Veselinka Šušić

“Recovery” function of sleep: Effects of purified human interleukin-1 on the sleep and febrile response of cats

From cats prepared for chronic pollygraphic recording of sleep patterns, records were obtained for 8 hr, after (1) intracerebroventricular (i.c.v.) injection of artificial cerebrospinal fluid (aCSF), day 1; (2) i.c.v. injection of interleukin-1 (Il-1), day 2; and (3) injection of aCSF, day 3. Three doses of Il-1 were tested. The dose of 40 nmol totally inhibited sleep, whereas the dose of 10 nmol slightly prolonged sleep. The dose of 20 nmol of Il-1 elicited sleep and a body temperature increase. Total sleep (TS) time was significantly increased, due mainly to the significant increase in non-REM (NREM) sleep as compared to control day 1. REM sleep was also increased, but this increase did not reach statistical significance. Wakefulness (W) was significantly reduced. At this time cats were febrile. On day 3, a further significant increase in TS occurred. NREM was significantly increased compared with day 1, whereas the increase in REM sleep was significant compared to both day 1 and day 2. At this time body temperature was normal. The increase in REM sleep on days 2 and 3 resulted entirely from the significant increase in the number of REM periods. The results show that Il-1 at a dose of 20 nmol has sleep-promoting effects on NREM and REM sleep concomitant with pyrogenic effects. These two responses differed in their time courses and were not correlated (correlation coefficients were all nonsignificant).

Sleep patterns in the owl Strix aluco.

Abstract In two owls the occurrence of paradoxical sleep was tested both behaviorally and electrographically. The waking and sleeping states of the owl can be clearly distinguished. Sleep consisted of two phases: a phase covering most of the sleep which is characterized by motionless posture, slow high-voltage EEG waves, reduced EMG activity of the neck muscles compared with the waking EMG, tonic bradycardia, reduced respiration rate and absence of eye movements; a phase occurring periodically, which is characterized by motionless posture, complete eyelid closure, absence of eye movements, presence of tonic EMG activity and by low voltage fast EEG pattern. Occasionally, this phase of sleep was associated with cardiac irregularities, respiratory apnea and gross body twitches. Thus this phase of sleep was considered to be analogous to the paradoxical sleep of mammals.

Sleep patterns in the Mongolian gerbil, Meriones unguiculatus

Sleep patterns were studied in Mongolian gerbils and normative values were derived from 48 hour recordings, during a 24-hr light-dark cycle (LD 12:12). Behavioral and electrographic observations confirmed the existence of well defined sleep states: slow-wave sleep (SWS) and paradoxical sleep (PS). During the light period, sleep occupied slightly more than half of the 12 hour period, 57.13 +/- 0.002% out of which 49.64 +/- 0.007% was occupied by SWS and 8.07 +/- 0.007% by PS. There were 23 +/- 0.01 episodes of PS with a mean duration of 2.32 +/- 0.01 min. During the dark period, sleep occupied slightly less than half of the recording time (51.75 +/- 0.01%). They spent 41.62 +/- 0.006% in SWS and 10.12 +/- 0.02% in PS. The number of PS episodes was 32 +/- 0 with a mean duration of 2.28 +/- 0.01 min. Sleep cycle duration was 7.80 +/- 3.76 min. The ratio day/night sleep was 1.17 +/- 0.002 min. We found that the gerbil in captivity, unlike most rodents that are nocturnal, is a crepuscular animal, being more active at the transitions between light and dark.

Potentiation of metaphit-induced audiogenic seizures by REM sleep deprivation in rats.

The possibility that REM sleep deprivation (REMD) induced increased susceptibility of rats to the convulsive effects of metaphit was investigated. Metaphit-induced audiogenic seizures were studied in three groups of animals: 1) caged controls; 2) large platform animals; and 3) small platform, REMD animals. After 48 h of confinement to their environments the rats from all three groups were injected with metaphit (10 mg kg-1, IP) and the procedures continued for the next 24 h. Immediately after removal from platforms and at 3-h intervals thereafter all rats were individually subjected to intense sound stimulation. Convulsive responses were recorded and analyzed with respect to incidence, intensity, and duration. The REMD rats were found to be more sensitive to the convulsive effects of metaphit compared to nondeprived rats. This was manifested in significantly shorter latencies to seizures, and significantly higher incidence, severity, and duration of seizures, especially of the most severe seizure component-tonic extensor convulsion. Inducing rats to convulse while they were being REM sleep deprived eliminated the REM sleep rebound observed in REMD rats that did not convulse. The occurrence of spontaneous EEG seizures during the undisturbed recovery period reduced REM sleep rebound. The results demonstrate a reciprocal relation between seizure behavior and REM sleep.

