Hyperthermia exacerbates ischaemic brain injury.

Hyperthermia frequently occurs in stroke patients. Hyperthermia negatively correlates with clinical outcome and adversely effects treatment regiments otherwise successful under normothermic conditions. Preclinical studies also demonstrate that hyperthermia converts salvageable penumbra to ischaemic infarct. The present article reviews the knowledge accumulated from both clinical and preclinical studies about hyperthermia and ischaemic brain injury, examines current treatment strategies and discusses future research directions.

Hormones and honest signals: males with larger ornaments elevate testosterone more when challenged.

When male investment in mating varies with quality, reliable sexual signals may evolve. In many songbirds, testosterone mediates mating investment, suggesting that signals should be linked to testosterone production. However, because testosterone may change rapidly during behaviour such as territorial aggression and courtship, efforts to establish such a relationship have proved challenging. In a population of dark-eyed juncos, we measured individual variation in the production of short-term testosterone increases by injecting gonadotropin-releasing hormone (GnRH). We found a positive correlation between the magnitude of these increases and the size of a plumage ornament ('tail white') previously shown to be important for female choice and male-male competition. We then measured naturally elevated testosterone levels produced during male-male competition and found that they covaried with those induced by GnRH. We suggest that the association between tail white and testosterone increases may allow conspecifics to assess potential mates and competitors reliably using tail white.

Basic and advanced life support, acute resuscitation, and cardiac resuscitation.

The global approach to resuscitation has changed dramatically in the past year. The groundwork for these changes began a decade ago with the development of the Utstein guidelines for uniform reporting of critical events. Consistency in data collection was necessary to enable evidence-based review and comparison of current practice. Resuscitation protocols have been significantly altered based upon these data. Basic life support (BLS) protocols have been simplified. Early access to electrical cardioversion is the key to survival. Mobilization of AED technology in the community is essential. Several issues were identified as crucial to future improvement of resuscitation statistics. Prevention strategies should be developed for high-risk patients. There is a need to identify cases in which resuscitation should not be started. Enhancement of educational methods to improve performance and retention of skills is key. Finally, the roadblocks for performance of ethical prospective research must be minimized.

Steroid hormones and immune function: experimental studies in wild and captive dark-eyed juncos (Junco hyemalis).

Monogamous and polygynous male songbirds generally differ in their breeding season profiles of circulating testosterone. Testosterone level spikes early in the breeding season of monogamists and then declines, but it remains high in polygynists. Male dark-eyed juncos (Junco hyemalis) are socially monogamous and exhibit the usual pattern, but experimental maintenance of high testosterone throughout the breeding season alters normal behavior and physiology and affects various components of annual reproductive success but not overall annual success. Because stabilizing selection predicts that alteration of naturally existing phenotypes should reduce lifetime reproductive success, we asked whether prolonged testosterone exposure might impair immune function and perhaps thereby reduce life span. We assessed immune function in captive and wild male juncos that we treated with either testosterone-filled or empty Silastic implants. Results indicate that prolonged elevation of testosterone suppresses antibody production in captive males and cell-mediated immunity in wild males. Together these results suggest that testosterone-treated males may be more susceptible to disease or parasitic infection. As earlier studies have shown, levels of corticosterone as well as testosterone are higher in testosterone-treated males, so it is unclear whether the immune suppression we observed is due to testosterone's direct effects on immunity or testosterone's influence on glucocorticoid production. We discuss results in the context of recent hypotheses regarding life-history theory and potential endocrine-immune interactions.

Effects of captivity and testosterone on the volumes of four brain regions in the dark-eyed junco (Junco hyemalis).

This study investigates the effects of captivity and testosterone treatment on the volumes of brain regions involved in processing visual and spatial information in adult dark-eyed juncos (Junco hyemalis). We treated captive and free-living male juncos with either testosterone-filled or empty implants. Captive juncos had a smaller hippocampal formation (HF) (both in absolute volume and relative to telencephalon) than free-living birds, regardless of hormone treatment. Testosterone-treated males (both captive and free-living) had a smaller telencephalon and nucleus rotundus, but not a smaller HF or ectostriatum, than controls. We found that free-living testosterone-treated males had larger home ranges than free-living controls in agreement with earlier experiments, but we found no corresponding difference in HF volume. We discuss the implications of the effect of captivity on HF volume for past and future laboratory experiments.

Egg yolk layers vary in the concentration of steroid hormones in two avian species.

