scholarly journals Investigation of the Neuronal Aggregate Generating Seizures in the Rat Tetanus Toxin Model of Epilepsy

2002 ◽  
Vol 88 (6) ◽  
pp. 2919-2927 ◽  
Author(s):  
G. T. Finnerty ◽  
J.G.R. Jefferys

A key question in epilepsy is the organization and size of the neuronal networks necessary for generating seizures. Hypotheses include: a single focal neuronal network drives seizure discharges across the brain, which may or may not be identical with the circuits that generate interictal spikes; or multiple neuronal networks link together in re-entrant loops or other long-range networks. It remains unclear whether any of these hypotheses apply to spontaneous seizures in freely moving animals. We used the tetanus toxin chronic model of epilepsy to test the different predictions made by each hypothesis about the propagation and interaction of epileptic discharges during seizures. Seizures could start in either the injected or noninjected dorsal hippocampus, suggesting that seizures have multifocal onsets in the tetanus toxin model. During seizures, individual bursts propagated in either direction, both between the right and left dorsal hippocampi, and between CA3 and the dentate gyrus in the same hippocampus. These findings argue against one site “driving” seizures or seizures propagating around a limbic loop. Specifically, the side leading each burst switched a median of three times during the first 20 s of a seizure. Analysis of bursts during seizures suggested that the network at each recording site acted like a neuronal oscillator. Coupling of population spikes in right and left CA3 increased during the early part of seizures, but the cross-correlation of their whole-discharge waveforms changed little over the same period. Furthermore, the polarity of the phase difference between population spikes did not follow the phase difference for complete discharges. We concluded that the neuronal aggregate necessary for seizures in our animals comprises multiple spatially distributed neuronal networks and that the increased synchrony of the output (population spike firing) of these networks during the early part of seizures may contribute to seizure generation.

2013 ◽  
Vol 2013 ◽  
pp. 1-9 ◽  
Author(s):  
Dirk-Matthias Altenmüller ◽  
Jonas M. Hebel ◽  
Michael P. Rassner ◽  
Silvanie Volz ◽  
Thomas M. Freiman ◽  
...  

Purpose. In neocortical epilepsies not satisfactorily responsive to systemic antiepileptic drug therapy, local application of antiepileptic agents onto the epileptic focus may enhance treatment efficacy and tolerability. We describe the effects of focally applied valproate (VPA) in a newly emerging rat model of neocortical epilepsy induced by tetanus toxin (TeT) plus cobalt chloride (CoCl2).Methods. In rats, VPA (n=5) or sodium chloride (NaCl) (n=5) containing polycaprolactone (PCL) implants were applied onto the right motor cortex treated before with a triple injection of 75 ng TeT plus 15 mg CoCl2. Video-EEG monitoring was performed with intracortical depth electrodes.Results. All rats randomized to the NaCl group died within one week after surgery. In contrast, the rats treated with local VPA survived significantly longer (P<0.01). In both groups, witnessed deaths occurred in the context of seizures. At least3/4of the rats surviving the first postoperative day developed neocortical epilepsy with recurrent spontaneous seizures.Conclusions. The novel TeT/CoCl2approach targets at a new model of neocortical epilepsy in rats and allows the investigation of local epilepsy therapy strategies. In this vehicle-controlled study, local application of VPA significantly enhanced survival in rats, possibly by focal antiepileptic or antiepileptogenic mechanisms.


2001 ◽  
Vol 86 (6) ◽  
pp. 2748-2753 ◽  
Author(s):  
G. T. Finnerty ◽  
M. A. Whittington ◽  
J.G.R. Jefferys

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 naı̈ve 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 naı̈ve hippocampal slices by blocking GABAB 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.


1940 ◽  
Vol 60 (3) ◽  
pp. 322-333 ◽  
Author(s):  
M. Macgregor ◽  
James Ritchie

In the early part of 1937, during the course of excavations for a sewage extension tunnel at Queen's Park, on the south side of Glasgow, some pieces of bone were obtained by the workmen from a bed of gravel at a depth of 70 feet from the surface. Through the kindness of Mr T. Somers, Master of Works and City Engineer to the Corporation of Glasgow, these remains were loaned to the Geological Survey and, again with his sanction, submitted for examination to Professor James Ritchie of Edinburgh University, one of the collaborators in this note. Professor Ritchie reported that the fragments of bone fitted together to form the greater part of the right radius and ulna of a reindeer. At a later stage of the excavations a portion of an antler was disinterred from the same bed. It seems desirable to record these occurrences in some detail, and for convenience this communication has been divided into two parts. In the first of these the geological position and age of the fossiliferous deposit are briefly discussed, while the second part is devoted to a description of the remains themselves and to a comparison with similar remains elsewhere.


