Seizure-sensitive Strain Research Articles

Application of Bicuculline to the Gerbil Somatosensory Cortex Induces Repetitive Ear Movements Accompanied by Induction of c-Fos Immunoreactivity in the Thalamus.

We previously established a seizure-sensitive strain of Mongolian gerbil, MGS/Idr, in which seizure-inducing stimuli often elicit repetitive backward jerks of the ears at the beginning of seizures, and found that unilateral application of (−)-bicuculline methiodide (BMI) to an area of the somatosensory cortex in this strain induced similar, but long-lasting, repetitive movements of the contralateral ear. In the present study, we have extended this observation by using immunohistochemistry to look for areas of the brain in which c-Fos protein, an immediate early gene product, appeared unilaterally following BMI application. At 4 hr after BMI application, the cerebral cortex under the application site showed intense c-Fos immunostaining. In addition, c-Fos immunoreactivity appeared in restricted areas of the ipsilateral thalamus, including the ventroposterior nucleus, posterior nucleus, and reticular nucleus. Control saline-treated gerbils did not show unilateral staining in the corresponding thalamic areas. These areas may form a network with the somatosensory cortex that is involved in the recurrent phenomena, as proposed for other areas of the cerebral cortex.

Manipulation of the somatosensory cortex modulates stimulus-induced repetitive ear movements in a seizure-sensitive strain of gerbil.

Some Mongolian gerbils (Meriones unguiculatus) respond to stimulation by seizures, the pattern of which changes progressively during development. We previously established a seizure-sensitive strain, MGS/Idr, in which all animals exhibit such stimulus-induced seizures. We have now noted that all adults of this strain also show repetitive backward movements of the ears at the ears at the beginning of stimulus-induced seizures, although the incidence varies with the individual. We examined whether the cerebral cortex was involved in these movements and found that electrical stimulation of an area of the somatosensory cortex elicited strong backward movement of the ear on the contralateral side, and that unilateral application of bicuculline, a GABAA receptor antagonist, induced spontaneous repetitive backward movements of the same ear. In this area, sharp waves appeared in the electrocortigram during the repetitive ear movements induced by seizure-inducing stimuli. Unilateral ablation of this area abolished stimulus-induced repetitive movements of the contralateral ear, but had no effects on those of the ipsilateral ear. These results suggest that, in certain types of seizure-susceptible subjects, it may be possible to modify stimulus-induced repetitive movements by manipulating a certain area of the somatosensory cortex which is related to these movements and that this gerbil strain may be useful in research on this subject.

Two types of aggregate in the cerebral cortex of a seizure-sensitive strain of the Mongolian gerbil

A 70-kDa protein, P70, found mostly in the pyramidal cells of the cerebral cortex of cobalt-induced epileptogenic rats, has been implicated in epileptogenesis. The presence of a P70-like substance was searched for immunohistochemically in the cerebral cortex of MGS/Idr, a seizure-sensitive strain of the Mongolian gerbil ( Meriones unguiculatus) that we previously established. Immunoreactive aggregates were observed in the pyramidal neurons of the motor cortex and the primary somatosensory cortex. Analysis using confocal laser scanning microscopy revealed that the aggregates were often colocalized with a second type of aggregate with red autofluorescence at the marginal zone of the cell somata. Both aggregates appeared and increased before the appearance of generalized tonic-clonic convulsion. These may be involved in some change of physiological function of the cerebral cortex but their presence itself is not enough to determine the occurrence of epileptic seizure because the gerbils that showed no such seizure had both aggregates.

Facial Nerve Innervating Pinnae Muscles of the Gerbil: Three-Dimensional Construction with Respect to Neighboring Structures.

The Mongolian gerbil (Meriones unguiculatus) is an animal model of epilepsy in which the epileptic behaviors develop along with chronological development. In this study, to clarify the mechanism of epileptogenesis in the gerbil, the developmental change of the behaviors elicited by posture change was followed in the previously established animals of a seizure-sensitive strain and a-resistant one. Posture change is a strong inducer of seizure in the adult animals of the sensitive strain. The results show that a bilateral and synchronized rhythmical movement of the pinnae was induced in the young animals of the sensitive strain, which seemed to correspond to an earlier stage, if not the first, in the establishment of epileptogenesis. In contrast, posture change did not induce either the adult-type seizure or the characteristic movement of the pinnae in the animals of the resistant strain. As the first step in clarifying the reason for this difference between these two strains, we studied the structure of the facial nerve which innervates the muscle of the pinnae, using consecutive paraffin sections of decalcified heads of both strains.In both strains, the facial nerve left the brainstem, ran laterally along the vestibular nerve bundle and at the geniculate ganglion, it changed its direction posteriorly and laterally. When it left the skull, it changed its direction again and descended ventrally, extending a branch to the ear on its way. In the seizure-resistant gerbils, this branch entered the muscle in a similar way to the seizure-sensitive animals. Therefore, these two strains probably have difference (s) in other components although the possibility of a functional difference in the facial nerve remains.

