Progesterone: protective effects on the cat hippocampal neuronal damage due to acute global cerebral ischemia.

BACKGROUND: Barbiturates, benzodiazepines, and synthetic steroids having anesthetic properties, by enhancing the inhibitory GABAergic neurotransmission to the neuronal circuits of cerebral structures vulnerable to ischemia, reduce the damage induced by this condition. Some endogenous steroids resulting from progesterone (P4) biotransformation in the brain exert GABAergic effects, thus inhibiting neuronal excitability. Hence, P4 administration both before and after an experimentally induced ischemic episode may prevent or decrease the ischemic cerebral damage. METHODS: Ovariectomized adult cats were treated s.c. with either P4 (10 mg/kg/day) or corn oil during 7 days before and 7 days after being subjected to a period of acute global cerebral ischemia by 15 min of cardiorespiratory arrest followed by 4 min of reanimation. After 14 days of survival, animals were sacrificed and the brains perfused in situ and formalin-fixed for histological examination. RESULTS: Acute global cerebral ischemia resulted in a severe loss of neurons (54-85%), mainly in CA1 and CA2 subfields of oil-treated cats. Progesterone significantly reduced the neuronal loss in those areas (21-49%). CONCLUSIONS: Overall results suggest that progesterone exerts protective effects against the neuronal cerebral damage induced by acute global cerebral ischemia.

Effects of diazepam on fentanyl-induced epileptoid EEG activity and increase of multineuronal firing in limbic and mesencephalic brain structures.

Electroencephalographic and clinical signs of epileptoid activity have been associated with the administration of fentanyl during surgery in patients. These phenomena have been in turn related to changes in metabolic rate, oxygen consumption, and blood flow in specific brain structures both in humans and experimental animals. However, direct evidence showing changes in neuronal firing in specific brain regions during fentanyl-induced epileptoid activity has not been reported. Eight adult male cats with chronically implanted bipolar electrodes in the mesencephalic reticular formation, hippocampus, amygdala, and parieto-occipital cortex were included in the study. Different treatments, i.e., vehicle-fentanyl or diazepam-fentanyl, were administered to the experimental animals at 7-day intervals under neuromuscular blockade and assisted ventilation. Electroencephalographic (EEG) seizures, grouped and isolated spikes, and significant increases of multineuronal activity (MUA) were elicited by fentanyl, 50 micrograms/kg iv, in these brain structures. Both EEG and MUA changes reached their maximal values within 6 min of fentanyl administration, and then diminished as time elapsed. Diazepam, 100, 200, or 400 micrograms/kg, but not 50 micrograms/kg iv, significantly reduced or prevented the fentanyl-induced epileptoid EEG activity and MUA increases. The present results show that both fentanyl-induced epileptoid EEG activity as well as the concomitant increase in MUA of brain subcortical structures are part of the same epileptogenic phenomenon, mainly generated at limbic structures. In addition, the effects of diazepam against both epileptoid EEG activity and increase of MUA of brain subcortical structures support the use of benzodiazepines as premedicants for fentanyl anesthesia in order to prevent or to reduce epileptoid phenomena that can result from opioid administration during the anesthetic procedures.

Effects of propofol on alterations of multineuronal activity of limbic and mesencephalic structures and neurological deficit elicited by acute global cerebral ischemia.

The increment of GABAergic inhibitory activity, the reduction of metabolic rate and oxygen consumption induced by propofol on the neuronal components of brain structures, and its antioxidant potential have supported the possible beneficial effects of this drug against brain damage elicited by cerebral ischemia. Multineuronal activity (MUA) and EEG from mesencephalic reticular formation, hippocampus, and amygdala, and EEG from the parietooccipital cortex were recorded and analyzed during vehicle or propofol, 0.25 mg/kg/min i.v., administered during a 6 h period following a 10 min cardiorespiratory arrest and 2-4 min of reanimation in two groups of cats under neuromuscular blockade and assisted ventilation. This was continued daily during alertness for 8 days after cardiorespiratory arrest along with determining daily neurological deficit scores. Mean MUA frequency, progressively increasing in subcortical structures of untreated cats during the hours following cardiorespiratory arrest, was significantly lower in propofol treated cats. A significant reduction of MUA in the hippocampus was then observed in the untreated but not in the propofol treated cats, and in amygdala in both treated and untreated cats. Alterations of MUA were not observed in the mesencephalic reticular formation during alertness on the days after cardiorespiratory arrest. Significantly lower neurological deficit scores were recorded in propofol treated than in untreated cats the days after cardiorespiratory arrest. It can be concluded that propofol is capable of reducing both brain electrical activity alterations in specific brain structures, and neurological deficit elicited by complete global cerebral ischemia in cats. Inhibition of MUA from limbic and mesencephalic brain structures induced by propofol early after global cerebral ischemia could be related to these effects.

