Structural bases of the induction of immune reactions in emotional stress

Immobilization stress in rats can provoke damages of the brain parenchymal vessels, which are most pronounced in the reticular formation of the midbrain. In this case the blood plasma and cells enter the brain and the blood elements of brain tissue enter the circulation. Some experimental animals exhibit the serum complement-fixing brain antibodies and specific reactions of basophils to brain antigens 14 days after exposure to stress. Most of the rats reveal immune reactions and neurosensitivity a month later. Some of them exhibit the autoantibodies to norepinephrine and serotonin. It is suggested that stress-induced brain vascular damages may play an important role in the mechanisms of immune reaction induction.     

Lactate dehydrogenase isoenzyme spectrum in various areas of the reticular formation of the brain in rats: the effect of emotional stress

The changes in lactate dehydrogenase (LDG) isoenzyme content in the various brain areas were studied in intact Wistar rats and upon immobilization stress. LDG fraction levels were compared to BP changes during immobilization. The proportion of "anaerobic" LDG fractions was higher and the proportion of "aerobic" fractions lower in the dorsal area of midbrain substantia reticularis than in medulla oblongata reticular formation. The changes in LDG fraction content related to BP alterations during immobilization were observed in dorsal and ventral areas of midbrain (but not medulla oblongata) substantia reticularis. The proportion of anaerobic LDG4 fraction in the dorsal area of midbrain substantia reticularis was higher in rats with hypertensive responses, than in hypotensive animals. The changes in LDG5 fraction content were opposite. In the ventral area of midbrain reticular formation BP reduction was accompanied by a significant rise in "anaerobic" and a decrease in "aerobic" LDG fraction levels. The data obtained indicate certain differences in the intensity of aerobic and anaerobic processes of carbohydrate degeneration in various areas of substantia reticularis in control rats, as well as the correlation of changes in energy metabolism in the brain with BP alterations during emotional stress.     

Neuroendocrine mechanisms of participation of the raphe nuclei in the development of hypertensive reactions in emotional stress

The experiments on cats and rabbits have studied electroencephalographic, endocrine and blood pressure responses to stress (5-hour immobilization with electrical foot shock) before and after coagulation of the midbrain nuclei raphe. Blood pressure and adrenal responses in advanced (4-hour) stress were elevated in intact animals, the responses attenuating after coagulation of the nuclei raphe. Background bioelectrical activity of the midbrain reticular formation and hypothalamus was found to be activated in the operated animals. Stress was followed by the reduction in bioelectrical changes of the above subcortical structures with the parallel development of "burst" activity in the dorsal hippocamp.     

Biogenic amines in the brain structures of rats from genetically diverse strains under stress]

The content was studied of biogenic amines and their metabolites (by the method of high-effective fluid chromatography electrochemical detection) in the reticular formation of the midbrain, locus coeruleus and sensorimotor cortex in the rats of Wistar and August lines, differing in the behaviour in the open field, in conditions of immobilization stress. The dependence was revealed of the biogenic amines level on the animals genotype and individual characteristics. Most probably, the level of biogenic amines metabolism in central brain structures determines the stability of the animals against emotional stress.     

Effects of pralidoxime applied locally into the midbrain reticular formation on the hippocampal theta rhythm induced by acetylcholinesterase inhibition

After local administration into the midbrain reticular formation of an acetylcholinesterase reactivator--Pralidoxime, a significant decrease of intensity of hippocampal theta rhythm induced by previous inhibition of acetylcholinesterase by DFP was observed already after 10 min. This result suggests that cholinergic structures are localized in midbrain reticular formation and that they play a role in the origin of hippocampal theta rhythm.     

Biogenic amines in brain structures of rats of different zoo-social rank during immobilization stress]

The content of monoamines and their metabolites in different parts of the brain: mesencephalic reticular formation, locus coeruleus, sensomotor cortex was studied by high-performance liquid chromatography in rats with different zoo-social position. Content of dopamine and serotonin in the brain structures studied was found to be different in dominants and subdominants. Maximal changes of monoamines under immobilization stress were observed in dominants.     

