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1.
Unilateral intrahippocampal injection of tetanus toxin results in a chronic syndrome of intermittent epileptic seizures. During some of these seizures, rats develop a stereotypic, pathological motor behavior that indicates secondary generalization of epileptic activity. We report that secondary generalization was preceded by a 9-16 Hz oscillation of field potentials which was synchronized between the right and left dorsal hippocampi. The oscillation was associated with increased synchrony of population spike firing in right and left CA1 subregions which form the major output of the hippocampi. Cutting the ventral commissure abolished synchrony across the hippocampi and reduced the probability that the 9-16 Hz activity would be followed by secondary generalization. We concluded that a bilaterally synchronous 9-16 Hz hippocampal oscillation played a role in the secondary generalization of focal seizures in this chronic model of limbic epilepsy.  相似文献   

2.
The dentate gyrus is thought to be a key area in containing the spread of seizure discharges in temporal lobe epilepsy. We investigated whether it actively contributes to the transition to seizure in vivo using the tetanus toxin chronic experimental epilepsy. Brief epileptic discharges lasted <2 s in freely moving animals and were clearly distinguishable from spontaneous seizures that lasted tens of seconds. This suggested that the changes underpinning the transition to seizure started within the first few seconds of seizure onset. During this period, we found that the amplitude of dentate gyrus population spikes depressed initially, but from 1.1 s after seizure onset, they potentiated. The amplitude and number of CA3 population spikes paralleled the pattern found in the dentate gyrus. We used hippocampal slices to study dentate filtering in more detail. The perforant pathway was stimulated repetitively at the frequency of field postsynaptic potentials found during epileptic discharges in vivo. The amplitude of dentate gyrus population spikes decreased to a steady state in na?ve hippocampal slices. In hippocampal slices prepared from rats previously injected with tetanus toxin, population spike amplitude decreased transiently and then potentiated. We found that the biphasic profile and rate of potentiation of dentate population spikes in vivo can be reproduced in na?ve hippocampal slices by blocking GABA(B) receptors. We conclude that the filtering properties of the dentate gyrus are altered in the tetanus toxin model of epilepsy and propose how this contributes to the transition to seizure in our animals.  相似文献   

3.
The effects of tetanus toxin (TeNT) both in the spinal cord, in clinical tetanus, and in the brain, in experimental focal epilepsy, suggest disruption of inhibitory synapses. TeNT is a zinc protease with selectivity for Vesicle Associated Membrane Protein (VAMP; previously synaptobrevin), with a reported selectivity for VAMP2 in rats. We found spatially heterogeneous expression of VAMP1 and VAMP2 in the hippocampus. Inhibitory terminals in stratum pyramidale expressed significantly more VAMP1 than VAMP2, while glutamatergic terminals in stratum radiatum expressed significantly more VAMP2 than VAMP1. Intrahippocampal injection of TeNT at doses that induce epileptic foci cleaved both isoforms in tissue around the injection site. The cleavage was modest at 2 days after injection and more substantial and extensive at 8 and 16 days. Whole-cell recordings from CA1 pyramidal cells close to the injection site, made 8–16 days after injection, showed that TeNT decreases spontaneous EPSC frequency to 38 % of control and VAMP2 immunoreactive axon terminals to 37 %. In contrast, TeNT almost completely abolished both spontaneous and evoked IPSCs while decreasing VAMP1 axon terminals to 45 %. We conclude that due to the functional selectivity of the toxin to the relative sparing of excitatory synaptic transmission shifts the network to pathogenically excitable state causing epilepsy.  相似文献   

