Spindle evolution in normal and mentally retarded children: a review.

In neonates and infants, sleep-wake parameters indicate characteristic ontogenetic features. Sleep spindle activity also changes with maturation in terms of frequency, amplitude, and amount. For this reason, spindles are one of the useful indices of cerebral function in infants. The literature on the development of spindles in normal and mentally retarded children is reviewed.

Development of a computer program classifying rat sleep stages.

We developed a simple and precise program for the on-line judgement of the sleep stages of four rats simultaneously for an unlimited period, using a commercially available general purpose signal processor (NEC-Sanei 7T17; 32-bit, 5 MHz, 4 Mbyte, 1 Mbyte 1 floppy disc drive). EEG and EMG were recorded with an 8-channel polygraph (NEC-Sanei, System 380) through electrodes chronically implanted into the brain. The signals were A/D converted every ms and integrated for 2760 ms after full-wave rectification, and the subsequent 2240 ms was used for calculation and further analysis. All data were handled with this 5000 ms as the minimum unit. Then 3 sleep stages, i.e., waking, slow-wave sleep, and REM sleep, were determined by a template matching method from the relative amplitudes and durations of the integrated EEG, EMG and EMG surge data based on algorithms of standard visual amplitude analysis criteria for the sleep-stage classification. An agreement matrix was constructed between the data scored by the visual and by the automatic analysis, and the agreement value was satisfactory, although slight variability was seen in the REM sleep-stage determination. This result indicated that EEG and EMG data analysis is appropriate for researching the circadian rhythmic mechanism of the sleep-wake cycle.

Short-term, preweaning treatment with tetracycline affects physical development and behavior in rats.

Tetracycline (TC) was administered indirectly to rat pups through maternal milk, giving mothers diluted TC solutions as a single source of drinking water, during 13-16 days of postnatal age (PND) in Experiment 1. In Experiment 2, using rats of a different strain, TC dose and its application period were reduced from 0.5 mg/ml to 0.25 mg/ml and from PND 13-16 to PND 13-15, respectively. In Experiment 3, TC was administered directly to the pups via stomach intubation during PND 13-16. The effects of these short-term treatments were tested in adulthood. Brain weight decreased, although no abnormal changes were found histologically in the cerebral cortex. Immobility time in the forced swimming test was decreased more in the TC group as compared to the controls. These results suggest that even a small amount of TC could affect physiological development and behavior. In Experiment 4, mothers were given TC in their drinking water (0.5 mg/ml) for 1 to 5 days, beginning on PND 12. On each of the treatment days, measurements were made of the weight of brain and body, and of the concentration of TC in the brain and in gastric curd of offspring. The greater the TC intake by dams was, the more remarkable was the decrease in the brain weight of offspring. TC concentration of gastric curd was on the order of 1-3.5 micrograms/g curd.

Effect of histamine depletion on the circadian amplitude of the sleep-wakefulness cycle.

Behavioral states of rats were automatically classified with a newly developed computer program into three sleep stages (awake, slow-wave sleep and REM sleep) from continuous long-term EEG and EMG recordings for several circadian cycles under entrained circumstances (L:D = 12:12). Histamine was depleted by 100 mg/kg intraperitoneal administration of a specific inhibitor of its synthesis, alpha-fluoromethylhistidine, in the mid-light period. This treatment had no effect on the amount of each sleep stage in the total 24-h period or in the light period, but caused significant increases in slow-wave sleep and REM sleep in the dark period. Equivalent decrease in the awake stage during the dark period was also observed. As a result, histamine depletion decreased the light:dark ratio of slow-wave sleep. These findings suggest that decrease of the histamine content of the brain attenuated the circadian amplitude of sleep-wakefulness by suppressing the surge of wakefulness during the dark period. From these results, histamine is suggested to modulate the circadian amplitude of the sleep-wakefulness cycle.

Facilitative effects of maternal environmental enrichment on maze learning in rat offspring.

