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Diabetes insipidus (DI) and other features of hypothalamic dysfunction were observed in two patients resuscitated following cardio-respiratory arrest (CRA). Both patients also developed marked hyperglycemia probably related to hypertonic dehydration. The development of DI in survivors of CRA suggests severe hypothalamic hypoxic injury and poor prognosis.

Injections of bombesin (BOM, 125, 250 and 500 ng) into the preoptic/anterior hypothalamus caused dose-related decreases of threshold temperatures for metabolic cold defence, cutaneous vasomotor tone and respiratory rate, combined with a reduced sensitivity of these thermoregulatory effectors in response to core temperature changes induced at thermoneutral or warm ambient conditions. Intracisternal (i.c.) injections of BOM (250 ng) produced qualitatively identical thermoregulatory effector changes in response to core temperature changes. Injections of BOM into the posterior hypothalamus did not affect body temperature control. Increased locomotor behavior, licking and grooming was elicited, however, from all injection sites. The results explain the prevailing hypothermic effect of BOM as the consequence of the concerted decrease in threshold temperatures and "gains" of all autonomic thermoregulatory effectors and suggest the activation of warm inputs, relative to cold inputs, at the hypothalamic level as the underlying mechanism. Direct or indirect inhibition of the intrinsic hypothalamic system involving thyrotropin-releasing hormone (TRH) and consequent deactivation of central noradrenergic pathways known to generate the entire autonomic pattern of cold defence might be involved in the neuro-humoral changes resulting in hypothermic effects of centrally applicated BOM.

Unilateral microinjection of neuropeptide Y (NPY) into the posterior hypothalamic nucleus was previously found to evoke an increase in mean arterial pressure (MAP) in urethan-anesthetized rats. In this study, the mechanism by which this increase occurs was examined. Pretreatment of rats with 2.0 mg/kg (iv) of phenoxybenzamine, or 7.5 mg/kg (iv) of pentolinium, resulted in a significant reduction in the peak MAP evoked by microinjection of NPY (2.35 nmol) into the posterior hypothalamic nucleus. Administration of the vasopressin V1-receptor antagonist [d(CH2)5Tyr(Me)]AVP (10 micrograms/kg iv) before microinjection of NPY failed to attenuate the increase in MAP. Similar results were obtained with respect to the effect of these three antagonists on the increase in MAP evoked by injection of the cholinergic muscarinic agonist carbachol (5.48 nmol) into the posterior hypothalamic nucleus. Furthermore, microinjection of NPY or carbachol elicited a significant elevation of renal sympathetic nerve activity and an increase in resistance of the hindquarter vascular bed. However, NPY elicited a decrease and carbachol an increase in the resistance of the mesenteric bed, whereas NPY elicited an increase and carbachol a decrease in the resistance of the renal bed. These results suggest that NPY elicits an increase in MAP via centrally mediated sympathetic excitation. Furthermore, NPY and carbachol differentially affect sympathetic outflow to peripheral vascular beds after microinjection into the posterior hypothalamic nucleus.

Clinico-encephalographic examinations of patients suffering from neuroses and neurosis-like states with marked vegetative disturbances were carried out. Regular connections between the integral electrographic phenomena and individual features of the EEG on the one hand, and the character and the depth of the vegetovascular, metabolic, endocrinal, emotional and neurotic disturbances on the other were revealed. The averaged models of EEGs constructed with the aid of an electronic computer can be used for ordinary practical evaluation of EEGs with the purpose of specifying the localization of the affection in individual links of the limboreticular system.

