Age peculiarities of trace discharges of after-effect and of the activity of epileptogenic zone in the hippocamp of rabbits]

Seizure activity in the hippocamp has been studied on 6-10-, 16-20-day and adult rabbits. The pattern and thresholds of trace discharges of after-effect evoked by the electrical stimulation of the hippocamp were found to be similar in animals of all age groups. However, the amplitude of after-discharges significantly increased during the development of the brain. After the formation of penicillin epileptogenic zone in the hippocamp, EEG of all animals exhibited the identical types of focal interseizure discharges and electrographic correlates of seizures, yet the amplitude of epileptifiorm discharges on the EEG increased with age. Contralateral hippocamp was involved into the pathological process more easily in young rabbits than in adult ones.     

Age peculiarities of actin polymerization in calves]

Studies have been made on the developmental changes in the polymerization degree of unfractionated actin extracts from skeletal muscles of 3-8-month calf embryos and adult cattle. It was shown that during the development, the polymerization capacity of actin increases, the increase being accompanied by a significant rise in the molecular weight of the protein. The pattern of age changes in the degree of polymerization of actin is similar to that in the molecular weight of actomyosin. Differences in fractional composition of actin extracts from skeletal muscles at various stages of embryonic development were observed. These differences may be responsible for age peculiarities of actin polymerization and may be associated with the formation of contractile activity in ontogenesis.     

Effect of acupuncture on the activity of experimental epileptogenic foci in the hippocampus of rabbits

Experiments were performed on rabbits with electrochemotrodes implanted into the left and right dorsal hippocamp. The evidence was obtained for the first time as to the marked inhibitory effect of acupuncture on epileptogenic foci created by penicillin microinjections into the hippocamp. The most effective was stimulation of the Min-Men point. The antiepileptic effect was potentiated on combined stimulation of the Min-Men and Yao-Yan-Guan points. The efficacy of the procedure was significantly decreased on stimulation of the points of another acupunctural canal. The epileptiform activity was potentiated by affecting the knowingly inactive points. The antiepileptic effect of acupuncture was significantly reduced with an increase in the number of acupunctures. This might be connected with the development of tolerance to enkephalins by which the effect of acupuncture is most likely mediated.     

Effect of strophanthin and digoxin on the activity of an experimental epileptogenic focus in the frog hippocampus

It has been shown on frogs with epileptogenic focus induced by the injection of penicillin (1000 U in 0.4 ml) into the hippocamp that preinjection (or injection on the background of the functioning epileptogenic focus) of strophanthin (1.8 and 0.18 microgram/g) or digoxin (1.2 micrograms/g) into spinal lymphaticus sac led to a sharp increase in interparoxysmal epileptiform discharges and electrographic correlates of fits on the ECG. The influence of cardiac glycosides upon the epileptized cerebral neurons is thought to be associated with the capacity of these drugs to inhibit Na+, K+-ATPase of neurons and their axons resulting in the disturbance of cerebral mediator activity.     

Increase in the activity of an epileptogenic focus in frog hippocampus as a result of kynurenines and its reduction by serotonin]

In frogs with epileptogenic focus induced by injection of penicillin (1000 U in 0.4 microliter) into the primordial hippocampus it was shown that pretreatment with two kynurenines (quinolinic acid -- 0.1 microgram, and d,l-kynurenine -- 1 microgram) into the focus region and their injection into the functioning epileptogenic focus led to a sharp increase of the interparoxysmal epileptiform discharges and electrographic correlates of the fit on the EEG. Anthranilic acid (5 microgram) did not influence the activity of epileptogenic foci, and serotonin (1 microgram) and 5-methoxytryptamine (1 microgram) decreased it significantly. It is suggested that the effect of kynurenines on neurones in the epileptogenic foci may play a certain role in the pathogenesis of epilepsy.     

Decreased acetylcholinesterase activity in the area of epileptogenic foci created by met-enkephalin in the hippocampus of rats

Experiments on rats with electrochemotrodes implanted in the left and right hippocamp have shown that in epileptogenic foci created by microinjections of met-enkephalin or D-ala-2-met-enkephalin into the hippocamp, acetylcholinesterase activity (AChE) was diminished. It is assumed that reduction in AChE activity is an adaptive mechanism by which the excitability of hippocampal inhibitory basket cells, which are sensitive to acetylcholine, is increased.     