Damage to the hemato-encephalic barrier during one-time immobilization stress

Intravenous injection of trypan blue followed by treatment of the brain according to the Falc-Hillarp was used for morphological study of the blood-brain barrier in control rats and in animals exposed to the 6.5-hour stress. The density of the blood-brain barrier as regards the macromolecules in control animals was found to be liable to noticeable areal variations. The zones of primary increased barrier permeability were found near the basal surface of the brain. Prolonged single immobilization stress gave rise to destructive changes in the blood-brain barrier in the reticular formations of the midbrain and medulla oblongata. Besides, in control animals, there was a slight increase in permeability of the brain areas marked by the reduced barrier density.     

Quantitative and qualitative automatic evaluation of afterdischarges in the study of antiepileptic drugs

An automatic analysis of bioelectrical activity in some structures of the rabbit's brain was performed after i.v. administration of diazepam, phenytoin or phenobarbital. It was found that diazepam raised the ratio of fast activity in the afterdischarges pattern but paralelly decreased the total energy involved in the production of after-discharges in the cortex and midbrain reticular formation. Phenobarbital caused a significant shift in frequencies, increasing the ratio of slow activities (in the exception of hippocampus) and decreased the power spectra of afterdischarges in all structures (in the exception of midbrain reticular formation). Phenytoin, similarly to phenobarbital, decreased the ratio of fast activities. This effect was significant only in thalamus and midbrain reticular formation. At the same time it increased the total power of signal from hippocampus and midbrain reticular formation.     

Stress-induced activation of the immediate early gene Arc (activity-regulated cytoskeleton-associated protein) is restricted to telencephalic areas in the rat brain: relationship to c-fos mRNA

Arc is an effector immediate early gene whose expression is induced in situations of increased neuronal activity. However, there is no report on the influence of stress on Arc expression. Here, we compared the induction of both c-fos and Arc mRNAs in the brain of rats exposed to one of three different stressful situations: novel environment, forced swimming and immobilization. An absent or weak c-fos mRNA signal was observed in control rats, whereas those exposed to one of three stressors showed enhanced c-fos expression in a wide range of brain areas. Constitutive Arc expression was observed in some areas such as cortex, striatum, hippocampus, reticular thalamic nucleus and cerebellar cortex. In response to stressors, a strong induction of Arc was observed, but the pattern was different from that of c-fos. For instance, activation of Arc but not c-fos was observed in the nucleus accumbens after immobilization and in the hippocampus after novel environment. No Arc induction was observed in diencephalic and brainstem areas. The present data show that Arc has a neuroanatomically restricted pattern of induction in the brain after emotional stress. Telencephalic activation suggests that a more intense induction of synaptic plasticity is occurring in this area after exposure to emotional stressors.     

Asymmetry of the electroencephalographic manifestations of REM and slow-wave sleep in the cat

Studies were carried out on cats by bipolar electrodes implanted into symmetrical points of somatosensory cortical areas, caudate nuclei, hippocampus, lateral geniculate bodies, reticular formation of the midbrain after section of the half of midbrain tegmentum and commissural systems of the brain. Animals with sections usually have asymmetry of sleep EEG. The phenomenon is revealed of the coexistence of slow-wave and paradoxal sleep in different brain halves.     

Characteristics of memory and the functional organization of the hippocampo-reticulo-neocortical complex of the brain in the acute postoperative period

In tests on dogs, rabbits and rats, it has been established that in acute postoperative period, the time of memorizing of conditioned signals (light, tone and metronome) is reduced, the time of realization of conditioned reactions increases, the excitability and the bloodflow of the midbrain reticular formation and Mg-AtPhase activity of pons Varolii raise. In the hippocampus the excitability and local bloodflow lower and the activity of Ca-Mg-ATPhase is enhanced. In the frontal cortex these processes do not change. Functional interrelations of the brain structures in the acute postoperative period are characterized by the weakening of the activating influence of the reticular formation on the frontal cortex and an increase of its suppressive action on the dorsal hippocampus. It is suggested, that the discovered damages in the higher nervous activity are stipulated by the changes in neurochemical organization of the brain.     

