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Biomedical subjects

J A Wada

Publications and source records attributed to J A Wada.

At least 37 records · Page 2Linked to original sources

Kindling of the massa intermedia of the thalamus in rats.

The kindling response of the massa intermedia (MI) was assessed in rats. Clinical manifestation of the MI kindling was generally similar to that of limbic kindling, and positive transfer to the amygdala (AM) was obtained following MI kindling. However, MI kindling showed (1) a relatively high after discharge threshold which sometimes increased during the course of kindling, (2) a seizure stage instability with frequent regression to earlier stages, (3) a failure to establish a generalized seizure triggering threshold with an 'all-or-none' property, and (4) a generalized tonic-clonic seizure, which was quite different from a kindled limbic seizure, during early phase of kindling. Furthermore, the MI stimulation caused violent beating movement of the forelimbs, jumping, or running regardless of presence/absence of afterdischarge. The findings suggest that mechanisms other than a simple activation of limbic structures are involved in the process of MI kindling.

Animals↗

Increased activity of superoxide dismutase in kindled brain and suppression of kindled seizure following intra-amygdaloid injection of superoxide dismutase in rats.

The possible role played by superoxide dismutase (SOD), a major defense system for counteracting the toxic effects of oxygen free radicals, in amygdaloid (AM) kindling was examined in rats. A significant increase of total SOD activity in the whole brain was observed 30 days after completion of AM kindling. Intra-AM injection of 3 ng of one of the 2 SOD enzymes present in mammalian brain, i.e. cytosolic SOD containing copper and zinc (CuZn-SOD) caused suppression of kindled seizure. These results suggest that SOD participates in the persistence of AM kindled seizure susceptibility and the initiation of kindled AM seizure.

Amygdala↗

Transhemispheric horizontal channels for transmission of epileptic information.

1) To gain insight into the complex pathophysiology of epilepsy in the human brain, the synthesis of information derived from various animal models representing appropriate components of human epileptic seizure is required. For epileptic seizure propagation, the availability of anatomical pathways and their physiological connectivity according to the site of seizure origin must be considered. The reason for the notion of a preferential nature of certain pathways over others remains unknown but may be due, in part, to past history and the participation of a genetically-determined differential susceptibility. In this context, the following factors need to be considered: a) the significance of use-dependent functional/structural change of the neuronal system, b) the importance of understanding the divergent nature of neuronal connectivity, the potential role of genetic predisposition, and c) the morphological difference which exists according to ascending phylogenesis and hence the presumable functional difference across the species. 2) The corpus callosum is the major and rapid route of transhemispheric transmission of epileptic seizure in man. In the case of seizure of temporal lobe origin, its transhemispheric transmission may use the temporalipsilateral frontal through the corpus callosum to the contralateral frontal and then to the contralateral temporal limbic system. In contrast, the significance of the anterior commissure and the hippocampal commissure in man is debatable since both of these pathways have a very definite regressive tendency according to ascending phylogenesis. The specific reason why these pathways are sometimes used in a minority of temporal lobe seizure cases remains unknown.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Failure of nine-month phenobarbital administration to reverse amygdaloid-kindled seizure susceptibility in cats.

Upon completion of left amygdaloid kindling, 4 cats underwent long-term phenobarbital administration during the subsequent 5- to 9-month rest period. Plasma phenobarbital levels were maintained above 15 to 20 micrograms/ml and were restimulated following plasma phenobarbital washout. Three cats served as nonmedicated controls. All 7 cats were subjected to repeated 6-hour sleep monitoring for observation of interictal discharges, which were observed most often in the immediate postictal period. Their frequency decreased gradually throughout the experiment in both the medicated and control animals, but they never completely disappeared except from the contralateral amygdala in 1 medicated animal. Upon primary site restimulation, all of the medicated animals responded with a generalized convulsion once the afterdischarge was induced. When these animals underwent secondary-site amygdaloid kindling, 3 showed a positive transfer effect. The findings suggest that although phenobarbital is a potent anticonvulsant, it has little effect on the acquired seizure susceptibility of previously amygdaloid kindled cats.

Amygdala↗

PET, CT, and MRI imaging of neuronal migration anomalies in epileptic patients.

During the investigation of intractable epilepsy, neuronal migration anomalies [NMA] were discovered in three patients. The first patient had abnormally positioned gray matter within the walls of both lateral ventricles. The second patient had a post operative cystic area in the right parietal-occipital lobes and an area of NMA within the right temporal lobe. The third patient had abnormally thickened gray matter in the right operculum. Long term CCTV-EEG monitoring of these three patients revealed ictal discharges originating from the area of abnormal gray matter in patients 2 and 3. PET scanning showed the areas of NMA in all three patients to have similar metabolic activity to normal gray matter. These cases illustrate the value of various imaging modalities and suggest some interesting physiology of a spectrum of neuronal migration anomalies.

Adolescent↗

Bidirectional transfer between kindling induced either by L-glutamate or L-aspartate and electrical stimulation in rats.

Repeated spaced injections into the amygdala (AM) of rats of a subconvulsive dose of either L-glutamate (GLU) or L-aspartate (ASP) produced progressive seizure development culminating in generalized convulsion strikingly similar to electrically kindled seizure. Both GLU- and ASP-kindled AM sites responded to electrical stimulation with very rapid development of kindled seizure. When electrically kindled AM sites received identical injections of GLU or ASP, a similar positive transfer effect was obtained. These results suggest that (1) either GLU or ASP alone can kindle the AM and (2) GLU, ASP or GLU/ASP kindling share common neurobiological mechanisms with electrical kindling.

