慢性癫痫大鼠海马内GABA_A受体γ_2亚单位的改变──原位杂交组织化学研究

将马桑内酯作腹腔注射诱发大鼠慢性癫痫动物模型。然后，对模型动物和对照动物海马组织进行ＧＡＢＡ_Ａ受体γ_２亚单位的原位杂交组织化学研究。结果表明，慢性癫痫动物海马回和齿状回内的ＧＡＢＡＡ受体γ_２亚单位ｍＲＮＡ较对照组明显减少。提示ＧＡＢＡＡ受体γ_２亚单位可能在癫痫发病机理中起一定作用。     

Convulsions and wet-dog shakes produced by systemic or intrahippocampal administration of ruthenium red in the rat

Summary In this work we have studied in the rat the behavioral effects of the intraperitoneal (i.p.) and intrahippocampal (i.h.) administration of ruthenium red (RuR), an inorganic dye which has been shown to inhibit neurotransmitter release in synaptosomes. The i.p. injection induced initially flaccid paralysis and subsequently generalized tonic-clonic convulsions. It contrast, unilateral RuR microinjection into the CA₁ area of the hippocampus produced complex seizure behavior and wet-dog shakes (WDS). The i.p. administration of the serotonin receptor antagonist ketanserin markedly inhibited the WDS induced by i.h. RuR. In contrast, the i.h. injection of ketanserin and of the -aminobutyric acid (GABA) agonists 4,5,6,7-tetrahydroisoxazol[5,4-c]pyridin-3-ol (THIP) and baclofen together with RuR did not affect the frequency of WDS nor the seizure behavior. However, the i.h. injection of the GABA uptake blocker nipecotic acid, simultaneously with RuR, increased the frequency of WDS. The release of [³H]GABA, measured in synaptosomes of different cerebral structures of the rats injected i.p. with RuR, and in slices of the CA₁ area after i.h. injection of the dye, was not affected. Histological observations of the injected area showed a specific and intense staining of the somas of the CA₁ pyramidal neurons. It is concluded that the convulsant action induced by i.h. RuR microinjection is probably the result of an increased excitability of these CA₁ neurons, which is independent of any action on GABA release.     

Expanding the phenotypic spectrum of Mabry Syndrome with novel PIGO gene variants associated with hyperphosphatasia,intractable epilepsy,and complex gastrointestinal and urogenital malformations

Mabry syndrome is a glycophosphatidylinositol (GPI) deficiency characterized by intellectual disability, distinctive facial features, intractable seizures, and hyperphosphatasia. We expand the phenotypic spectrum of inherited GPI deficiencies with novel bi-allelic phosphatidylinositol glycan anchor biosynthesis class O (PIGO) variants in a neonate who presented with intractable epilepsy and complex gastrointestinal and urogenital malformations.     

Synaptic and non-synaptic mechanisms underlying low calcium bursts in the in vitro hippocampal slice

Summary 1. The epileptiform activity generated by lowering extracellular [Ca⁺⁺] was studied in the CA1 subfield of rat hippocampal slices maintained in vitro at 32° C. Extracellular and intracellular recordings were performed with NaCl and KCl filled microelectrodes. 2. Synaptic potentials evoked by stimulation of the stratum radiatum and alveus were blocked upon perfusion with artificial cerebrospinal fluid (ACSF) containing 0.2 mM Ca⁺⁺, 4 mM Mg⁺⁺. Blockade of synaptic potentials was accompanied by the appearance of synchronous field bursts which either occurred spontaneously or could be induced by stimulation of the alveus. 3. Both spontaneous and stimulus-induced low Ca⁺⁺ bursts recorded extracellularly in stratum pyramidale consisted of a negative potential shift with superimposed population spikes. This extracellular event was closely associated with intracellularly recorded action potentials rising from a prolonged depolarization shift. Steady hyperpolarization of the cell membrane potential decreased the amplitude of the depolarizing shift suggesting that synaptic conductance were not involved in the genesis of the low Ca⁺⁺ burst. 4. Spontaneous depolarizing inhibitory potentials recorded in normal ACSF with KCl filled microelectrodes were reduced in size in low Ca⁺⁺ ACSF. However, small amplitude potentials could still be observed at a time when low Ca⁺⁺ bursts were generated by hippocampal CA1 pyramidal neurons. 5. Bicuculline methiodide, an antagonist of -aminobutyric acid (GABA), was capable of modifying the frequency of occurrence and the shape of synchronous field bursts. The effects evoked by bicuculline methiodide were, however, not observed when 81–100% of NaCl was replaced with Na-Methylsulphate. Hence, it was concluded that in low Ca⁺⁺ ACSF even though large release of transmitter such as those following electrical activation of stratum radiatum or alveus cannot be observed, small spontaneous release of the inhibitory transmitter GABA seems to persist. 6. Substitution of NaCl with Na-Methylsulphate also caused changes in the synchronous field bursts which were different from those observed following application of bicuculline methiodide. These findings suggest that in low Ca⁺⁺ ACSF, in addition to residual GABAergic Cl^- mechanisms, non-synaptic Cl^- conductances might play a role in controlling the excitability of hippocampal neurons.Supported by grants from the MRC of Canada (MA-8109) and Sick Children Foundation to MA     