2017 ◽  
Vol 1 (S1) ◽  
pp. 56-56
Author(s):  
Shaun Evan Gruenbaum ◽  
Roni Dhaher ◽  
Amedeo Rapuano ◽  
Tore Eid

OBJECTIVES/SPECIFIC AIMS: We previously developed a translationally relevant model of temporal lobe epilepsy (TLE) in which glutamine synthetase is irreversibility inhibited by methionine sulfoximine (MSO), resulting in spontaneous seizures and dentate hilar neuron loss. The objective of this study was to determine the effects of chronic BCAA ingestion on neuronal viability in the dentate hilus in the MSO model of TLE. METHODS/STUDY POPULATION: Sixteen rats were randomly divided into 2 groups: 8 rats drank a 4% aqueous solution of all 3 BCAAs (BCAA group) ad libitum for 31 days, and the other 8 rats drank regular water (control group) for the same period. After 10 days of drinking, a microinfusion cannula (Alzet osmotic pump, model 2004) was surgically implanted in the right dentate gyrus to continuously infuse MSO at a rate of 0.625 g/hour for 28 days. After 31 days of drinking, rats were perfused transcardially with 0.9% NaCl followed by 4% paraformaldehyde in phosphate buffer. The brains were removed and fixed, sectioned on a Vibratome at 50-μm thickness, and were mounted on a gelatin-coated slides and stained with NeuN. Neuron counts in the hilar region were performed ipsilateral and contralateral to the infusion site using a stereological technique. RESULTS/ANTICIPATED RESULTS: Rats in the BCAA group had 37% fewer neurons in the ipsilateral dentate hilus than the control group (5.8×10−4±6.8×10−5 vs. 8.9×10−4±5.6×10−5 cells, respectively, p<0.01). Similarly, rats in the BCAA group had 39% fewer neurons in the contralateral dentate hilus than the control group (5.0×10−4±5.8×10−5 vs. 7.0×10−4±3.4×10−5 cells, respectively, p=0.01). DISCUSSION/SIGNIFICANCE OF IMPACT: This study demonstrates that chronic ingestion of BCAAs aggravates hilar neuronal loss in a translationally relevant rodent model of MTLE. This study gives important insight into how BCAAs may affect neuronal viability. Although the role of BCAAs on seizure activity is poorly understood, these results suggest that BCAAs may play an important role in neurochemical modulation and neurotoxicity.


Mr. Knight begins his paper by stating, that every tree, in the usual course of its growth, generates the buds that expand in the succeeding spring; but if these buds are destroyed, during the winter or early part of the spring, other buds are in many species generated; which buds perform the office of those that previously existed, except that they never afford blossoms or fruit. This reproduction of buds has not escaped the notice of naturalists; but it does not appear that they have ascertained from which of the various substances of the tree the reproduced buds derived their origin. After noticing some erroneous opinions respecting the origin of buds, Mr. Knight proceeds to relate some observations and experiments made by him on this subject. If the fruit-stalks of the Sea Cale ( Crambe maritima ) are cut off in the spring, the medullary substance decays, and a cup is formed, the sides of which consist of a woody substance, perfectly similar to the alburnum of trees. From the interior part of this substance, new buds are frequently generated in the ensuing spring: hence it is obvious, that the buds, in this case, do not spring from the bark; but it is not equally evident that they do not spring from some remains of the medulla.


1967 ◽  
Vol 39 (2) ◽  
pp. 78-89
Author(s):  
Paavo Elonen ◽  
Lasse Nieminen ◽  
Osmo Kara

In the dry summers 1964, 1965 and 1966, irrigation experiments of spring cereals were carried out on clay soils in Southern Finland. The soils having a rather poor structure because of the long-term cultivation without leys, endured without slaking the irrigation which was applied with »slow sprinklers» in the nigh-time. Neutral irrigation water containing small amounts of soluble salts was taken from a brook and a lake. One irrigation of 30—37 mm, applied at the optimum date, increased the grain yields of spring wheat 600—1000 kg/ha or 25—50 % and those of barley and oats 1600 kg/ha or 50 %. Barley and oats were the experimental plants only in 1966, when the relative increase in yields of all the three cereals were of the same order, namely 50 %. The optimum date of irrigation did not very closely depend on the state of development of the cereals, since within 2—5 weeks from sprouting about equal increases in yield could be obtained. Barley and oats responded, however, best to the irrigation applied one week before ear emergence. The late irrigation which was applied three days after ear emergence was best utilized by oats. Thus, the right order to irrigate cereals was in 1966: wheat, barley and oats, in spite of the reverse order of the ripening of the crops. An irrigation at the stage of sprouting had no effect on yield, because the sprouting occured well also without irrigation. Irrigation produced higher increases in yield when higher amounts of fertilizer were used. Thus, the profitable influence of irrigation was at least partly based on the better recovery of fertilizer nutrients by plants. Placement of fertilizer into the depth of 8—12 cm postponed the optimum date of irrigation some days, because the crops were able to make use of placed fertilizer also without irrigation in the early part of the summer. Placement of fertilizer and irrigation together formed an advantageous combination, because the influence of the placement of fertilizer was most effective immediately after sprouting whereas the best period of irrigation began 2—3 weeks later. With these both means, in the best cases, the yields could be almost doubled.


