The pharmacology of fever

The ability to minimise, if not prevent, large variations in deep body temperature that would otherwise result from some environmental conditions is a homeostatic function of unquestioned benefit that is demonstrated only by the more highly evolved animals. Nevertheless, body temperature is raised above normal values in many pathological conditions. This increase in temperature or fever is an active and co-ordinated response, which indicates the involvement of the CNS. Central injection and lesion studies have shown that the brain, in particular the PO/AH, is the site of action of fever-inducing agents, termed pyrogens. Electrophysiological data show that pyrogens modify the activity of central thermosensitive neurones as if to increase heat gain and decrease heat loss. The common response of fever to pyrogens of diverse origins is attributable to fever being mediated by an endogenous pyrogen released by phagocytic cells in the host. The mechanism by which central neuronal function is disturbed by pyrogens present in the periphery is not known. Tracer studies have yet to demonstrate the passage of a pyrogen across the blood-brain barrier. The possible involvement of several putative neuro- transmitters and modulators in fever has been reviewed here, but most compounds have not been studied sufficiently to allow firm conclusions to be drawn. Much of the data is limited to the effects of the putative mediators on normal thermoregulation but, even when the effect is hyperthermia, such observations do not necessarily indicate a role for the endogenous material in fever. Dose-response curves for agonists and the effects of antagonists are often undetermined. This shortfall in data is due to some extent to the nature of fever; a central response in vivo over several hours. Although fever may enhance other host reactions to combat infection and inflammation, neither this benefit nor the undesirability of antipyretic therapy has been demonstrated unequivocally in either homeothermic laboratory animals or humans. Consequently, antipyretic drugs continue to be used clinically to alleviate the fever, malaise and/or pain commonly associated with disease. The drugs in common usage are the nonsteroidal antipyretic analgesics, many of which also have an anti-flammatory effect. The primary mode of action of these drugs as antipyretics appears at present to be the inhibition of cyclo-oxygenase and a consequent reduction of prostanoid material in pyrogen-sensitive areas of the brain. PGEs in the PO/AH have received most study to date, but other mediators in other parts of the CNS, where the density of pyrogen receptors may be sparse, cannot be discounted and await further investigation.     

Projections of the temporo-parietal cortex on vestibular complex in the macaque monkey (Macaca fascicularis)

Summary Connections of the posterior parietal cortex (area 7) with the vestibular complex have been studied in 4 macaque monkeys by anterograde axonal transport methods. WGA-HRP and tritiated amino-acids have been injected in the posterior part of area 7 including the caudal end of the superior bank of superior temporal sulcus and the lateral sulcus. Labeled terminals were observed in the vestibular nuclei complex and distributed bilaterally with a greater ipsilateral contribution. Two main groups of area 7 efferences were found to project to vestibular complex: a) A first group terminates on vestibular nuclei (the inferior vestibular nucleus and the caudal part of the medial nucleus) mainly connected with cerebello-spinal system, b) A second group terminates on vestibular nuclei (the medial and the superior vestibular nuclei and the y group) mainly involved in vestibulo-ocular mechanisms. The prepositus hypoglossi nucleus has also been found to receive area 7 projections. It is concluded that the possible control played by area 7 on the vestibulo-ocular reflex might be exerted through these direct cortico-vestibular projections.     

Properties and localization of the anterior semicircular canal-activated vestibulocollic neurons in the cat

Summary Unit activites of secondary vestibular neurons that selectively responded to stimulation of the anterior semicircular canal nerve (ACN) were recorded extracellularly in the anesthetized cat. Axonal pathways and projections in the spinal cord of the ACN-activated neurons were examined by recording their antidromic responses to stimulation of the lateral and medial vestibulospinal tracts (LVST and MVST), and the bilateral neck extensor motoneuron pools in the C₁segment (C₁dorsal rami [DR] motoneuron pools). In order to determine whether the neurons had ascending axon collaterals to the extraocular motoneurons, the contralateral (c-) inferior oblique (IO) motoneuron pool was also stimulated. Twenty-seven neurons sent their axons to the ipsilateral (i-) C₁DR motoneuron pool via the LVST without any projection to the extraocular motoneuron pool. All the cells except one were located in the ventral part of the lateral vestibular nucleus. This pathway produced monosynaptic EPSPs with short time-to-peak and short half-width in C₁DR motoneurons (16/16 motoneurons). Eight neurons sent axons to the i-C₁DR motoneuron pool via the MVST without any to the extraocular motoneuron pool. Cell somata were located in the descending nucleus or in the ventral part of the lateral nucleus. These neurons did not produce postsynaptic potentials (PSPs) in any C₁DR motoneurons. All thirty-five neurons sending axons to the c-C₁DR motoneuron pool have ascending axon collaterals to the c-IO motoneuron pool.     