Hemispheric Prevalence Changes in Partial Epileptic Patients on Perceptual and Attentional Tasks

In relation to the general issue of the long-term effects of epileptic activity on the higher nervous functions, monohemispheric epileptic patients--divided into "lesional" [i.e., with computed tomography (CT) scan-visible lesions] and "nonlesional" (i.e., with CT scan-nonvisible lesions)--were submitted to dichotic verbal and tonal tasks, dichoptic verbal and spatial tasks, and a visual tachistoscopic attentional task. The aim was to investigate whether the typical patterns of hemispheric prevalence, which were observed in normal subjects by using these tests, undergo significant changes in epileptic patients. The findings versus normal subjects seem to demonstrate that (a) in lesional epileptic patients, the prevalence of the hemisphere without macroscopic lesions is a constant rule, whether or not this hemisphere is prevalent in normal subjects; (b) in nonlesional epileptic patients, the patterns are the following: when the epileptic hemisphere is the one that is prevalent in normal subjects, its prevalence is enhanced, whichever the hemisphere; when the epileptic hemisphere is not the hemisphere prevalent in normal subjects, the left one attracts and maintains prevalence, whereas the right one reduces and variously interferes with contralateral prevalence. It is concluded that, with respect to the functions tested, the nature of the epileptic foci seems to influence markedly the interhemispheric prevalence pattern.     

Alcoholism and Epilepsy

There is a scarcity of population-based epidemiological investigations concerning the prevalence of epilepsy among alcoholics, and of alcoholism among epileptic patients. Available data seem to suggest that the prevalence of epilepsy among alcoholics is at least triple that in the general population, and that alcoholism may be more prevalent among epileptic patients than in the general population. The term "alcoholic epilepsy" has been used with varying definitions in different investigations. It is suggested that a uniform definition be adopted so as to minimize confusion when comparing data from different laboratories. Although there is general agreement that excessive alcohol intake can increase the frequency of seizures in epileptic patients, limited available data suggest that light to moderate social alcohol drinking may not affect seizure frequency. However, epileptic patients should be warned about the possible adverse effects of alcohol, especially those who have refractory forms of epilepsy. Except for a few anomalous cases, evidence for the direct seizure-provoking effect of alcohol is not strong. This is because it is difficult to pinpoint alcohol as the only etiology; more likely, alcohol is only one factor among others (e.g., head trauma, cerebral infarct, alcohol withdrawal, and metabolic effects of alcohol) in provoking seizures. Because seizures are a symptom and not a disease, it is often difficult to distinguish epileptic seizures from alcohol-withdrawal seizures. Patients with only the latter kind of seizures should not need chronic antiepileptic medication.     