Recovery of stress-induced increases in noradrenaline turnover is delayed in specific brain regions of old rats

Male Wistar rats at 2 and 12 months of age were sacrificed before, immediately following, and at 6 and 24 hours after a 3-hour immobilization stress period. Levels of noradrenaline (NA) and its major metabolite, 3-methoxy-4-hydroxyphenylethyleneglycol sulfate (MHPG-SO4), in eight brain regions and plasma corticosterone levels were fluorometrically determined. Immobilization stress caused significant increases of MHPG-SO4 levels in all brain regions examined and significant elevations in plasma corticosterone levels in both 2 and 12 month old rats. In 2 month old rats, the MHPG-SO4 levels in all brain regions returned to control levels within 6 hours after release from the stress. However, in 12 month old rats, the metabolite levels in the hypothalamus, amygdala, pons plus medulla oblongata (pons+med. obl .) and midbrain still remained at significantly increased levels at 6 and 24 hours after the stress. Moreover, in the amygdala of older rats, stress-induced decreases in NA levels persisted even 6 hours after stress. Plasma corticosterone levels also showed significant elevations at 6 and 24 hours after the stress only in 12 month old rats. These results suggest that brain NA metabolism during recovery periods from an acute exposure to a stressful situation is altered by the aging process in such a manner that NA neurons in the hypothalamus, amygdala, pons+med. obl . and midbrain in older rats remain activated by stressful stimuli for prolonged periods of time following release from stress.     

Role of the reticular formation of the midbrain in the process of formation of background activity of cortex neurons

In strict experimental conditions the basic activity of optic-cortex neurons in the rabbit was depressed after transverse section at the level of the rostral part of the reticular formation of the midbrain. Electrolytic destruction or functional blockage of the midbrain reticular formation (nucleus reticularis tegmenti) produces a decrease in frequency and magnitude in the grouping indexes of the cortex-neuron pulses that manifest the activity in these conditions. Destruction of specific nuclei in the optic pathway (those of the lateral geniculate body and the corpora bigemina) made no substantial change in the nature of the cortex-neuron pulses. Comparison of the parameters of pulsation activity of the same cortex neurons, as recorded before and after functional exclusion of the midbrain reticular formation, revealed that the increase in grouping of these pulses after the reticular formation was blocked induced changes in the intervals between groups of pulses, while the frequency of pulses within the groups remained constant. On the basis of the data obtained we may assume that the midbrain reticular formation plays an important role in generation of the background activity of cortex neurons, being a triggering mechanism that sets off a group of pulses. Distribution of pulses within the group is apparently due to the activity of cortex mechanisms only.A. A. Bogomolets Institute of Physiology, Academy of Sciences of the Ukrainian SSR, Kiev. Translated from Neirofiziologiya, Vol. 2, No. 1, pp. 43–51, January–February, 1970.     

Shifting of the brain stem physiological impedance after ovariectomy and oestradiol implantation in rabbits

Experiments were carried out on female rabbits with electrodes implanted chronically into the midbrain, dorsal hippocampus and the cerebral cortex. Physiological impedance of the brain stem, i.e. the lowest energy of trains of electric impulses stimulating the midbrain modulated through a feedback by the hippocampal theta rhythm and maintaining EEG arousal pattern, served as a measure of excitability of the brain stem reticular formation. After ovariectomy performed in 12 female rabbits, a rise in the brain stem physiological impedance was observed in relation to control measurements -- by 84.8%, on the average. In 8 ovariectomized female rabbits the physiological impedance decreased by 47.4% after subcutaneous implantation of oestradiol benzoate tablets. After removal of the implanted tablets the impedance increased by a mean value of 100.1% in all the female rabbits.     

Postnatal development of the scratch reflex in rabbits]

The development of the scratch reflex was studied in newborn (up to 2 months old) rabbits in norm and after elimination or activation of some parts of their nervous system (reticular formation, cerebellum, caudate nucleus, cerebral cortex, superior cervical sympathetic ganglia). The experiments with the section of the brain stem at the border between the medulla and the midbrain showed that in very young (5-10 days old) rabbits in norm the scratch reflex is controlled by the spinal cord with no influences of structures situated above the section's level. Later on the spinal mechanism of the scratch reflex becomes subject to supraspinal influences, among which in 2-3 weeks old animals facilitatory effects are predominant produced, in particular, by the reticular formation and the cerebellum, whereas in older age prevail inhibitory influences of the cerebral cortex, cerebellum, caudate nucleus and the sympathetic nervous system.     