Phase shifts of circadian rhythms in activity entrained to food access

Rats anticipate daily 2 hr meals with a sharp increase in activity several hours prior to food availability. The present experiment examined the response to phase shifts of food access in rats with lesions of the suprachiasmatic nuclei (SCN). Following entrainment of activity to 2 hr of food per day, food access was phase delayed or phase advanced by 4, 6, or 8 hr. All rats responded to phase delays of 4 or 6 hr with an increase in the duration of anticipatory activity so that transients appeared mostly in activity onset. Following 8 hr phase delays, clear delaying transients in both activity onset and end were observed. Only a few rats showed advancing transients in activity after phase advances of food access. In response to 6 hr and 8 hr phase advances, 3 different responses occurred: (a) activity re-entrained to food access by the 2nd or 3rd day without clear intervening transients, (b) activity phase shifted by means of distinct delaying transients and (c) delaying transients occurred in one component of activity while a second component of activity appeared at the new phase position by the second or third day. These results provide further evidence that anticipation of food access is mediated by a circadian mechanism which is functionally independent of the SCN and illustrate some similarities as well as considerable differences between circadian rhythms entrained by feeding and those entrained by light-dark cycles.     

Cadherins in the central nervous system

The central nervous system (CNS) is divided into diverse embryological and functional compartments. The early embryonic CNS consists of a series of transverse subdivisions (neuromeres) and longitudinal domains. These embryonic subdivisions represent histogenetic fields in which neurons are born and aggregate in distinct cell groups (brain nuclei and layers). Different subsets of these aggregates become selectively connected by nerve fiber tracts and, finally, by synapses, thus forming the neural circuits of the functional systems in the CNS. Recent work has shown that 30 or more members of the cadherin family of morphoregulatory molecules are differentially expressed in the developing and mature brain at almost all stages of development. In a regionally specific fashion, most cadherins studied to date are expressed by the embryonic subdivisions of the early embryonic brain, by developing brain nuclei, cortical layers and regions, and by fiber tracts, neural circuits and synapses. Each cadherin shows a unique expression pattern that is distinct from that of other cadherins. Experimental evidence suggests that cadherins contribute to CNS regionalization, morphogenesis and fiber tract formation, possibly by conferring preferentially homotypic adhesiveness (or other types of interactions) between the diverse structural elements of the CNS. Cadherin-mediated adhesive specificity may thus provide a molecular code for early embryonic CNS regionalization as well as for the development and maintenance of functional structures in the CNS, from embryonic subdivisions to brain nuclei, cortical layers and neural circuits, down to the level of individual synapses.     

Clinical and electroencephalographic changes in MMP+-induced parkinsonian syndrome in rats

Laboratory of General Pathology of the Nervous System, Research Institute of General Pathology and Pathological Physiology, Academy of Medical Sciences of the USSR. Laboratory of Psychopharmacology and Group for Synthesis of Physiologically Active Compounds, Research Institute of Pharmacology, Academy of Medical Sciences of the USSR, Moscow. Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 107, No. 2, pp. 147–150, February, 1989.     

Body weight regulation in ground squirrels and hypothalamically lesioned rats: slow and sudden set point changes

Golden-mantled ground squirrels. Citellus lateralis, have a near annual cycle in body weight. In the present experiments their weights were temporarily forced off the usual levels either by food deprivation during a phase of weight gain or by offering extra palatable food during a phase of weight loss. When these treatments ceased the weights returned to levels appropriate for that time of year rather than to pretreatment values. Therefore the cycle of body weight in uniform and ad lib conditions reflects an underlying cycle in slowly climbing or sliding set points for body weight. In contrast to fattening ground squirrels, lesioned rats in the dynamic phase of hypothalamic hyperphagia did not compensate well for weight losses incurred during food deprivation. Weight gain during the dynamic phase appears to be roughly proportional to the discrepancy between actual and set weights, the latter being suddenly much elevated by the lesion.     

Quantitative Characterization of the Cellular Elements of Human Cerebellar Nuclei at Different Ages

A quantitative assessment of the cellular elements present in the nuclei of the human cerebellum was performed using subjects aged 22-90 years. A series of horizontal sections of cerebellar nuclei was studied. stained with hematoxylin and eosin. The numbers of neurons and gliocytes per unit area were measured on sections, with subsequent calculation of their ratios (the glial index). These experiments showed that aging is associated with decreases in the content of neurons and increases in the content of gliocytes. The extent of these changes increases as ontogenesis proceeds.     

Psammoma bodies and optically clear nuclei in bronchiolo-alveolar cell carcinoma. Diagnosis by fine needle aspiration biopsy with histologic and ultrastructural confirmation

The fine needle aspiration cytology of two cases of bronchiolo-alveolar cell carcinoma of the lung having unusual features is reported. One case demonstrated numerous psammoma bodies in the cytologic smears, whereas the other case showed an abundance of cells with optically clear nuclei. Both peripherally located tumors were resected and confirmed as primary bronchiolo-alveolar cell carcinoma by histologic and ultrastructural examination. We believe this to be the first report describing these unusual features of bronchiolo-alveolar cell carcinoma diagnosed by fine needle aspiration cytology. Presented is a discussion of psammoma bodies and optically clear nuclei seen in primary and metastatic tumors of the lung. This will aid in the diagnosis of these cases.