The effect of disconnecting the hippocampus from the septum on the activity of septal neurons]

Extracellular recording of neuronal activity was performed in the medial and lateral septal nuclei (MS and LS) in unanaesthetized rabbits after coagulation of septo-hippocampal connections. The MS neuronal activity had many pathological features. The LS activity was normal in every respect. Spontaneous activity, reactivity to sensory stimuli and main characteristics of responses to sensory stimuli were preserved in LS (and in a part of MS neurones). Sensory effects were augmented in intensity and duration, the number of neurones in LS with theta-bursts increased twofold, theta-bursts were more regular, than in control animals. These effects may be explained by an increase of ascending RF influences, which is supported by the fact of outstanding similarity between sensory and reticular effects in septal neurones after hippocampal disconnection. The number of units with inhibition of activity in response to sensory stimuli decreased, habituation of responses was absent. That means that hippocampal influences are necessary for the organization of inhibitory phenomena in the septum, and, above all, for processes of gradual habituation.     

The endocannabinoid system controls key epileptogenic circuits in the hippocampus

Balanced control of neuronal activity is central in maintaining function and viability of neuronal circuits. The endocannabinoid system tightly controls neuronal excitability. Here, we show that endocannabinoids directly target hippocampal glutamatergic neurons to provide protection against acute epileptiform seizures in mice. Functional CB1 cannabinoid receptors are present on glutamatergic terminals of the hippocampal formation, colocalizing with vesicular glutamate transporter 1 (VGluT1). Conditional deletion of the CB1 gene either in cortical glutamatergic neurons or in forebrain GABAergic neurons, as well as virally induced deletion of the CB1 gene in the hippocampus, demonstrate that the presence of CB1 receptors in glutamatergic hippocampal neurons is both necessary and sufficient to provide substantial endogenous protection against kainic acid (KA)-induced seizures. The direct endocannabinoid-mediated control of hippocampal glutamatergic neurotransmission may constitute a promising therapeutic target for the treatment of disorders associated with excessive excitatory neuronal activity.     

Study of the threshold dose of penicillin which induces an epileptogenic focus during ontogenesis in the rabbit]

A local application on the cortex surface of a very small drop of Ringer solution containing Penicillin was performed to establish the threshold dose required to elicit and epileptogenic focus and consequently the occuring latency of it. Threshold doses are small (20 - 60 International Units) and show a significant decrease during the maturation of the C.N.S. On the other hand latencies, whatever the animal's age, decrease fairly. The results are confronted to the various supposed modes of action of penicillin, modes which involve a dysfonctioning of the Na+ and K+ ionic pump.     

腺苷对家兔颈动脉化学感受器活动的影响

The response of single carotid chemoreceptor afferent fibers upon adenosine acting on the carotid body (CB) was examined in 39 urethan-anesthetized rabbits. Totally 73 units with spontaneous discharge were recorded in our experiment. The results were as follows: (1) Of 55 units, 51 showed an increase in discharge frequency from 0.76 +/- 0.10 to 1.53 +/- 0.23 imp/s. A few new units were recruited concomitantly in response to intracarotid injection of adenosine (10 micrograms/kg). (2) Adding adenosine in the doses of 0.5, 1.5, 10, 50 and 100 micrograms/kg to the perfusate passing through the isolated carotid sinus led to dose-dependent increase in the discharge from 0.51 +/- 0.06 to 0.58 +/- 0.07, 0.78 +/- 0.13, 0.96 +/- 0.15, 1.11 +/- 0.17, 1.34 +/- 0.21 and 1.38 +/- 0.18 imp/s, respectively (P less than 0.001, n = 9 units). (3) In other 9 units with spontaneous discharge rate of 1.30 +/- 0.40 imp/s, the activity was decreased to 0.56 +/- 0.19 imp/s (P less than 0.01) by intracarotid injection of dopamine (50 micrograms/kg). Intracarotid injection of adenosine to the CB pretreated with dopamine still activated the units with an increase in firing rate to 1.07 +/- 0.28 imp/s (P less than 0.01). However, the increment was less prominent as compared with that of adenosine administration before dopamine injection (P less than 0.001). From the results obtained, it is hypothesized that the exciting effect of adenosine on the CB chemoreceptor may be attributed to its action on the presynaptic component of the chemoreceptor complex in attenuating the release of inhibitory transmitter dopamine, and its direct stimulating action on the chemosensory nerve endings.     