Amygdala↗

Suppression of amygdaloid kindled convulsion following unilateral injection of 2-amino-7-phosphonoheptanoic acid (2-APH) into the substantia innominata of rats.

The comparative effect of intracerebral injection of 2-APH, a selective antagonist for N-methyl-D-aspartate (NMDA) receptors, into the substantia innominata (SI) and the amygdala (AM) of AM-kindled rats was examined. The intra-SI injection (ipsilateral to the kindled AM) induced a transient incoordination followed by immobility with loss of the rightening reflex, beginning at about 5 min following the injection and lasting for about 3 h. When the animals were stimulated at the previously established generalized seizure triggering threshold (GST) 45 min after the injection, the kindled seizure regressed to earlier stages although the afterdischarge (AD) duration remained unchanged. At 24 h, kindled seizure was readily activated at the GST. When 2-APH was injected into the kindled AM, no behavioural change occurred but AM stimulation at the GST failed to produce AD 45 min after the injection. Kindled seizure could be elicited, however, when the stimulus intensity was increased. This elevation of the GST lasted for 1-18 days. The findings suggest that NMDA receptors in the AM and SI play a differential role in AM seizure initiation and propagation, respectively. They also provide further support to the role presumed to be played by the SI in transforming the limbic seizure into motor seizure.

2-Amino-5-phosphonovalerate↗

Feline amygdaloid kindling and sleep.

Six hourly polygraphic examinations of sleep organization were made before and after amygdaloid (AM) kindling in 7 cats. After completion of AM kindling and the repetitive induction of kindled convulsion, the percentage of time spent in rapid eye movement sleep (REMS) significantly decreased, although the animals began to spend significantly more time in sleep. This altered sleep pattern persisted during an extended 22.5 h recording in 2 cats. The decreased waking (W) and REMS, as well as the increased slow wave sleep (SWS), appeared to be due to changes in mean duration but not in the total number of periods. Suppression of REMS but not SWS was also manifested as a delayed onset of REMS following sleep onset, the latency of which remained constant upon placement of animals in the recording chamber. These changes in sleep organization were transient, however, as they returned completely to the baseline pre-kindling level after a rest interval of 3-4 weeks without kindling stimulation. It is concluded that sleep organization changes, particularly those characterized by the suppression of REMS, are independent of the acquisition of AM-kindled seizure susceptibility; rather they are the direct correlates of generalized convulsion itself.

Amygdala↗

Practical digital filters for reducing EMG artefact in EEG seizure recordings.

In long-term scalp EEG monitoring of epileptic patients it is virtually impossible, in the present state of the technology, to avoid movement-related artefacts. These often obscure EEG information about the location of the seizure focus. One important example of such artefact is EMG activity. Its removal or suppression is sometimes enough to make otherwise useless EEG traces readable. Different methods of filtering have been applied towards that end. We routinely use a 15 Hz setting on our polygraph in obtaining EEG seizure printouts. We have recently examined digital filters which attenuate EMG beyond what is possible with the 15 Hz filter. A concern has been that the filters are practical in that they run in real time on a simple microprocessor and cause a minimum of confusion between smoothed artefact and actual brain activity.

Electroencephalography↗

Emotional facial expressions at the onset of temporal lobe seizures: observations on scalp and intracranial EEG recordings.

The initial facial expressions of 195 complex partial seizures of 98 patients with temporal lobe epilepsy were reviewed in relation to the laterality and focality of electroencephalographic (EEG) seizure origin. A neutral expression was observed most often (71) followed in frequency by expressions of disgust (13), happiness (7) and sadness (7). There was no expression of anger, surprise and fear. No correlation was found between the type of facial expression and the side of seizure origin. However, among 27 patients examined by means of intracranial EEG recordings, it was evident that a disgust expression occurred with oro-alimentary automatisms at the beginning of mesial temporal lobe seizures, whereas a happy one occurred without oro-alimentary automatisms at the beginning of lateral temporal lobe seizures. Although the facial expressions were not always related to the concurrent ictal emotion, it appeared that the majority of the patients with the disgust expression had autonomic features, while those of the happy/sad expression had psychic/sensory ones. It was concluded that (1) a disgust expression occurs as an indirect consequence of "crude sensation," while a happy/sad expression occurs as a direct consequence of "elaborate mental state" (Jackson) and (2) facial expressions must be reviewed in relation to focality rather than laterality in temporal lobe seizures.

Adolescent↗

Supplementary motor area kindling in the photosensitive baboons.

Two Senegalese baboons (Papio papio) were subjected to daily electrical stimulation at the SMA. When compared with the results of kindling at different frontal cortical sites, ADT and GST at the SMA were lower than those at other sites. On the other hand, the number of stimulations required for Stage 4 asymmetrical generalization was much greater at the SMA (mean of 78.0) than that for the PMA (22.5). These findings suggest that partial seizure originating from the PMA rather than the SMA seems to have a better access to the mechanisms underlying secondarily generalized convulsive seizure despite exquisite susceptibility to AD generation at the latter.

Animals↗

Premotor cortical kindling interferes with subsequent hippocampal kindling.

Interaction between the neocortical motor system and the limbic system was investigated in terms of the transfer of kindling. Premotor cortical kindling induced limbic seizures accompanied by dissociated hippocampal afterdischarges (AD) which outlasted the premotor AD. Subsequent kindling of the hippocampus was markedly retarded despite prolonged hippocampal AD. These results suggest that premotor cortical kindling induces a neuronal mechanism which prevents limbic access to the motor system.

Animals↗