Characteristics of heterochromatin of heterophase nuclei from interphase neurons of various brain structures selected for the nervous system excitability

Quantitative characteristics (the area and number of chromocenters) of the interphase C-heterochromatin in the nuclei of pyramidal neurons of the midbrain reticular formation, sensorimotor cortex, and hippocampus (CA3) of rat strains with different genetically determined excitability were studied in the normal state of the animals and after exposure to a short-term emotional pain stress. The results indicate a relationship between the excitability of the nervous system and structural-functional state of the neuronal interphase heterochromatin. The role of cytogenetic features of different brain structures in the CNS functioning and behavior and their relation with genetically determined excitability of the nervous system are discussed.     

Participation of angiotensin II in the establishment of negative emotional reactions

In waking rats and rabbits systemically injected angiotensin II was shown to participate predominantly in the mechanisms of negative emotional reactions. The effects of angiotensin II were observed at the behavioural level as well as at the neuronal one. Depending on the dose and the time of injection of angiotensin II and its specific antagonist saralasin they inhibited or facilitated elaboration and extinction of automatized conditioned active avoidance independently of arterial, pressure changes, the pain threshold being altered. Injection of angiotensin II abolished individual behavioural reactions of the animals in response to stress factors and increased their resistability to emotional stress. The negative emotional reactions were found to induce changes of chemosensitivity of neurones of the parafascicular complex of the medial thalamus and the midbrain reticular formation during microionophoretic application of angiotensin II. A supposition is made about the increase of angiotensin II brain synthesis under conditions of emotional stress.     

Brain catecholamines at the early stage of emotional stress

The blood pressure (BP) dynamics and catecholamine (CA) levels in the brain regions of August and Wistar rats were studied two hours after immobilization in order to elucidate the central neurochemical mechanisms leading to the destruction of BR self-regulation under emotional stress during the experiment. The BP level did not differ from the normal. The CA concentration in the hypothalamus, midbrain, isthmus rhombencephali and medulla oblongata underwent considerable changes. It is suggested that the mechanism of the CA changes in both strains of the rats exposed to stress is similar in the hypothalamus and medulla oblongata while both strains of the rats studied showed specificity in the activity of NA-synthesizing neurons of the isthmus rhombencephali and DA-synthesizing neurons of the midbrain that might be a cause of different resistance of cardiovascular functions during the later stage of immobilization.     

Metallothionein-I induction by stress in specific brain areas

The distribution of metallothionein-I (MT) in several areas of the brain and its induction by immobilization stress has been studied in the rat. MT content was highest in hippocampus and midbrain and lowest in frontal cortex and pons plus medulla oblongata. Immobilization stress for 18 hours (which was accompanied by food and water deprivation) significantly increased MT levels in the frontal cortex, pons plus medulla oblongata and hypothalamus, but not in midbrain and hippocampus. The effect of stress on MT levels was specific as food and water deprivation along had no significant effect on MT levels in any of the brain areas studied. The effect of stress on MT levels was independent of changes in cytosolic Zn content; this was generally unaffected by stress or food and water deprivation but decreased in pons plus medulla oblongata from stressed rats. The results suggest that MT is induced more significantly in the brain areas that are usually involved in the response of animals to stress.     

Taurine Levels in Discrete Brain Nuclei of Rats

Concentrations of taurine have been measured in 44 microdissected rat brain nuclei or areas. Taurine is ubiquitously present and distributed unevenly in the rat brain: the ratio of the highest (pyriform cortex) to lowest (midbrain reticular formation) concentrations is 4.7:1. High taurine levels were found in cerebral cortical areas, caudate-putamen, cerebellum, median eminence, and supraoptic nucleus. Acute pain stress reduced taurine levels in the hypothalamus and the lower brainstem nuclei but not in cortical areas. Increased locomotor and behavioral activities following a high dose of amphetamine elevated taurine concentrations significantly in the substantia nigra and locus ceruleus.