The effect of etimizol on the excitability and spontaneous super-slow activity of the structures of the rabbit brain]

Spontaneous superslow electrical brain activity and its changes were studied in acute experiments on curarized rabbits after administration of etimysol in doses of 1.0, 1.5 and 2.5 mg/kg. The effect of the drug persisted for three hours. Two oscillation phases were recorded in the medial group of mesencephalic reticular nuclei and the lateral nucleus of the hypothalamus: a short positive phase and a prolonged negative one. In other brain structures only negative waves were recorded. A significant functional rearrangement of correlative connections of brain structures took place in 90 minutes after the drug administration. The factor analysis showed that the most subtle connections were preserved in the neocortex and the dorsal hippocampus.     

Neural mechanisms in cardiac arrhythmias associated with epileptogenic activity: the effect of phenobarbital in the cat

Sudden unexplained death accounts for 5-17% of mortality in epileptic persons; autonomic dysfunction is thought to be a contributing factor. This paper describes the effect of phenobarbital (PB) pretreatment (20 mg/kg, i.v.) one hour prior to pentylenetetrazol (PTZ) 10, 20, 50, 100, 200, and 2000 mg/kg, i.v. given at ten minute intervals on autonomic parameters in the cat. PB depressed heart rate, blood pressure, and postganglionic cardiac sympathetic neural discharge, but did not significantly alter vagal discharge. PB shifted the peak duration of interictal activity from a lower to a higher dose of PTZ without affecting the average duration across doses. PB also significantly diminished the increases in heart rate and blood pressure induced by PTZ but altered neither the occurrence of arrhythmias nor the changes in cardiac autonomic neural discharge. Thus, PB appears to prevent only some forms of autonomic dysfunction associated with epileptogenic activity in this model.     

Comparative study of the epileptogenic effect of kainic acid injected into the cerebral cortex, hippocampus and amygdala in adult cats chronically implanted

Intracerebral injection of kainic acid in cerebral cortex, hippocampus or amygdala in cats chronically implanted showed that: 1) Hippocampus and amygdala presented a greater sensitivity than the cerebral cortex, while hippocampus presented a greater sensitivity than the amygdala to the generation of an epileptic focus. 2) Comparison of latency, mean duration of afterdischarges, and the mean time period to obtain the peak intensity of the afterdischarge in the three cited structures, showed that mean latency of the first afterdischarge was significantly shorter in hippocampus and amygdala compared with the cerebral cortex. Moreover the mean time period to reach the peak intensity of the afterdischarge was again shorter in the subcortical structures. 3) The epileptic foci both in hippocampus and amygdala were blocked by CNQX and muscimol. 4) The behavioral changes depended on the intensity of the epileptic process. Tonic-clonic convulsions appeared only when the motor cerebral cortex was involved. Finally, 5) kainic acid injections in hippocampus and amygdala elicited an intense neuronal destruction and gliosis of these structures. We conclude that intracerebral injection of low doses of kainic acid in cats represent a good model to study focal epileptic thresholds in the CNS.     

Frequency potentiation in the neonatal rabbit hippocampus

The formation of properties of frequency potentiation in the entorhinal afferent pathway of the hippocampus was studied in unanesthetized rabbits aged from 1 to 15 days. In areas CA₁ and CA₃ of the dorsal hippocampus in newborn rabbits repetitive (1–20 Hz) electrical stimulation of the perforant path led to an increase in amplitude of the slow wave of the field potential by 20–100% compared with the control and to an increase in the probability of response discharges from the neurons from 0–0.5 in the control to 0.8–1.0 during tetanization. In rabbits aged 2–3 days potentiation was more marked at a frequency of 4–6 Hz, whereas depression of the responses developed rapidly to a higher frequency of stimulation. The frequency optimum of 4–15 Hz was established on the 5th day. Potentiation of the first component of the field potential was observed starting from the 8th–10th day of life. The experimental results show that the property of frequency potentiation in the cortical afferent connections of the hippocampus is found in rabbits actually at birth, and it acquires the adult form at the beginning of the second week of life.Brain Institute, Academy of Medical Sciences of the USSR, Moscow. Translated from Neirofiziologiya, Vol. 11, No. 6, pp. 533–539, November–December, 1979.