Opioid mechanisms involved in the slow potential change and neuronal refractoriness during cortical spreading depression.

The slow potential change (spc) accompanying spreading depression (SD) was studied in rats and in a seizure-sensitive strain of Mongolian gerbil under three different experimental paradigms, each involving the use of naloxone. Gerbils undergoing electroconvulsive shock treatment displayed SD during the post-ictal phase, which was blocked by the intraperitoneal (i.p.) administration of naloxone (20-50 mg kg-1). Topical application of naloxone to the exposed cortex of the anaesthetized gerbil and rat blocked the spc of SD evoked by KCl. Microiontophoretic ejection of naloxone during extracellular recordings reversed cell refractoriness following the spc, demonstrated by the observation of a maintained sensitivity to iontophoretic pulses of glutamate. The results suggest a possible involvement of naloxone-sensitive processes in the mechanism responsible for cortical SD.

Hippocampal neuron loss in epilepsy and after experimental seizures.

In this study, the hippocampus and its relationship to epilepsy is reviewed from a neuropathological point of view. The variability found in previous studies regarding the extent of the damage to neurons makes interpretation difficult. The aim of this study was to clarify the neuron loss by quantitation. The neuron density in the different H-fields of the pyramidal band and in the granule cell area has been determined throughout the hippocampi by means of light microscope and an ocular grid. The brains of 20 patients with epilepsy were studied. The type of epilepsy was verified from the case history and encephalographic recordings. The distribution of neuron loss was evaluated by statistical analyses of variance applied to the different means and related to the clinical assessments. The normal neuronal distribution was evaluated in 29 persons without any known cerebral disorders. In experimental studies, the changes in neuron density in relation to seizures were determined. 8 rats were studied after electroconvulsive seizures, elicited 3 times daily for 50 days. 10 animals served as controls. 20 gerbils of a seizure-sensitive strain with different types of seizures, 5 in each group, were the object of the second experimental study which also included a group of 5 gerbils of the seizure-resistant type. The aim of this part of the study was to illustrate the damage to the neurons in relation to different seizure types. The main result of the study of patients with epilepsy was that neuron loss occurs in all areas investigated. The severely affected areas were field H3 and the granule cells. The neurons of field H1 seemed to be damaged earlier in life, possibly due to hypoxia accompanying generalized convulsions. The study of the normal neuronal distribution in the hippocampus revealed a neuronal reduction of 20% in old age. This ageing phenomenon was taken into account when evaluating the pattern of neuron loss in the patients with epilepsy. No specific pattern of neuron loss characterized the different types of epilepsy. Neuron loss was related to generalized convulsions and increased throughout life with the duration of the disorder. The experimental studies of rats revealed that no neuron loss occurred as a result of generalized convulsions alone. In contrast, the pyramidal neurons of fields H2 and H3 were reduced in the gerbils with frequent generalized convulsions. However, the number of seizures was low, in comparison with the number of generalized convulsions in rats. The hypothesis is put forward that the neuron loss in the gerbils in this area, known for its high bursting activity, is due to seizure-activity which has been shown by others to occur interictally. It was thus suggested that seizure-activity even without clinical seizures might be responsible for neuron loss in the hippocampus also in man, in relation to epilepsy of a certain intensity and duration. The consequences of this with regard to prevention of the development of severe epilepsy after single and even minor seizures and the choice of treatment in the individual cases are considered and future projects are mentioned.

Hippocampal neuron density and seizures in the Mongolian gerbil.

Mongolian gerbils of the seizure-sensitive strain exhibit epileptic seizures in relation to changes in the environment, a characteristic which has been increased to about 100% by inbreeding. The seizures vary from animal to animal but are rather stable in the individual animal, which makes it possible to study the neuron densities in the hippocampus of the gerbil in relation to seizure type and seizure intensity. Five groups of gerbils with seizures ranging from minor movements and motor arrest to intense generalized convulsions were investigated with a quantitative method including cell counting by light microscope and estimation of possible brain shrinkage, as well as determination of nucleoli and nuclei diameters. The cell densities were determined in different areas of the pyramidal cells of the hippocampus (H-fields). The study discloses a reduction of cell densities in fields H2 and H3 in relation to intense generalized convulsions. It is suggested that the reduction in cell density in field H2 is a result of seizure activity, whereas the field H3 cell loss can be the result of both the hypoxia and the seizure activity.