1998 ◽  
Vol 201 (11) ◽  
pp. 1719-1728
Author(s):  
H Schuppe ◽  
M Burrows

Locusts are usually quiescent at night, but this state can be interrupted by spontaneous periods of motor activity, or arousals, that can also be induced by exposure to light stimuli. To investigate whether repeated arousing stimulation has any lasting effect on behaviour, locusts were confronted at night with a series of 1 s light stimuli. Groups of three stimuli at intervals of 60 s were repeated 11 times at 10 min intervals during the first experimental night, and three stimuli at intervals of 90 s were repeated at 15 min intervals during the next night. Arousals and the effects of stimulation were monitored as changes in the spike activity of muscles in the basal part (the scapus) of the right antenna. In the early part of the night preceding the presentation of the light stimuli, neither 60 s nor 90 s periods were present as significant peaks in spontaneous changes in spike activity. The initial stimulus of a series evoked an arousal response that habituated on repetition of the stimulus. The end of the series of stimuli was followed by changes in spike activity that tended to have the same periodicity as the preceding stimuli. Furthermore, a single light stimulus at the end of the night evoked changes in spike activity that again tended to have the same periodicity as the preceding entraining stimuli. Repeated stimulation may therefore establish a memory trace for the period of stimulation that can be recalled either spontaneously or by the application of an appropriate external stimulus.


2017 ◽  
Vol 118 (5) ◽  
pp. 2865-2883 ◽  
Author(s):  
Toshi Nakajima ◽  
Haruka Arisawa ◽  
Ryosuke Hosaka ◽  
Hajime Mushiake

To investigate the role of interhemispheric β-synchronization in the selection of motor effectors, we trained two monkeys to memorize and perform multiple two-movement sequences that included unimanual repetition and bimanual switching. We recorded local field potentials simultaneously in the bilateral supplementary motor area (SMA) and pre-SMA to examine how the β-power in both hemispheres and the interhemispheric relationship of β-oscillations depend on the prepared sequence of arm use. We found a significant ipsilateral enhancement of β-power for bimanual switching trials in the left hemisphere and an enhancement of β-power in the right SMA while preparing for unimanual repetition. Furthermore, interhemispheric synchrony in the SMA was significantly more enhanced while preparing unimanual repetition than while preparing bimanual switching. This enhancement of synchrony was detected in terms of β-phase but not in terms of modulation of β-power. Furthermore, the assessment of the interhemispheric phase difference revealed that the β-oscillation in the hemisphere contralateral to the instructed arm use significantly advanced its phase relative to that in the ipsilateral hemisphere. There was no arm use-dependent shift in phase difference in the pairwise recordings within each hemisphere. Both neurons with and without arm use-selective activity were phase-locked to the β-oscillation. These results imply that the degree of interhemispheric phase synchronization as well as phase differences and oscillatory power in the β-band may contribute to the selection of arm use depending on the behavioral conditions of sequential arm use. NEW & NOTEWORTHY We addressed interhemispheric relationships of β-oscillations during bimanual coordination. While monkeys prepared to initiate movement of the instructed arm, β-oscillations in the contralateral hemisphere showed a phase advance relative to the other hemisphere. Furthermore, the sequence of arm use influenced β-power and the degree of interhemispheric phase synchronization. Thus the dynamics of interhemispheric phases and power in β-oscillations may contribute to the specification of motor effectors in a given behavioral context.


2003 ◽  
Vol 72 (2) ◽  
pp. 251-275 ◽  
Author(s):  
Michael C. Paul

Episcopal election in Western Christianity evolved considerably over the course of the fifth to the twelfth centuries. In the early part of this period, an open electorate consisting of the clergy and the people (clerus et populus), as well as the diocesan clergy and the metropolitan archbishop, all took part in the election and consecration of a new bishop. Over the course of several centuries, the local prince came increasingly to dominate the process due both to Germanic and Roman traditions of the role of the prince and to the growth in power of the local rulers over the course of the Middle Ages. Efforts to harmonize the discordant views of a “democratic” versus an elite (either princely or clerical) electorate with the ideals of canon law, which forbade lay participation in episcopal election, led to assertions that the clergy were to elect the bishop with the people and the prince giving their assent to the bishop-elect. However, with the Gregorian reforms of the twelfth century, the right of the clergy in episcopal elections became preeminent as the reformers sought to enforce the canon laws and exclude the laity from episcopal election, especially in light of past princely abuse. Despite the apparent victory of the reformers in the Investiture Controversy, the local ruler continued to play a preeminent role in episcopal appointments (or elections) into modern times, though the principle of election “by the clergy and the people” fell into disuse.


2013 ◽  
Vol 54 ◽  
pp. 492-498 ◽  
Author(s):  
Premysl Jiruska ◽  
Anan B.Y. Shtaya ◽  
David M.S. Bodansky ◽  
Wei-Chih Chang ◽  
William P. Gray ◽  
...  

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