Pregnant rats were differentially reared in enriched (EC), impoverished (IC), and standard colony conditions (SC) through the pregnancy. Half of the male offspring were reared by their biological mothers and the remaining half were reared by foster-mothers. After weaning male offspring were tested in the Hebb-Williams maze apparatus. The effect of environment was significant for the total error scores; the EC group had less errors than the IC group. In a second experiment all male offspring (EC, SC and IC) were reared by foster-mothers. The effect of environment was significant for initial, repetitive, and total error scores. Further analysis revealed that the EC-SC and EC-IC differences were significant, whereas the IC-SC difference was not. Thus, the results obtained were the first to reveal that maternal environmental enrichment during pregnancy can exert a facilitatory influence on the postnatal maze learning abilities of the offspring.

Effects of alpha-fluoromethylhistidine on sleep-waking parameters in rats.

Effects of alpha-fluoromethylhistidine (FMH), an irreversible inhibitor of histidine decarboxylase, on the sleep-waking parameters were studied in rats for 24 hours. Intraperitoneal administration of FMH (100 mg/kg) at 11:30 hr resulted in a longer sleep latency compared with the control values. Hour-to-hour analyses revealed that wakefulness (W) time decreased (from 20:00 to 07:00 hr) and slow wave sleep (SS) time increased (from 19:00 to 06:00 hr) in the night. Paradoxical sleep (PS) time did not parallel the SS changes; it was increased significantly from 07:00 to 11:00 hr in the next morning. The influence of FMH seemed to be divided into direct, immediate action (increase of W) and late, prolonged action (decrease of W), and the results obtained support the histamine arousal hypothesis.

Cyclic variation of integrated spindle components during nocturnal sleep in mentally retarded children.

The cyclic variation of the integrated spindle component in 77 mentally retarded children (from 3 months to 12 years of age) was studied throughout nocturnal sleep. In 31 out of 77 subjects high integrated spindle rhythm power was noted in the sleep EEG. In 24 subjects, low integrated spindle rhythm power was found, and in the remaining 22 subjects no integrated spindle rhythm power was noted throughout nocturnal sleep. There was a significant increase in abnormal clinical EEGs in subjects with no spindle rhythm power as compared to those with high and low spindle rhythm powers. A significant decrease in DQ was found in the subjects with no spindle rhythm power as compared to those with high and low spindle rhythm powers.

Respiratory pauses and apnea during nocturnal sleep in mentally retarded infants.

Respiratory pauses (ResP), apnea (Ap) and periodic respiration (PerR) observed in 42 mentally retarded infants (from 9 to 50 weeks of age post term) were studied throughout nocturnal sleep. All subjects had ResP in the recordings. The range of ResP rates was 4.1-42.1/h, and the mean was 13.5/h. Ap occurred in 22 out of 42 subjects. The range of Ap occurrence (10-15 sec duration) among subjects was 1-10, with a mean of 4.1. Moreover, in 4 out of 22 subjects, Aps of greater than 15 sec duration were seen. In 30 out of 42 subjects, PerR occurred. The range of occurrence of PerR among subjects was 1-35, and the mean was 9.6.

Correlation between integrated delta and spindle components during nocturnal sleep in mentally retarded children.

The correlation between the integrated delta and spindle components in 81 mentally retarded children (from 3 months to 12 years of age) was studied throughout nocturnal sleep. In 57 (70%, Group A) out of 81 subjects, periodic changes of delta and spindle rhythm powers were noted in the sleep EEG. In 17 subjects (21%, Group B), delta and no-spindle rhythm powers were found, and in the remaining 7 (9%, Group C) no-delta and no-spindle rhythm powers were found throughout nocturnal sleep. A significant increase in abnormal clinical EEGs was found in groups B and C as compared to group A. A significant decrease in DQ was found in groups B and C as compared to group A. A significant decrease in DQ was also found in group C as compared to group B.

Delta and spindle components in compressed spectral array during nocturnal sleep in infants with congenital cerebral malformation.