Psychogenic relapses in childhood epilepsy in puberty and adolescence

Summary Epileptic patients who, after years of being free from symptoms, have relapses during puberty or adolescence (some-times coinciding with a reduction in therapy) pose special therapeutic and diagnostic problems. Because of pubertal lability, the cause of a relapse might seem to be organic, especially if the EEG also shows a deterioration; yet psychogenic factors must not be disregarded. On the basis of typical case studies, a characteristic constellation is presented. The achievement of a well-behaved child at first daramatically improves and this correlates with the success of antiepileptic therapy. Then individuation and further development cannot adequately take place because the family unit is not functioning properly. At a critical stage of development, the excessive expectations of the parents lead to too much stress on the child, thus destroying the balance within the family system, which has hitherto been maintained only with difficulty. Attempts to improve the situation by changing the medication (increasing the dose or switching to another drug) fail. If, however, it is realized that the symptoms are of psychogenic origin, adequate therapeutic interventions (e.g. adequate schooling or professional training as well as psychotherapy) promise good results.     

Partial epilepsy in neurologically normal children: clinical syndromes and prognosis

A clinical and electroencephalographic study of 107 neurologically normal children with partial seizures was undertaken to verify the existence and determine the frequency of epileptic syndromes reported in selected populations. Sixty-three children had simple partial seizures, 39 had complex partial seizures, and 5 children were unclassifiable. The syndrome of benign partial epilepsy of children with rolandic spikes (BPEC, 38 cases) was clearly identified and its uniformly benign final prognosis was confirmed even if some of these children had at times severe or poorly controlled seizures. Among the children with simple partial seizures outside the BPEC (25 cases) and complex partial seizures (39 cases), no homogeneous clinical or electroclinical subgroup could be found. Two children with benign partial epilepsy and myoclonic-astatic seizures ("atypical benign partial epilepsy of childhood") and one child with "benign epilepsy with occipital spike-waves" were identified. 74% of children with epilepsy with complex partial seizures (ECP) had a 1-year seizure-free interval, and many children with epilepsy with simple partial seizures outside the BPEC group (ESP) had no more than two seizures. A benign course is thus not limited to the BPEC but is difficult to predict. Prospective studies are necessary to confirm the existence of well-defined benign syndromes among the idiopathic partial epilepsies of childhood, which appear quite rare outside the BPEC.     

Differences in Penicillin-Induced Synchronous Bursts in the CA1 and CA3 Regions of the Hippocampus

Epileptiform field potentials were compared in the CA3 and CA1 regions of penicillin-treated hippocampal slices. The CA3 field bursts usually began with decrementing spike patterns similar to reported single-unit bursts, whereas spike amplitude gradually increased in spontaneous and long-latency CA1 bursts. Stimuli close to CA1 recording sites also evoked short-latency, decrementing CA1 responses. We postulate that these patterns reflect a more rapid recruitment of CA3 neurons into synchronous bursts and a gradual sequential activation of the CA1 neurons by Schaffer collateral input from CA3. Stimulation of stratum radiatum close to CA1 also produced long-latency "all-or-none" bursts in CA3 and then CA1, identical to spontaneous bursts and those produced by stimulation remote from CA1. At threshold, 76% of the latency to the CA1 burst occurred between the stimulus and the onset of the CA3 burst. The latency to the CA3 burst decreased with increasing stimulus intensity but the intervals from CA3 to CA1 bursts remained constant. Thus, long-latency CA1 bursts appear to be due to antidromic activation of CA3 followed by reexcitation of CA1.     

ZK 91296, a partial agonist at benzodiazepine receptors

ZK 91296 (ethyl 5-benzyloxy-4-methoxymethyl--carboline-3-carboxylate) is a potent and selective ligand for benzodiazepine (BZ) receptors. Biochemical investigations indicate that ZK 91296 may be a partial agonist at BZ receptors. Such partial agonism may explain to some extent why ZK 91296 needs higher BZ receptor occupancy than diazepam for the same effect against chemical convulsants and for behavioural effects. The lack of sedatiye effects, and the very potent inhibition of reflex epilepsy, spontaneous epilepsy and DMCM-induced seizures suggest, furthermore, that ZK 91296 may possess pharmacological selectivity for a particular type of BZ receptor interaction, perhaps including topographic as well as receptor subtype differentiation.