4.
Studies were conducted to characterize a chronic epileptic condition that follows recurrent seizures induced by intrahippocampal tetanus toxin injection in infancy. Wistar rat pups received a single injection of tetanus toxin in the right CA3 region on postnatal day 10. Animals were monitored for epileptiform activity by video electroencephalographic or visual observation during the following three to five days. Repeat evaluation six months later demonstrated interictal discharges in 79% (11 of 14) and electrographic seizures in 42% (six of 14) of adult rats with tetanus toxin-induced seizures in infancy. Five of the animals had interictal activity which occurred focally in either the left (n = 2) or right (n = 3) hippocampus. One animal had focal interictal activity independently in these regions and in the left and right cortical regions. The remaining five animals had interictal activity in the hippocampus and synchronously in the ipsilateral cortex or the contralateral hippocampus. Electrographic seizures were focal (nine of 14) or bilateral (five of 14) in onset. The behaviors that accompanied these seizures were quite variable. Clonic face and forelimb movements were observed in some animals. However, a significant portion of rats had electrographic seizures with no associated behavioral change. Timm staining was performed on hippocampal sections from experimental and control animals. There was a significantly greater Timm score (aberrant Timm granules) in the inner molecular layer of the dentate gyrus in tetanus toxin-treated rats than in control rats. Our findings suggest that intrahippocampal tetanus toxin injection in infant rats results in a chronic focal epilepsy that persists for at least six months and is associated with aberrant mossy fiber sprouting in the dentate gyrus. The model described here contributes significantly to the evidence for chronic effects of recurrent seizures in early life, and provides a model for investigation of the molecular and cellular events that contribute to the development of chronic epilepsy.  相似文献   

5.
Inhibition of the substantia nigra pars reticulata has been shown to suppress seizures in different animal models of epilepsy. The striatum is the main input of the substantia nigra pars reticulata. The aim of the present study was to examine the role of dopaminergic neurotransmission within the striatum in the control of absence seizures in a genetic model in the rat. Injections of mixed dopaminergic D1/D2 or of selective D1 or D2 agonists or antagonists in the dorsal parts of the striatum led to suppression of absence seizures associated with strong behavioral and electroencephalographic side-effects. When injected in the ventral part of the striatum (i.e. the nucleus accumbens core), all these agonists and antagonists respectively decreased and increased absence seizures without behavioral or electroencephalographic side-effects. Combined injections of low doses of a D1 and a D2 agonist in the core of the nucleus accumbens had an additive effect in absence seizures suppression. Furthermore, combined injections of low doses of a GABA(A) agonist and a N-methyl-D-aspartate antagonist in the substantia nigra also had cumulative effects in absence seizures suppression.These results show that dopamine neurotransmission in the core of the nucleus accumbens is critical in the control of absence seizures. The modulatory and additive effects on absence seizures of dopaminergic neurotransmission through both the D1 and D2 receptors in the core of the nucleus accumbens further suggest that ventral pathways of the basal ganglia system are involved in the modulation of absence seizures.  相似文献   

6.
Preparation of purified actomyosin-like protein (ALP) was isolated from the coarse fraction of rat brain mitochondria. The ALP preparation contained Mg(Ca)-ATPase activity, inhibited by 0.1% deoxycholate, together with acetylcholinesterase activity and contractility (superprecipitation reaction). The contraction of ALP and ATPase activity were considerably reduced by tetanus toxin. Inactivated toxin had no effect. The possible functional role of ALP in the maintenance and secretion of mediators by nerve endings is discussed.Laboratory of General Pathology of the Nervous System, Institute of Normal and Pathological Physiology, Academy of Medical Sciences of the USSR, Moscow. Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 78, No. 12, pp. 24–27, December, 1974.  相似文献   

7.
A purified preparation of tetanus toxin (TT) (80–800 MLD/mg protein) was shown to induce liberation of both endogenous and exogenous (labeled with14C) noradrenalin (NA) from isolated nerve endings (synaptosomes) of the rat brain. Within the range of concentrations studied TT does not inhibit secretion of NA evoked by depolarization of synaptosomes by different methods in vitro.Laboratory of General Pathology of the Nervous System, Institute of General Pathology and Pathological Physiology, Academy of Medical Sciences of the USSR, Moscow. Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 89, No. 2, pp. 148–150, February, 1980.  相似文献   

