Biomedical subjects

R S Dyer

Publications and source records attributed to R S Dyer.

87 records · Page 5Linked to original sources

PubMedDate not supplied

A time-course study of trimethyltin induced neuropathology in rats.

The extent and time course of trimethyltin (TMT) induced lesions in the rat nervous system was studied. Adult Long-Evans rats were treated with a single dose of 6.0 mg TMT/kg b.w. and were sacrificed at 8 hours, 3, 15, 30 or 60 days following exposure. Histopathological examination of the brains revealed that neurons in the pyriform/entorhinal cortices and in the olfactory tubercle were extremely sensitive to TMT toxicity showing significant necrotic changes 3 days after exposure. Extensive neuronal loss and astrogliosis were observed 15 days after intoxication. In the hippocampal formation, the granule cells of fascia dentata showed early changes; however, evidence of toxic destruction in this area was not extensive and subsided considerably by the 3rd week of intoxication. On the other hand, destruction of the pyramidal neurons in Ammon's horn became more pronounced throughout the experimental period, resulting in extensive cell loss in this structure. It is interesting to note that the CA3 neurons in the anteromedial (septal) portion of the Ammon's horn appeared to be more vulnerable than those located more laterally (temporally), while the reverse pattern was observed for the CA1,2 neurons. Large mesencephalic trigeminal neurons in the brain stem also showed early chromatolytic changes. Since total normal morphology of these neurons was observed at later posttreatment time without apparent neuronal loss in these areas, total recovery of these nerve cells could be postulated.

Animals↗

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↗

PubMedDate not supplied

Trimethyltin induced pathology in sensory neurons.

Pathologic changes in the retina, inner ear, pyriform cortex, olfactory tubercle, and dorsal root ganglia as a result of trimethyltin (TMT) intoxication were investigated. Long-Evans rats were orally intubated with TMT chloride at a dose of 6.0 mg TMT/kg b.w. Swelling of the optic fiber layer and necrotic changes in the ganglion and inner nuclear layers were observed in the retina as early as 72 hours after intoxication. Large segments of the retina were devoid of ganglion cells at later posttreatment times. The inner ear was also found to be extremely vulnerable to the toxicity of TMT. Edematous swelling of the hair cells and vacuolar changes of the spiral ganglion cells in the Organ of Corti were observed 24 hours after TMT exposure. Extensive destruction of these structures was evident 15-30 days after intoxication. Small neurons in the olfactory cortex (pyriform cortex and olfactory tubercle) also degenerated rapidly after TMT exposure. Electron microscopy demonstrated lysosomal accumulation and vacuolar changes in these nerve cells. Extensive destruction of both the pyriform cortex and olfactory cortex was observed 15 days after exposure. Although no necrotic change was observed in the neurons of the dorsal root ganglia, electron microscopy revealed extensive accumulation of lysosomes and formation of myeloid bodies both in the neuronal bodies and dorsal root fibers. Vacuolar breakdown and dissolution of the Nissl substance were found in some neurons. Thirty days after treatment, hypertrophy and hyperplasia of the neuronal mitochondria were observed. Such a change was believed to represent a compensatory response by these organelles. These findings provide the first morphological evidence of neuronal damage in the sensory neurons of both the central and peripheral nervous system following acute TMT administration.

Animals↗

PubMedDate not supplied

Species and strain comparison of acute neurotoxic effects of trimethyltin in mice and rats.

Pathological changes in the central nervous system in two strains of mice (BALB/c and C57BL/6) and two strains of rats (Long Evans and Sprague Dawley) as a result of trimethyltin (TMT) intoxication were compared. Both strains of mice were administered with trimethyltin chloride at a dosage of 3.0 mg TMT-Cl/kg b.w. while both strains of rats were exposed to 7.5 mg TMT-Cl/kg b.w. Animals were sacrificed at the time of development of observable neurological signs (tremor, aggression): 2 days for both strains of mice, 3 days for Long Evans (LE) rats, and 5 days for Sprague Dawley (SD) rats. It was found that there were both species and strain differences in TMT toxicity. Despite being exposed to a lower dose of TMT and for a shorter duration of time, mice showed more prominent neurological signs and hippocampal lesions than rats. Among the two strains of rats studied, LE rats were more sensitive than SD rats to TMT toxicity. The regional sensitivity of the CNS between mice and rats was also different, with mice showing most lesions in the hippocampal fascia dentata and rats showing more prominent neuronal damages in the olfactory cortices and hippocampal Ammon's horn. Our present investigation provides the first species/strain comparison on lesion development as a result of TMT intoxication.

Animals↗

PubMedDate not supplied

Trimethyltin-induced changes in gross morphology of the hippocampus.