Electrographic and behavioural correlations of the rest-activity cycle in the sea turtle, Caretta caretta L. (Chelonia)

Behavioural and electrographic (EEG, EOG, EMG, EKG) observations were carried out during the activity-inactivity cycle of the sea turtle, Caretta caretta L. Observations were made on turtles kept in a tank with flowing sea water and under natural lighting. There were no clearcut changes in the amount of activity associated with the dark-light phase, although the peak of activity occurred in the early afternoon hours. During periods of behavioural inactivity, EEG changes were minimum and were not accompanied by consistent changes in the EMG of the neck muscles. Eye movements were absent at that time. Although much information is lacking, we tentatively conclude that the sea turtle does not exhibit signs of sleep, but alternates between states of activity and inactivity that are simultaneous with a non-altered level of responsiveness. Such association of low but responsive activity might be of survival value.

Inhibition of the Neuronal Nitric Oxide Synthase Potentiates Homocysteine Thiolactone- Induced Seizures in Adult Rats

Nitric oxide (NO), one of the gaseous neurotransmitters, is produced in reaction catalyzed by family of NO synthases (NOS). The involvement of neuronal NOS (nNOS) in seizures induced by homocysteine thiolactone has not been studied. Therefore, the aim of this study was to determine the effects of 7-nitroindazole, a selective nNOS inhibitor, on behavioral manifestations of homocysteine - induced seizures in adult rats. Adult male Wistar albino rats were treated with 7-nitroindazole (25, 50 and 75 mg/kg, i.p.) 30 min before injection of subconvulsive dose of homocysteine (D,L homocysteine thiolactone 5.5 mmol/kg, i.p.). Convulsive behavior was assessed during 90 min upon homocysteine administration by the following parameters: seizure incidence, duration of latency, number of seizure episodes per rat and their severity. Severity of seizures was evaluated using a descriptive scale graded from 0 to 4. It was shown that 7-nitroindazole increased seizure incidence, shortened latency time to first seizure, increased number of seizure episodes per rat and increased severity of seizures induced by homocysteine in rats. 7- nitroindazole in dose of 25 mg/kg led to a statistically significant increase in the seizure incidence and number of seizure episodes per rat, while doses of 50 and 75 mg/kg significantly increased severity of homocysteine-induced seizures. It could be concluded that inhibition of nNOS by 7-nitroindazole potentiates seizures induced by homocysteine in rats.

Paradoxical sleep deprivation: effects on brain energy metabolism.

A study was made of brain nucleotides and glycolytic intermediates in paradoxical sleep (PS)-deprived and recovery-sleeping rats. It was observed that PS deprivation of 24 h produced a fall in glucose, glucose 6-phosphate and pyruvate in cerebral frontal lobes. After three hours of recovery sleep all values returned toward their predeprivational levels. In cerebellar hemispheres ATP was increased, while glucose 6-phosphate and pyruvate were decreased. After three hours of recovery sleep, glucose 6-phosphate was increased and pyruvate decreased, indicating restoration of glycogen and creatine phosphate respectively.