Maternally derived steroid hormones are known to be present in the yolks of avian eggs; however, the physiological mechanisms involved in their deposition remain largely unexplored. Investigations of steroid production by avian follicles have demonstrated temporal differences in the concentrations of progesterone, 17beta-estradiol, and testosterone during yolk formation. Because yolk is deposited peripherally in concentric spheres as the oocyte develops, differences in the production of follicular hormones during yolk formation should be manifested in differences in the localization of steroids within layers of the yolk. To investigate this hypothesis we analyzed steroid hormone concentrations in layers of individual eggs of the dark-eyed junco (Junco hyemalis) and the red-winged blackbird (Agelaius phoeniceus). We found that in the dark-eyed junco the concentration of progesterone is significantly greater at the periphery of the yolk, while the concentration of 17beta-estradiol is significantly greater near the center of the yolk. We also found in both the dark-eyed junco and the red-winged blackbird that the concentration of testosterone remains constant from the interior to the intermediate layers of the yolk and then drops sharply between the intermediate and exterior layers. The patterns of hormone localization that we found agree with those predicted by studies of temporal changes in steroidogenesis in the maturing follicle of the chicken, thus suggesting that within-yolk variation in yolk steroid concentrations in the dark-eyed junco and the red-winged blackbird reflects temporal differences in the pattern of follicular steroidogenesis. Variation in the concentration of hormones among yolk layers presents a methodological concern for studies that involve the removal of yolk samples from viable eggs for subsequent hormonal analysis. This variation also has implications for the timing of embryonic exposure to steroid hormones.

Early administration of 17beta-estradiol partially masculinizes song control regions and alpha2-adrenergic receptor distribution in European starlings (Sturnus vulgaris).

The vocal control system in many songbird species is a sexually dimorphic neural circuit that mediates learning and production of song. The mechanism by which this system is sexually differentiated has been investigated in only one species, the zebra finch (Taeniopygia guttata). Estradiol may be involved in the sexual differentiation of this system, as female zebra finches treated with estradiol as nestlings develop a male-like song system; however, blocking estradiol action in embryonic and nestling male zebra finches does not demasculinize the song system. Therefore, the role of estradiol in song system development is unclear. The role of estradiol in song system sexual differentiation was assessed in European starlings (Sturnus vulgaris). This species is of potential interest because it is less extreme in the degree of sexual dimorphism of the song system and song behavior than zebra finches. While in the field, starling nestlings were implanted with 500 microg of estradiol at 3 days of age. These birds were brought into the laboratory at Day 11 and hand-reared. In females, estradiol produces significant increases in the volumes of song control regions defined by Nissl stain, as well as by autoradiography for alpha2-adrenergic receptors; however, these estradiol-treated females have song systems that more closely resemble those of control females than control males. Estradiol-treated males exhibit significant hypermasculinization at 210 days of age, but this effect is transient and hypermasculinization is no longer evident at Day 345. The role of estradiol in sexual differentiation of the neural circuit mediating song behavior remains enigmatic.

Autoradiographic localization of D1-like dopamine receptors in the forebrain of male and female Japanese quail and their relationship with immunoreactive tyrosine hydroxylase.

The distribution of D1-like dopamine receptors was studied in the brain of male and female Japanese quail (Coturnix japonica) by means of quantitative autoradiography with 3H-labelled D1 selective antagonist, SCH 23390, serving as a ligand. A specific, saturable, high affinity binding of this ligand was demonstrated. High densities of binding sites were detected in the lobus parolfactorius, olfactory tubercle, and paleostriatum augmentatum. Medium densities were observed in the entire neostriatum and in the external layers of the optic tectum. Similar levels of binding outlined the paleostriatum primitivum, the nucleus pretecalis and the nucleus intercollicularis. Low but significant levels of receptors were also present in the medial preoptic area at the level of the sexually dimorphic medial preoptic nucleus and throughout the infundibulum, as well as in the ectostriatum, medial and lateral septum, and nucleus accumbens. At the level of the medial septum, just dorsal to the anterior commissure, two circular areas of high receptor density corresponding to the nucleus of the septal commissure were also observed. No sex difference in receptor density could be detected in any of the areas. All areas containing high densities of D1 receptors also contained high densities of tyrosine hydroxylase (TH) fibers. However, certain areas characterized by a high density of TH-immunoreactive fibers did not contain appreciable densities of D1-like dopamine receptors. The distribution of this receptor and its relationship to TH-immunoreactivity is consistent with observations made in other vertebrates, suggesting that the dopaminergic system is evolutionarily highly conserved among amniote vertebrates.