Acute exposure to trimethyltin (TMT) produces alterations in hippocampal morphology. The purpose of this study was to arrive at a simple method for quantitative assessment of the gross changes in morphology which could then be used as a correlate in studies of TMT toxicity. Adult Long-Evans male hooded rats were treated with a single dose of TMT chloride and sacrificed either (a) within 11 days; (b) following 30 days; or (c) 105 days following treatment. Among a variety of morphological measures explored, the easiest and most clearly dosage-related was length of the line of pyramidal cells, from CA1 through CA3c. TMT shortened this line in a dosage- and time-dependent manner. Loss of cells appeared to begin in CA3c and progress through CA3b and CA3a as a dosage and time since treatment increased. It was concluded that this measurement may provide a useful morphological correlate for physiological and behavioral studies of TMT toxicity.

Animals↗

PubMedDate not supplied

Trimethyltin impairs retention of a passive avoidance task.

Trimethyltin is a neurotoxic organometal which produces neuronal damage in several limbic regions including the hippocampus, amygdala and the pyriform cortex. One administration of trimethyltin (5, 6 or 7 mg/kg) twenty one days prior to passive avoidance conditioning produced an impairment of retention when animals were tested 24 hours after training. Rats treated with trimethyltin exhibited shorter step-through latencies and freezing durations during the retention test. It was observed that the three dosages of trimethyltin were equally effective in disrupting retention performance. There retention deficits were not secondary to alterations in footshock sensitivity. The data presented here indicate that acute trimethyltin administration disrupted learning and memory. The compound might be a useful tool for examining the role of the limbic system in associative processes.

Analysis of Variance↗

PubMedDate not supplied

Trimethyltin, a selective limbic system neurotoxicant, impairs radial-arm maze performance.

Rats were trained for fifteen sessions in an automated eight arm radial maze prior to treatment with 6 mg/kg trimethyltin chloride. This compound is a neurotoxicant which primarily damages the limbic system, in particular pyramidal cells in the CA3 region of the hippocampus. Following treatment the animals exhibited a marked and persistent impairment of maze performance characterized by decreased selection accuracy and an altered spatial pattern of responding within the maze. These results offered additional evidence that CA3 pyramidal neurons or their connections play an important, if not essential, role in radial-arm maze performance. It was suggested that trimethyltin might be a useful tool for elucidating the neural substrates of both radial maze performance and learning and memory processes.

Analysis of Variance↗

PubMedDate not supplied

Visual system dysfunction following acute trimethyltin exposure in rats.

Trimethyltin (TMT) has been shown to produce damage in the limbic system and several other brain areas. To date, damage to sensory systems has not been reported. The present study investigated the integrity of the visual system following acute exposure to TMT. Rats were chronically implanted with electrodes for recording the evoked response from either the visual cortex or optic tract following photic stimulation. Following recovery, the animals were exposed to either 0 (saline), 4, 5, 6, or 7 mg/kg trimethyltin chloride (TMT). Evoked potentials were averaged the peak-to-peak amplitudes and latencies were determined. The results indicated that exposure to TMT produced alterations in the visual evoked response. The pattern of changes suggested two effects, an alteration in retinal processing and an alteration in arousal. The manifestation of these changes was an increase in early peak latencies recorded from the visual cortex and the optic tract, a decreased amplitude recorded from the visual cortex and optic tract early peaks (all suggestive of retinal changes) and a decreased P3N3 amplitude and N3 latency recorded from the visual cortex (suggestive of increased arousal). The results demonstrate that TMT does produce alterations in sensory systems as well as in the limbic system.

Analysis of Variance↗

PubMedDate not supplied

Somatosensory dysfunction following acute trimethyltin exposure.

A variety of trimethyltin (TMT)-produced sensory and behavioral dysfunctions have been reported. In this study the functional integrity of the somatosensory system was evaluated. Animals were tested using three different measures prior to (day 0) and 1, 4, and 16 days following dosing with either 0 (saline) or 7 mg/kg TMT. The tests employed were: (1) hot-plate pain threshold: (2) dorsal caudal nerve response threshold and conduction velocity; and (3) the somatosensory evoked response (SER). In the hot-plate test, TMT treated animals took longer to lick the hind paws in response to the heat. No effects were seen in the nerve function evaluation (conduction velocity and threshold), although increased N1, P1, and P2 latencies and decreased N1P1 amplitude were seen in SER recordings. The fact that no peripheral nerve function effects were observed suggests that the hot-plate and SER findings were the result of central nervous system dysfunction.

Animals↗

PubMedDate not supplied

Increased seizure susceptibility following trimethyltin administration in rats.

