NMDA receptor activation during epileptiform responses in the dentate gyrus of epileptic patients.

We previously showed that a low frequency (1 Hz) train of perforant path stimulation evokes burst discharges in the dentate gyrus of hippocampal slices obtained from patients surgically treated for intractable temporal lobe epilepsy. We report here that multiple population spikes that characterize the burst discharge are blocked reversibly by the specific NMDA receptor antagonist, D-(-)-2-amino-5-phosphonovaleric acid (D-APV). The epileptiform discharge evoked in human dentate gyrus by stimulation trains of 1 Hz could be reproduced in the rat dentate gyrus in vitro by the same stimulation protocol but required the presence of low concentrations (0.2-0.6 mM) of extracellular magnesium. We suggest that low frequency orthodromic stimulation of dentate granule cells through the perforant path progressively evokes an increase in the activation of NMDA receptors resulting in burst discharges in tissue from epileptic patients.     

2-cyclohexene-1-one-induced hyperglycemia in the mice

2-Cyclohexene-1-one (CHX) dose-dependently caused the elevation of blood glucose levels in both fed and fasted mice. Adrenalectomy considerably prevented the elevated blood glucose with CHX, and plasma adrenaline assays revealed about a three- to fifteen-fold rise after CHX treatment. These findings indicate that the CHX-induced hyperglycemia may be largely mediated by adrenaline released from the adrenal medulla.     

Hyperexcitability associated with localizable lesions in epileptic patients

Intracellular recordings from neurons were carried out in cortical slices obtained from tissue removed from patients suffering from intractable seizures. The patients were divided into two groups based on the presence or absence of an anatomical abnormality that could be imaged preoperatively. The lesion or its surround was the presumptive epileptogenic area. The tissue removed from the patients without lesions was removed either for biopsy purposes or for access to epileptic tissue and was not considered epileptogenic. All neurons from patients without an imageable lesion, and some (19%) from patients with an imageable lesion, responded to orthodromic stimuli with a sequence of synaptic excitation followed by inhibition; these properties resembled those of normal rodent cortical slices. Different responses, classified as abnormal, were observed in 81% of the neurons in tissue specimens obtained near lesions. The most common was prolonged synaptic excitation with no noticeable inhibition, even at high stimulus strengths. In three resections, long latency all-or-none depolarization shifts were observed that resemble the classic paradoxical depolarization shift seen in in vivo extracellular recordings. Loss of specific inhibitory systems within the cortex may contribute in part to these abnormal responses.     

Episodic variations of prolactin, thyroid-stimulating hormone, luteinizing hormone, melatonin and cortisol in infertile women with subclinical hypothyroidism

Preliminary data have suggested that female infertility due to corpus luteum insufficiency may be caused by subclinical hypothyroidism [exaggerated thyroid-stimulating hormone (TSH) response to thyrotrophin- releasing hormone (TRH) stimulation]. L-Thyroxine supplementation has been recommended to achieve pregnancies in subclinical hypothyroid women. This controlled study was carried out in order to investigate the biochemical diagnosis of subclinical hypothyroidism as a possible infertility factor. Five infertile patients (aged 25-36 years) with subclinical hypothyroidism (n = 4, stimulated TSH >20 microU/ml) or primary hypothyroidism (n = 1) and five healthy controls (aged 22-39 years) with normal thyroid function (stimulated TSH <15 microU/ml), regular cycles and no history of infertility were studied in the early follicular phase. In the pre-study evaluation, eight of 23 volunteers (34.8%) had to be excluded because of subclinical hypothyroidism with stimulated TSH values (TSHs) >15 microU/ml. Cycle function of patients and controls was compared by the method of LH pulse pattern analysis. Therefore blood samples were drawn every 10 min during a 24 h period. Sleep was recorded from midnight to 7 a.m. Repetition of the TRH tests at the end of the 24 h blood sampling period confirmed the difference in stimulated TSH values of the two study groups. Pulse analysis for luteinizing hormone (LH), TSH and prolactin showed no differences between patients and controls for pulse frequency, amplitude, height, length, area under curve (AUC) and the 24 h mean. Even the hypothyroid patient had a normal LH pulse pattern. Additional measurement of melatonin in pooled sera every 30 min gave the well-documented diurnal profiles during day and night for both groups. Patients had significantly higher melatonin values at seven time points during the night. Peaks for LH, TSH, prolactin and cortisol were correlated with the sleep stages wake, rapid eye movement, 1 + 2 and 3 + 4. We concluded that corpus luteum insufficiency in female infertility cannot be explained by subclinical hypothyroidism and thus should not be treated with L-thyroxine for fertility reasons.