Barbiturates are often utilized clinically in circumstances in which elevated intracranial pressure is expected. In this study, the mechanism of action of barbiturates was examined in dogs with intracranial hypertension induced by injecting autogenous incubated blood into the chiasmatic cistern. Intracranial pressure and systemic blood pressure were continuously monitored. A single bilateral administration of powdered pentobarbital (2 mg and 0.4 mg) in experimental animals and solid d-glucose (2 mg) in control animals was given into the posterior hypothalamus, pontine reticular formation, or medullary reticular formation when intracranial pressure reached 20-30 mmHg after the blood injection--usually in 3-6 h. The increased intracranial pressure following the experimental subarachnoid hemorrhage was always associated with either intracranial pressure irregularities or concomitant blood pressure variations, suggesting the presence of vasomotor instability. Administration of both 2 mg and 0.4 mg of pentobarbital into the medulla caused a significant (P less than 0.01) decrease of the intracranial pressure to 44 and 65% of control and stabilization of the intracranial pressure irregularities, whereas pentobarbital given at the other sites did not. The blood pressure was also decreased significantly (P less than 0.01) to 80 and 88% of control and the blood pressure variations were stabilized in animals after administration of pentobarbital into the medulla, whereas in those given pentobarbital at the other sites, it was not. The results suggest that, in the presence of elevated intracranial pressure following experimental subarachnoid hemorrhage, the mechanisms of action of barbiturates in reducing the intracranial pressure may result from alleviation of cerebral vasomotor instability by depression of the vasomotor center of the medulla.

Polygraphic 23-hr recordings were carried out in 25 adult cats in order to examine the effects of both systemic and local injections of various histaminergic and antihistaminergic drugs on sleep-waking cycles. alpha-Fluoromethylhistidine (alpha-FMH), a specific inhibitor of histidine decarboxylase, when injected intraperitoneally at a dose of 20 mg/kg, induced a significant increase in deep slow wave sleep (S2) and a decrease in wakefulness (W), without modifying light slow wave sleep (S1) and paradoxical sleep (PS). Intraperitoneal injections of mepyramine (1 mg and 5 mg/kg), a well-known histamine H1-receptor antagonist, increased deep slow wave sleep and decreased wakefulness, as well as paradoxical sleep. Bilateral injections of alpha-FMH (50 micrograms/1 microliter) into the ventrolateral posterior hypothalamus, where histamine immunoreactive neurones have been recently identified, resulted in a significant decrease in wakefulness and increase in deep slow wave sleep. Similarly, injections of mepyramine (120 micrograms/1 microliter) in the same structures caused a significant decrease in wakefulness and an increase in deep slow wave and paradoxical sleep as well. In contrast, local injections of SKF-91488 (50 micrograms/1 microliter), a specific inhibitor of histamine-N-methyltransferase, led to a significant increase in wakefulness and decrease in both slow wave sleep (SWS) and paradoxical sleep. Injections of histamine, at doses of 5, 30 and 60 micrograms/1 microliter, also increased wakefulness and decreased slow wave sleep dose dependently, while these effects were completely blocked by pretreatment with mepyramine. The results suggest that histaminergic systems in the hypothalamus play an important role in arousal mechanisms and their actions are mediated through H1-receptors.

The author's studied the central action of seven beta-blocking agents: alprenolol, atenolol, bupranolol, oxprenolol, pindolol, practolol, propranolol. The drugs were stereotactically injected into the posterior hypothalamus of non anaesthesized rats. Three dosages were used. Blood pressure, heart rate and plasma renin activity (PRA) were recorded. 2. The seven beta-blocking drugs used decreased heart frequency for at least one dosages PRA always decreased but blood pressure was lowered only after administration of alprenolol, oxprenolol, pindolol. 3. The discussion deals with: --the specificity of the target, --the involvement of the central beta receptors into the PRA regulation, --the correlations between the cardiovascular responses and the pharmacological properties of the different molecules; the hypothetic role of the intrinsic activity is postulated --the dissociation between heart rate and blood pressure responses, suggesting the existence of two different receptors for the specific control of those two parameters.