Acute treatment with trimethyltin (TMT) produces a multitude of behavioral effects including spontaneous convulsions in some animals. The present study used several different experimental seizure models to investigate seizure susceptibility in TMT-treated rats. Rats surgically implanted with electrodes in the amygdala and treated with TMT kindled more rapidly than saline-treated controls. Similarly, rats implanted with electrodes in the dorsal hippocampus kindled more rapidly than controls. Although TMT did not alter the properties of hippocampal afterdischarges, the threshold for production of after discharges was increased in both hippocampal and amygdaloid kindled rats, probably due to cell loss. TMT also increased the sensitivity of rats to pentylenetetrazol, thus suggesting that the increased seizure susceptibility was not limited to the limbic system.

Animals↗

PubMedDate not supplied

Acute triethyltin exposure: effects on the visual evoked potential and hippocampal afterdischarge.

Acute administration of triethyltin (TET) produces a well-described sequence of pathological events characterized by intramyelinic vacuolation, edema, and histotoxic hypoxia. Recent behavioral studies have attempted to characterize the functional consequences of TET exposures. In this study, the effects of exposure on the visual evoked response (VER) and hippocampal afterdischarge (AD) were determined. Rats were administered either 0, 0.188, 0.375, 0.75, or 1.50 mg/kg TET bromide IP each day for 6 consecutive days. TET increased latencies of P1, N1, P2, N2, and N3 peaks of the VER. The increased latencies are consistent with delayed conduction produced by alterations in the myelin of the optic nerve. TET increased the frequency of spikes within ADs, increased the severity of postictal EEG depressions, and prolonged recovery of excitability following ADs. These effects may be partially explained as reflecting a generalized CNS depression.

Animals↗

PubMedDate not supplied

Triethyltin: ambient temperature alters visual system toxicity.

Previous studies have indicated that acute exposure to triethyltin (TET) increases latencies of the flash evoked response (VER) recorded from the rat cortex. TET also produces hypothermia, which may be modified by altering environmental (ambient) temperature. In this study, the role of ambient temperature in determining the effects of acute TET upon the VER was examined. Rats with chronically implanted electrodes were administered either TET (6 mg/kg) or saline, and maintained in either a warm (30 degree C) or cool (22 degrees C) environment for the next 7 hrs. VERs were recorded during this 7 hr period, and at regular intervals for the next 2 weeks. TET increased VER peak latencies. VER peak latencies recorded from animals exposed in a cool room gradually returned to pre-TET values. Latencies recorded from animals exposed to TET in a warm room remained elevated for a longer period of time, thus indicating a more severe impact of the TET exposure. This study indicates that toxicant-induced alterations in core temperature are potential determinants of other toxicant-induced effects.

Animals↗

PubMedDate not supplied

Physiological methods for assessment of Trimethyltin exposure.

Trimethyltin has been reported to produce morphological alterations in the brain which are primarily restricted to the limbic system. A variety of physiological measures of limbic system integrity are discussed in terms of their ability to detect TMT-induced dysfunction. In addition, several measures of sensory dysfunction are discussed. It is concluded that limbic system dysfunction induced by this compound is detected more efficiently by intrahippocampal evoked potentials than by more gross measures of dysfunction. It is also concluded that relying upon preliminary descriptions of pathological alterations to direct physiological studies may provide an incomplete description of neurotoxicity.

Animals↗

PubMedDate not supplied

The trimethyltin syndrome in rats.

Trimethyltin (TMT) chloride, administered to adult male Long-Evans hooded rats, produced a unique and distinctive behavioral syndrome consisting of spontaneous seizures, tail mutilation, vocalization and hyperreactivity. The LD50 for TMT was weight dependent; in large rats (e.g., 450 g), 7 mg/kg TMT produced significant weight loss and lethality, whereas in small rats (e.g., 250 g), 7 mg/kg produced neither weight loss nor lethality. TMT produced mild hypothermia and tremors. Results are discussed in comparison with kainic acid-induced morphological alterations and septal lesion-induced behavioral alterations. Histopathological evaluations of hippocampal tissue revealed cell loss that was largely confined to regio inferior pyramidal cells. TMT offers potential as a tool for investigations of limbic system structure and function.

Animals↗

PubMedDate not supplied

Trimethyltin-induced hyperactivity: time course and pattern.

Adult male Long-Evans rats were intubated with either 0, 5, 6 or 7 mg/kg trimethyltin chloride. Activity was measured for 1 hr in a figure-eight maze 2 hr after dosing (day 0) and again on days 4, 8, 16 and 32 after dosing. On days 49-51, activity was measured in a figure-eight maze over a 23-hr period. There were no differences in activity on the day of dosing, but on all subsequent test days the 7 mg/kg TMT animals were hyperactive. TMT also altered the spatial pattern of activity: activity was increased in the "figure-eight" portion of the maze but not in the blind alleys. ACtivity of the 7 mg/kg TMT animals was increased during all periods in the 23-hr test. Decreases in the length of the pyramidal cell line (CA1 to CA3c of the hippocampus) confirmed neuronal cell loss in TMT-dosed rats.

Animals↗