8.
The effect of tetanus toxin in the goldfish   总被引:2,自引:0,他引:2       下载免费PDF全文
1. The effects of tetanus toxin have been investigated both on central nervous and peripheral neuromuscular systems of goldfish.2. Tetanus toxin kills goldfish when administered in minute doses. The lethal effect is temperature dependent. Unlike mammals, in which tetanus toxin produces spastic paralysis and convulsions, the tetanus-intoxicated goldfish die with an apparently flaccid paralysis.3. Inhibition and excitation were investigated on the Mauthner cells of goldfish which had been paralysed with tetanus toxin for at least 24 hr, and which were subsequently kept alive for up to 3 days by perfusing the gills with oxygenated water. In such fish, antidromically and orthodromically excited Mauthner cells were quite normal, and there was no apparent effect on either the collateral inhibition or the crossed VIIIth nerve inhibition.4. Local injection of sublethal doses of tetanus toxin into the pectoral fin muscles produced local paralysis of the fin. Nerve-muscle preparations were isolated from such goldfish; in tetanus toxin-paralysed fins, the muscle no longer responded to stimulation of its nerve. The nerve compound action potential was still present and the muscle still responded vigorously to direct electrical stimulation.5. It is concluded that the major part of the lethal action of the toxin in the fish must be ascribed to a peripheral effect, the blocking of neuromuscular transmission. The inhibitory neuronal systems acting on the Mauthner cells of the goldfish, in apparent contrast to those acting on mammalian spinal neurones, are highly insensitive to tetanus toxin.  相似文献   

9.
It is known that injecting a minute dose of tetanus toxin into rat hippocampus leads to a chronic epileptic syndrome. Here we describe the development of secondary, 'mirror' epileptic foci in the hippocampus contralateral to a single injection of the toxin (12 mouse LD50). This was detected in slices in vitro prepared 6 to 56 days after injection, both as evoked after-discharges and as spontaneous synchronous bursts that were mainly restricted to subregions CA3b and c.  相似文献   

10.
Traumatic brain injury is a major risk of post-traumatic epilepsy in a large number of individuals of different age groups. Lots of research has been done to elucidate the mechanism of post-traumatic epileptogenesis but age-related vulnerability to develop traumatic seizures is still unknown. Therefore, in the present study investigations were carried out to characterize the electrobehavioral seizure manifestation and associated alterations in young and old epileptic groups. FeCl3 injection model was used to induce post-traumatic seizures as this model closely resembles human post-traumatic epilepsy. Synchronized video-EEG monitoring was performed to diagnose manifestation of seizures in young (4 months) and old (18 months) rats. Biochemical and ultrastructural studies were performed to determine the mechanism behind the altered age-related vulnerability for post-traumatic seizures. Our result shows that old rats were more vulnerable to post-traumatic epilepsy due to faster seizure spread and lower latency for generalization of electro-clinical seizure activity. The observed biochemical and microscopic alterations associated with old age positively correlate with the altered susceptibility to develop seizures in old epileptic groups.  相似文献   

11.
12.
The neuropathological effects of local injection of tetanus toxin (TT) into various structures of the brain were studied in experiments on rats. Definite neuropathological changes were observed in the animals, different from those found after injection of TT elsewhere. As a rule the action of TT in a given region of the brain was local. The experiments confirm the theory of generator mechanisms of neuropathological syndromes, according to which specific manifestations of the corresponding syndrome are determined by the location of a generator of pathologically enhanced excitation in a certain brain structure.Laboratory of General Pathology of the Nervous System, Institute of General Pathology and Pathological Physiology, Academy of Medical Sciences of the USSR, Moscow. (Presented by Academician of the Academy of Medical Sciences of the USSR A. M. Chernukh.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 87, No. 2, pp. 124–126, February, 1979.  相似文献   

13.
Purified tetanus toxin (TT), in experiments in vitro, was shown to affect neither the Na,K-ATPase activity of the synaptic membrane fraction of the rat cerebral cortex nor the inhibition of Na,K-ATPase activity produced by electrical stimulation of a suspension of synaptic membranes, nor the binding of GABA-3H by synaptosomes. TT and colchicine (1 mM) reduced the osmotic sensitivity of the nerve endings. Colchicine, in low concentrations (10–5 to 10–3 M), does not affect Mg- and Na,K-ATPase but, in higher concentrations (10–2 M), it inhibits the activity of both ATPases considerably.Laboratory of General Pathology of the Nervous System, Institute of General Pathology and Pathological Physiology, Academy of Sciences of the USSR, Moscow. Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 83, No. 2, pp. 139–142, February, 1977.  相似文献   

