6 mg/kg TMT. Recurrent inhibition was assessed by paired pulse activation of the perforant path input to the dentate gyrus. The measure of recurrent inhibition employed was the ratio of the population spike amplitudes of the responses to the first and second of the paired stimuli. Inhibition was assessed immediately before, and at 2, 24 and 120 hr following TMT. The results indicated a reduction in inhibition as early as 2 hr following treatment, suggesting that TMT-induced destruction of hippocampal pyramidal cells may be secondary to their over-activation from an uninhibited mossy fiber system.

Analysis of Variance↗
PubMedDate not supplied

Pattern reversal and flash evoked potentials following acute triethyltin exposure.

Until recently, pattern reversal visual evoked potentials (PREPs) had not been used to examine effects of neurotoxic agents, despite their clinical utility. Acute exposure to triethyltin (TET), which produces cerebral edema and myelin splitting, increased flash evoked potential (FEP) latencies in previous reports [17,18]. We recorded PREPs and FEPs in adult Long-Evans hooded rats before, and 24 hr after, exposure to 0, 4.5 or 6.0 mg/kg IP of TET bromide. Significant increases in latency and changes in amplitude of PREP peaks were found in the 6 mg/kg rats. FEP peak latency increases did not meet the criterion for statistical significance. Thus, under the conditions recorded, PREPs were better than FEPs as a measure of TET-induced neurotoxicity.

Animals↗