Characterization and localization of D1 dopamine receptors in the sexually dimorphic vocal control nucleus, area X, and the basal ganglia of European starlings.

D1 dopamine receptors were pharmacologically characterized and localized by quantitative autoradiography in the basal ganglia of male and female European starlings (Sturnus vulgaris). The D1 selective antagonist SCH 23390 was used to label this receptor subtype. Starlings are songbirds and possess a neural circuit implicated in the learning and production of song. This circuit includes a sexually dimorphic nucleus, area X, that is a subregion of the parolfactory lobe of the basal ganglia and is known from work on zebra finches to receive dopaminergic input from the area ventralis of Tsai. We focused our investigation on the D1-like receptor subtype because they are abundant in the basal ganglia. Competition studies indicate that a variety of dopaminergic ligands compete with [3H] SCH 23390 for the binding site in an order of potency characteristic of a D1-like receptor. Autoradiographic studies of the basal ganglia revealed high D1 receptor densities in the avian homologues of the caudate-putamen and relatively low-receptor densities were observed in the avian homologue of the globus pallidus. In male starlings, area X could be reliably discerned on the autoradiograms by the higher density of D1 receptors compared to the surrounding parolfactory lobe (LPO). This was also true for females, though not as reliably as in males. When we compared the mean D1 receptor density in area X for males and females we did not find a significant sex difference. However, we also analyzed the data by comparing sex differences in the degree to which area X has a higher receptor density in comparison with the surrounding LPO. When we normalized D1 receptor density in area X relative to the LPO, we did find a significant sex difference. This sex difference in relative receptor density represents another neural sex difference in the song circuit that may mediate sex differences in the learning and production of song in starlings and other songbirds.

Sex differences in the volume of avian song control nuclei: comparative studies and the issue of brain nucleus delineation.

Two goals of research on neural sex differences are to establish the behavioral function of such sex differences and to identify precisely what features differ between males and females. Comparative studies of sex differences in the volume of brain nuclei within the songbird vocal control circuit provide one way to address these goals. Informative comparisons can be either inter-specific or intra-specific. Inter-specific comparisons of species within the songbird suborder allow one to establish how species variation in the degree to which there is a sex difference in nuclear volume relates to species variation in the degree to which there is a sex difference in vocal behavior. Intraspecific comparisons of sex differences in nuclear volume involve the comparison of a variety of histochemical methods to define nuclei and describe a nucleus within a species. Sex differences in nuclear volume have now been measured for at least some song control nuclei in 10 different passerine species. In species with more complex male than female song, the volume of key song control nuclei is on average larger in males than in females. However, future studies will require more refined measures of vocal behavior and perceptual abilities to make more precise correlations between brain and behavior. In European starlings (Sturnus vulgaris), the volume of the vocal control nucleus, area X was found to be on average 1.95 times bigger in males than in females based on Nissl stained sections. Variation in neurotransmitter receptor density as determined by quantitative receptor autoradiography can also be used to define clearly the boundaries of a nucleus. When the boundaries of area X in male and female starlings were defined based on variation in muscarinic cholinergic and alpha 2-adrenergic receptor densities, volumetric estimates were obtained that are nearly identical to those obtained with the use of Nissl stains. Intra-specific comparisons of this sort extend our knowledge concerning the neurochemical basis of sex differences in nuclear volume. The wide application of this method would greatly increase our understanding of neural sex differences.

Sexual dimorphism in the volume of song control nuclei in European starlings: assessment by a Nissl stain and autoradiography for muscarinic cholinergic receptors.