14.
Intravenous injections of superoxide dismutase into rats with amygdaline kindling mitigated spontaneous and electrostimulation-induced epileptic seizures and raised the thresholds of electric current for their elicitation; these seizures of reduced intensity were observed during 3 days following chronic (for 6 days) treatment with this enzyme. In contrast, superoxide dismutase injections had no effect on the convulsions induced by electric shock or corazole. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 120, N o 7, pp. 20–22, July, 1995 Presented by A. N. Klimov, Member of the Russian Academy of Medical Sciences  相似文献   

15.
Summary Experiments were performed on white rats, affected by ascending general tetanus. The general convulsions were provoked with great ease by applying stimulation to the extremity into which a lethal dose of tetanus toxin had been introduced. This phenomenon was not connected with increased excitability of exter- ad proprioceptors and cannot be explained by the functional changes of the synapses, which have an inhibiting effect on the motor cells of the anterior horns of the spinal cord. The data which were obtained allow us to conclude that the effect of tetanus toxin is not limited to the area of motoneurons but that it, likewise, spreads to the synaptic formations of other portions of the multineuronic reflex arcs.Presented by Active Member of the Acad. Med. Sci. USSR, V. N. Chernigovsky  相似文献   

16.
Summary Spread of the excitation along the spinal cord was studied in white rats in ascending general tetanus. The special feature of this phenomenon is that the excitation becomes generalized completely (in some cases only) on stimulating the limb into whichthe lethal dose of toxin had been injected. The clinical effect takes the form of a convulsive attack with characteristic features of spasticity. High division of the spinal cord had no appreciable effect on the phenomenon.The same effect was observed on stimulating the central ends of the cut dorsal roots on the side of the toxin injection.Synchronization of the bursts of excitation occurred in remote groups of motor neurons located in different segements of the cord.The part played by the various types of internuncial and motor neurons of the spinal cord is discussed. It is suggested that neurons functioning as dispatching stations may play a special part.Presented by Active Member of the AMN SSSR V. N. Chernigovskii  相似文献   

17.
The peripheral action of tetanus toxin   总被引:1,自引:0,他引:1  
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18.
19.
Summary Experiments were performed on white rats in which the sensory and motor roots were divided subdurally.Deafferentation of one limb failed to prevent the development of a local tetanus following the injection of small doses of toxin into the muscles.Lethal toxin doses injected into muscles of a deafferented limb while the humoral route of the toxin is blocked by antitetanus serum causes not only local but also general and fatal tetanus.With the humoral route again blocked in the same way, lethal doses of toxin injected into the muscles of a deafferented limb do not cause a general tetanus.In a deafferented injected limb, action potentials could be recorded from the sciatic nerve, but not from that of the deafferented limb. It is concluded that central mechanisms play a very important part in both local and general tetanus.(Presented by Active Member AMN SSSR V. N. Chernigovskii) Translated from Byulleten eksperimental noi biologii i meditsiny Vol. 49, No. 1, pp. 42–48, January, 1960  相似文献   

20.
Summary Comparison of the effects produced by tetanus toxin and proserine (neostigmine) demonstrated in experiments on cats that tetanus toxin was not a cholinesterase inhibitor. There exists a functional antagonism between the action of the tetanus toxin and that of proserine. At the same time, functional synergism was found to exist between the action of the toxin and that of d-paracurarine as evidenced by the fact that curare block developed more rapidly in the toxin-poisoned muscle than in the normal one. With increase of intoxication periods there was a drop in the action potential amplitude in the muscle, and curare block developed more rapidly. A characteristic response of the intoxicated muscle to indirect rhythmic stimulation with a fairly high frequency (pessimal for the normal muscle) was an increase in the action potential during the initial stimuli, and a relative maintenance of its value during the later stimuli.The results of this work permit a conclusion that tetanus toxin disturbs the neuromuscular transmission. The possible mechanisms of this effect are discussed. It is very likely that tetanus toxin influences the excretion of the mediator by the presynaptic apparatus.Presented by V. V. Parin, Active Member, Academy of Medical Sciences, USSR Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 58, No. 10, pp. 65–70, October, 1964  相似文献   

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