Influence of NR2B-Selective NMDA Antagonist on Lindane-Induced Seizures in Rats

Ifenprodil is a novel NMDA receptor antagonist that selectively inhibits receptors containing the NR2B subunit. Lindane, a widely used pesticide and scabicide, evokes seizures mainly through the blockade of the γ-aminobutyric acid type A receptor complex. The aim of this study was to determine the effects of ifenprodil on the behavioral and electroencephalographic (EEG) manifestations of seizures in lindane-treated rats. Adult male Wistar rats with three electrodes implanted into the skull were treated intraperitoneally (i.p.) with lindane 8 mg/kg and observed for seizure behavior and EEG during the next 30 min. Seizure behavior was assessed by incidence, severity (determined by a descriptive rating scale ranging from 0 to 4) and duration of latency. Increasing doses of ifenprodil (5, 10, 20 mg/kg, i.p.) or vehicle were injected 30 min prior to lindane administration. Ifenprodil decreased the incidence and severity of lindane seizures and prolonged the latency to seizures in a dose-dependent manner. 20 mg/kg of ifenprodil significantly de- creased the incidence (p < 0.05) and severity (p < 0.05) of seizures when compared to the vehicle treatment. Latency to seizures was significantly prolonged by 10 and 20 mg/kg of ifenprodil. The estimated ED50 value of ifenprodil was 15.53 (5.48–15.20) mg/kg. The lindane-induced bursts of spiking activity in EEG were not completely suppressed by the applied doses of ifenprodil. These results indicate that ifenprodil alleviates behavioral seizures and modifies EEG characteristics of lindane seizures in rats, thus showing the involvement of NMDA receptors containing the NR2B subunit in the mechanisms of lindane convulsions.

APH, an N-methyl-D-aspartate receptor antagonist, blocks the metaphit-induced audiogenic seizures in rats

The effect of the competitive antagonist of the N-methyl-D-aspartate (NMDA) receptor, (+/-)2-amino-7-phosphonoheptanoic acid (APH) on electrocorticographic (ECoG) activity and behavior was studied in the model of epilepsy induced by systemic application of metaphit (1-(1-(3-isothiocyanatophenyl)-cyclohexyl)-piperidine). Male Wistar rats were injected with metaphit intraperitoneally (10 mg/kg, i.p.), and exposed to intense audio stimulation (electric bell generating 100 +/- 3 dB at animal level for 60 s) 1 h after administration and at 1-h intervals thereafter. ECoG tracings showed appearance of paroxysmal activity in form of spikes, spike-wave complexes and ECoG seizures. Audiogenic seizures consisted of wild running followed by clonic and tonic convulsions. Each behavioral seizure response had a characteristic ECoG correlate. The incidence and severity of seizures increased with time, reaching a peak 8-12 h after metaphit administration, and then gradually decreased until 31 h, when no animal responded to sound stimulation. APH was injected intracerebroventricularly (0.005, 0.01, 0.02, 0.03 and 0.05 mumol icv in 5 microL of sterile saline) after the 8th hour of audiogenic testing (AGS). APH inhibited seizures in a dose-dependent manner. The minimum dose which blocked seizures in all animals was 0.03 mumol. However, ECoG signs of seizure susceptibility were not suppressed by APH. After varying periods of time, behavioral seizures reappeared. It seems that APH blocks epileptiform propagation, but has less influence on the epileptogenic activity caused by metaphit.

Delta-Sleep-Inducing Peptide Potentiates Anticonvulsive Activity of Valproate against Metaphit-Provoked Audiogenic Seizure in Rats

The effect of delta-sleep-inducing peptide (DSIP) on the anticonvulsive activity of a nonprotective valproate (VPA) dose in a metaphit model of generalized, reflex audiogenic seizures in adult Wistar rats was studied. The animals that received metaphit (10 mg/kg) were exposed to audiogenic stimulation (100 ± 3 dB, 60 s) at hourly intervals. Metaphit-treated rats displaying seizures in 8 previous tests were i.p. injected with VPA (50 mg/kg) or DSIP (1.0 mg/kg) or their combination. Latency to seizure was behaviorally assessed. The EEGs and power spectra were recorded and analyzed. Neurotoxicity was evaluated by the chimney test. DSIP or VPA alone expressed no significant effect on the latency duration, but their combination significantly prolonged latency to seizure during 6 h after injection, while inducing no significant motor impairment. Neither the applied drugs nor their combination abolished metaphit-provoked EEG epileptiform activity. The results show that DSIP potentiated anticonvulsive effects of a nonprotective VPA dose in a metaphit model of audiogenic seizures without influencing its neurotoxicity.