The decorticate cat develops sequences of locomotor movements, especially in the two posterior limbs: those appear either spontaneously, or following a single shock applied to L7 dorsal root. Using this preparation, we tested the effects of two neuroleptic agents, Thioproperazine (TZ) and Sulpiride (S), through either systemic administration or local injection into the lateral-posterior hypothalamus and into the lumbar spinal cord. TZ administered i.v. (0.5 mg/kg) suppressed all locomotor rhythms, while S induced unclear effects. The tested drugs clearly acted at the hypothalamic level, but the effects of the drugs were opposite; TZ (70 microgram) suppressed rhythms, while S (350 microgram) increased or even induced them. T2 (50 microgram) injected at the L7 cord-level abolished rhythms, and S (350 microgram) reduced their amplitude but increased the duration of locomotor sequences. The flexion reflex was never affected by these drugs. The two drugs seem to act at the spinal and the hypothalamic levels. The possible mechanisms involved in their action are discussed.

The possible occurrence of central sympathetic dysfunction during development of spontaneous hypertension was studied by recording aortic pressure and sympathetic nerve activity concurrently during electrical stimulation of the posterior hypothalamus in 9-wk-old Kyoto-Wistar rats. Even at this early age, basal levels for both measurements were already elevated significantly in those with spontaneous hypertension. Increases in sympathetic neural firing induced by graded hypothalamic stimulation were always followed by corresponding increases in blood pressure; magnitude of both effects was appreciably larger in spontaneously hypertensive than in normotensive rats, as was the vasodepression caused by blocking autonomic ganglia with pentolinium. By contrast, pressor responses to injected norepinephrine were almost equal thereby suggesting that cardiovascular reactivity was unaltered and that enhanced responsiveness to hypothalamic stimulation was directly due to the concomitant increase in sympathetic nerve activity. Although the exact site from which sympathetic hyperactivity originates was unidentified, our results support the interpretation that sympathetic mechanisms involving the posterior hypothalamus participate in elevating blood pressure during development of spontaneous hypertension in rats.

Recent studies have shown that a GABAergic mechanism in the posterior hypothalamus modulates tonic levels of arterial pressure and heart rate and the bradycardiac response to baroreceptor stimulation. It has not been determined if this modulation involves an alteration of sympathetic discharge by an effect upon hypothalamic neurons. Therefore, the purpose of the present study was to determine if manipulation of GABAergic activity in the posterior hypothalamus altered sympathetic nerve discharge. Cervical nerve activity was recorded and processed as an indication of sympathetic activity in anesthetized, ventilated cats. Unilateral injections of a GABA antagonist (picrotoxin) into the posterior hypothalamus produced increases in both rhythmic and tonic sympathetic discharge, with concomitant increases in arterial pressure and heart rate. These responses were reversed by injections of a GABA agonist (muscimol) into the same site. Injections of the vehicle solution (Ringers) or muscimol without a prior injection of picrotoxin had no effect upon the sympathetic discharge. These results suggest that a GABAergic mechanism exerts a tonic inhibitory effect upon sympathetic discharge by an action in the posterior hypothalamus.

The tumour aetiology of precocious puberty is sometimes clinically evident when accompanied by visual disturbances or by raised intracranial pressure. It may be suspected in the presence of accelerated puberty but should also be feared in cases of apparently idiopathic precocious puberty. In the 13 cases studied, the tumour was studied in the posterior hypothalamus. Ten children underwent surgery (with additional radiotherapy in two cases). Two children died, the follow-up varying at present between 2 and 12 years. Amongst the various tumours, the hamartoma has a special nature by virtue of slow or absence of increase in tumour size. When the clinical and radiological signs suggest this type of tumour, abstention from surgery with close observation of the size of the tumour and medical slowing of puberty is advised.

A pair of micropellets of a 1% or 10% estradiol (E2)-paraffin mixture (containing 0.2 or 2 mug E2, respectively) or paraffin alone were implanted subcutaneously or intracerebrally in 5-day-old female rats. Animals given 10% E2 pellets became sterilized regardless of loci of the pellets. Of those which had received 1% E2 pellets, only animals with micropellets in the anterior hypothalamus became sterilized. It is suggested that neuronal components which are affected irreversibly by neonatal estrogen treatment are localized in the anterior hypothalamus.