Previous studies have found that the volume of several song control nuclei is larger in male songbirds than in female songbirds. The degree of this volumetric sex difference within a given species appears to be systematically related to the degree of the behavioral sex difference. The largest volumetric differences have been reported in species in which the male sings and the female sings little, if at all, and the smallest sex differences in volume have been reported in species in which males and females both sing in nearly equal amounts. We compared the volume of three song control nuclei in male and female European starlings (Sturnus vulgaris), a species in which females are known to sing, though at a much lower rate than males. We investigated the volume of hyperstriatum ventrale, pars caudale, nucleus robustus archistriatalis, and area X of the lobus parolfactorius as defined with the use of a Nissl stain. In addition, we measured the volume of area X as defined by the density of muscarinic cholinergic receptors visualized by in vitro receptor autoradiographic methods. The volumes of all three of the song nuclei, as defined by Nissl staining, are significantly larger in males than in females. For area X, Nissl staining and receptor autoradiography indicate the same significant volumetric sex difference. The three nuclei are approximately one and one half to two times larger in males than in females, a degree of dimorphism that is intermediate to those reported for other species. Previous investigations of sex differences in the avian vocal control system have used only Nissl stains to define nuclear volumes. We demonstrate in this paper that receptor autoradiography can be used to assess dimorphisms in nuclear volume. Broad application of this approach to a number of neurotransmitter receptor systems will better characterize the dimorphisms in the song system, and therefore will provide greater insight into the neuroanatomical and neurochemical control of birdsong.

Prenatal flutamide alters sexually dimorphic nuclei in the spinal cord of male rats.

The effects of prenatal exposure to the antiandrogen flutamide on two sexually dimorphic nuclei of the lumbar spinal cord, the dorsolateral nucleus (DLN) and the spinal nucleus of the bulbocavernosus (SNB), were investigated. Rat dams were given daily injections of 5 mg flutamide or vehicle alone from day 11 through 21 of pregnancy. The spinal cords and perineal morphology of their male and female offspring were examined in adulthood. Flutamide reduced the number of SNB and DLN neurons, reduced the somal and nuclear area of SNB neurons, and reduced the weight of the perineal muscles in males. Flutamide produced no effect in females. No sexual dimorphism was found in the mean somal area of DLN neurons, but a sexual dimorphism was found in the distribution of somal areas in our samples; females had proportionately more large neurons than males. Flutamide-treated males also had proportionately more large neurons than control males but fewer than females. A sexual dimorphism was found in the nuclear areas of DLN neurons but flutamide did not influence this trait.

Deoxyribonucleoprotein complexes and DNA synthesis of herpes simplex virus type 1.

Two temperature-sensitive mutants of herpes simplex virus type 1 in complementation group 1-1 were analyzed to determine if the major DNA-binding protein they produced was thermolabile. Cells infected with these mutants were analyzed for deoxyribonucleoprotein complexes containing the DNA-binding protein. These complexes were found in cells infected at the permissive temperature but not at the nonpermissive temperature. In temperature shift-up experiments with mutant virus infected cells, the levels of the deoxyribonucleoprotein complexes decreased with time of incubation at the nonpermissive temperature. Viral DNA synthesis terminated in cells infected with these mutants after temperature shift-up. The kinetics of termination of viral DNA synthesis were similar to the kinetics of dissociation of the deoxyribonucleoprotein complexes. These results indicate that two mutants in complementation group 1-1 produce a thermolabile DNA-binding protein and that this protein is required for viral DNA synthesis. Furthermore, they suggest that the major DNA-binding protein of herpes simplex virus type 1 functions in viral DNA synthesis as a component of deoxyribonucleoprotein complexes.

Identification and characterization of deoxyribonucleoprotein complexes containing the major DNA-binding protein of herpes simplex virus type 1.

Nuclear extracts were prepared from cells infected with herpes simplex virus type 1 (HSV-1) and fractionated by sucrose gradient centrifugation to identify deoxyribonucleoprotein complexes involved in viral replication. Large amounts of an HSV-1 induced protein with a molecular weight of about 133,000 sedimented as a broad peak in the 25 S region of the gradient and cosedimented with 13 S DNA fragments. The sedimentation of both the protein and DNA decreased upon treatment of nuclear extracts with DNase. This result indicated that the protein and DNA were associated in deoxyribonucleoprotein complexes. The protein was identified as the HSV-encoded major DNA-binding protein ICP8 based on its molecular weight, its association with DNA in nuclear extracts, and its immunoprecipitation with monospecific antiserum and monoclonal antibody to ICP8. Deoxyribonucleoprotein complexes containing ICP8 could be immunoprecipitated from nuclear extracts. When DNA was extracted from these immunoprecipitates, fractionated by agarose gel electrophoresis, transferred to nitrocellulose paper, and hybridized to 32P-labeled HSV-1 or cell DNA, both HSV-1 and cell DNA sequences were identified. Cesium chloride gradient analysis of the immunoprecipitated DNA indicated that duplex DNA was present in the complexes. Thus, the major DNA-binding protein of HSV-1 is associated with both duplex HSV-1 and cell DNA in vivo.