EEG signs of "relaxation behavior" during breast-feeding in a nursing woman.

The presence of electroencephalographic signs of "relaxation behavior"; i.e., groups of synchronic, 6-10 Hz, 100-150 microV EEG waves mainly appearing in parieto-occipital regions, have been investigated in a nursing woman during breast-feeding. EEG was recorded once a week from right and left frontal-central, central-parietal, parietal-temporal and parietal-occipital derivations of the mother during breast-feeding of her own child throughout 16 weeks of nursing (from the 4th to the 20th week after delivery). Groups of synchronic 6-10 Hz, 100-150 microV EEG waves were recorded in central-parietal and parietal-temporal derivations, 15-80 sec after starting of suckling of either breast. Proportions of this synchronic EEG activity ranged between 5 to 28% in the central-parietal and 6 to 22% in the parietal-temporal derivations, and significantly higher proportions were found in the right hemisphere. Similarities between EEG signs of "relaxation behavior" elicited by suckling in nursing cats and those elicited by suckling in a nursing woman lead to the possibility that the above described EEG phenomena are an expression of a functional state of the central nervous system which is a part of the integral response involved in the consummatory activity of nursing behavior in women.

Brain injury following cardiorespiratory arrest in cats. Effects of alphaxalone-alphadolone.

The effects of alphaxalone-alphadolone acetate (27.07 microM/kg-7.68 microM/kg) on neurologic injury following acute cerebral ischemia induced by an 8 min cardiorespiratory arrest (CRA) were investigated in cats through the analysis of neurological deficit scores and brain electrical activity; i.e., electroencephalogram (EEG) from parieto-occipital cortices and EEG and multiunit activity (MUA) from mesencephalic reticular formation (MRF). The CRA resulted from electrically induced cardiac arrest and stopping of mechanical ventilation in paralyzed cats which were successfully resuscitated within the immediate 4 min after the end of CRA. Two groups of cats were studied: I. Untreated, which received saline iv; II. Treated, which received alphaxalone-alphadolone acetate iv, 7-9 min after the end of CRA. Neuromuscular blockade and mechanical ventilation were maintained until 8 h following the CRA; then the cats were allowed to recover spontaneous respiratory activity. EEG phenomena were different in untreated and treated cats during this immediate post-arrest period. The former showed rhythmic bursts of fast (12-20 Hz) EEG activity at 1-2 sec intervals from 15-20 min until 3-4 h after the CRA, abundant spikes and delta-like waves. By contrast, administration of alphaxalone-alphadolone acetate resulted in burst suppression EEG pattern during 1 h. Progressive recovery of background EEG activity occurred afterwards. MUA from MRF disappeared during the CRA, however 6 h later the mean MUA frequency in untreated cats ranged between 32-46% and in treated cats 18-27% of their control mean frequencies during paradoxical sleep (100%). Daily electrographic records were performed in all the cats during quiet attentive behavior at each of the five days following the CRA. Significant differences were found in the frequency distributions of MUA from MRF (1st day, p less than 0.01; 5th day, p less than 0.01) as well as in the cortical EEG waves (1st day, p less than 0.01; 5th day, p less than 0.05) before and after the CRA in the untreated group. A wide dispersion of MUA values, and increased proportions of delta and theta-like waves and spindle bursts, besides a significantly high (p less than 0.001) number of spikes occurred in these EEG records the days following the CRA. The frequency distributions of MUA and EEG did not significantly differ before and after the CRA in the treated group; however, a significantly high (p less than 0.05) number of spikes was found in treated cats following the CRA.(ABSTRACT TRUNCATED AT 400 WORDS)

Serotonergic influences on EEG synchronization induced by milk drinking in the cat.

Milk drinking elicits electroencephalographic (EEG) synchronization in the parieto-occipital cortex of cats. This EEG change is a reliable correlate of the consummatory phenomena involved in "relaxation" behavior. The effect of varying serotonin brain levels by administering P-chlorophenylalanine (PCPA) or 5-hydroxytryptophan (5HTP) on this response was studied in 25 young cats. Single or repeated injections (4-8 days) of 50, 100 or 150 mg/kg of PCPA resulted in a dose related decrease in the duration of the EEG parieto-occipital synchronization during fixed periods of milk drinking. A single injection of 3, 10 or 30 mg/kg of 5HTP to chronic PCPA treated cats, restored the EEG parieto-occipital synchronization during milk drinking to control values. Moreover, administration of 5HTP to non-treated cats significantly increased the duration of EEG parieto-occipital synchronization during milk drinking. Our results suggest that brain serotonergic neurons are involved in the development of EEG synchronization during milk drinking.