The correlation between the delta and spindle components in compressed spectral array in 18 infants with congenital cerebral malformation (from 4 months to 4 years of age) was studied throughout nocturnal sleep. In 7 (39%, Group A) out of 18 subjects, periodic changes of delta and spindle rhythm powers were noted in the sleep EEG. In 5 subjects (28%, Group B), delta but not spindle rhythm powers were found, and in the remaining 6 subjects (33%, Group C) neither delta nor spindle rhythm powers were found throughout nocturnal sleep. A significant decrease in the developmental quotient was found in group C as compared with group A.

Nocturnal sleep in infants with congenital cerebral malformation.

Sleep EEG patterns in 17 infants with cerebral malformations (4 months to 4 years of age) were studied throughout nocturnal sleep and the following results were obtained. Seven cases evidenced normal sleep/wakefulness EEG patterns that could be classified into 6 stages. Ten cases showed abnormal sleep EEG patterns as follows: absence of sleep spindles (n = 7) which included cases of absence of EEG patterns characteristic of wakefulness, NREM sleep and REM sleep (n = 5), no characteristic EEG patterns of stages 1-4 (n = 1) and stages W, 1, 2 and REM (n = 1) and the remaining cases with absence of spindles (n = 1), and spindles with an extremely low incidence (n = 2). Short sleep and long awaking times, and no delta rhythmicity during the night, were noted in 5 out of 17 subjects. A significant decrease of DQ was found in subjects with indistinguishable stages including stages W, 1, 2 and REM, as compared with those patients whose stages were all distinguishable.

[Neuromuscular blockade following high-dose vecuronium administration].

To determine the onset time, duration of action and recovery time of high-dose vecuronium, 70 patients were assigned to receive either 100, 150, 200 or 300 micrograms.kg-1 of vecuronium for muscle relaxation during elective surgery. Neuromuscular blockade was continuously quantitated by recording the EMG response to stimulation of the ulnar nerve. The onset time from the time of vecuronium administration to maximum blockade decreased from 4.6 +/- 1.1 to 2.4 +/- 0.5 min when the vecuronium doses increased from 100 to 300 micrograms.kg-1. Significant differences were observed in the onset time between the 100 micrograms.kg-1 dose and the other dose groups. Endotracheal intubating conditions were excellent in all patients except 3 in the 100 micrograms.kg-1 dose group. The duration of action from the time of injection to 25% recovery increased from 32 +/- 9 to 138 +/- 48 min in a dose dependent manner. The duration of action after increment doses of 40 or 50 micrograms.kg-1 up to 25% recovery of T1 did not vary significantly within the same dose group. With an initial dose of 150 micrograms.kg-1 and subsequent increment doses of 50 micrograms.kg-1 or less, the duration of action remained constant. The recovery time from 25 to 75% recovery was within 11 minutes when antagonists were administered. High-dose vecuronium may, therefore, be a useful alternative to SCC, when a rapid onset is required and to pancuronium, when a rapid recovery from neuromuscular blockade is requested.

[The effects of ONO 3708, a new thromboxane receptor antagonist, on cardiovascular response during the early phases of endotoxin shock in anesthetized dogs].

The effects of ONO 3708, a new thromboxane A2 receptor antagonist, on cardiovascular and airway responses, at an early phase during endotoxin shock were investigated in anesthetized dogs. The i.v. infusion (1mg.kg-1) of E.coli endotoxin caused an increase in mean pulmonary artery pressure (MPAP) from 9.9 +/- 1.0 to 19.1 +/- 2.3 mmHg at 5 min, and at 15 min after infusion, elevated MPAP returned toward the control level. Pretreatment with ONO 3708 abolished these effects of endotoxin on pulmonary artery pressure at an early phase. The change in airway pressure reached a maximum of 14.4 +/- 1.7 cmH2O from 10.0 +/- 1.9 at 5 min, followed by a gradual decline toward a baseline value at 30 min in the control group. ONO 3708 significantly attenuated increase in airway pressure induced by E. coli endotoxin. But pretreatment with ONO 3708 could not prevent decrease in systemic arterial pressure and cardiac output induced by endotoxin. These results suggest that role of thromboxane A2 on the cardiovascular response during endotoxin shock is played only on pulmonary vascular changes, and ONO 3708 has a beneficial effect at least during the early phase of endotoxin shock.