Publications

dynamics of sleep-wake cyclicity across the fetal period in sheep (ovis aries).	all adult mammals examined thus far exhibit sleep bout durations that follow an exponential distribution and wake bout durations that follow a power-law distribution. in altricial rodents such as rats and mice, exponential distributions of sleep bouts are found soon after birth, but the power-law distribution of wake bouts does not emerge until the third postnatal week. also, both sleep and bouts consolidate across the early postnatal period. it is not known whether similar developmental process ...	2011	20886534
maturational changes and effects of chronic hypoxemia on electrocortical activity in the ovine fetus.	we have studied the maturation of electrocortical (ecog) activity in fetal sheep and the impact of chronic hypoxemia using a growth restriction model with placental embolizations. twenty chronically catheterized fetal sheep (control, n=9; hypoxemic, n=11) were monitored at 116-119, 121-126 and 128-134 days gestational age (term=145 days), with ecog activity scored using automated analysis of amplitude and frequency components to distinguish low-voltage/high frequency (lv/hf) and high-voltage/low ...	2011	21683944
cerebral sympathetic nerve activity has a major regulatory role in the cerebral circulation in rem sleep.	sympathetic nerve activity (sna) in neurons projecting to skeletal muscle blood vessels increases during rapid-eye-movement (rem) sleep, substantially exceeding sna of non-rem (nrem) sleep and quiet wakefulness (qw). similar sna increases to cerebral blood vessels may regulate the cerebral circulation in rem sleep, but this is unknown. we hypothesized that cerebral sna increases during phasic rem sleep, constricting cerebral vessels as a protective mechanism against cerebral hyperperfusion durin ...	2009	19150858
atypical scrapie in sheep from a uk research flock which is free from classical scrapie.	in the wake of the epidemic of bovine spongiform encephalopathy the british government established a flock of sheep from which scrapie-free animals are supplied to laboratories for research. three breeds of sheep carrying a variety of different genotypes associated with scrapie susceptibility/resistance were imported in 1998 and 2001 from new zealand, a country regarded as free from scrapie. they are kept in a purpose-built sheep unit under strict disease security and are monitored clinically an ...	2009	19208228
sympathetic withdrawal augments cerebral blood flow during acute hypercapnia in sleeping lambs.	cerebral sympathetic activity constricts cerebral vessels and limits increases in cerebral blood flow (cbf), particularly in conditions such as hypercapnia which powerfully dilate cerebral vessels. as hypercapnia is common in sleep, especially in sleep disordered breathing, we tested the hypothesis that sympathetic innervation to the cerebral circulation attenuates the cbf increase that accompanies increases in paco2 in sleep, particularly in rem sleep when cbf is high.	2008	19090329
coronary blood flow becomes uncoupled from myocardial work during obstructive sleep apnea in the presence of endothelial dysfunction.	patients with obstructive sleep apnea (osa) and coronary artery disease have a poor long-term prognosis. it is unknown whether the coronary blood flow (cbf) response to osa is appropriate for myocardial metabolic requirements. therefore, cbf was assessed during osa, before and after the development of coronary artery endothelial dysfunction.	2008	18548825
onset of feeding at birth--perinatal development of the hypothalamic mechanisms that induce appetite and feeding in the newborn.	orexin-a and -b are hypothalamic peptides which, in the adult brain, are associated with arousal, increased vigilance, and the seeking and ingestion of food. because the fetus is mostly asleep, and hunger is a physiological state unlikely to arise until birth, we hypothesized that orexigenic neurons in the lateral and dorso-medial hypothalamic areas (lha, dmh) and their projections to the locus coeruleus (lc) would develop only near the time of birth. we therefore determined orexin expression in ...	2008	18395343
animal models of human placentation--a review.	this review examines the strengths and weaknesses of animal models of human placentation and pays particular attention to the mouse and non-human primates. analogies can be drawn between mouse and human in placental cell types and genes controlling placental development. there are, however, substantive differences, including a different mode of implantation, a prominent yolk sac placenta, and fewer placental hormones in the mouse. crucially, trophoblast invasion is very limited in the mouse and ...	2007	17196252
fluoxetine during pregnancy: impact on fetal development.	women are at greatest risk of suffering from depression during the childbearing years and thus may either become pregnant while taking an antidepressant or may require a prescription for one during pregnancy. the antidepressant fluoxetine (fx) is a selective serotonin reuptake inhibitor (ssri), which increases serotonin neurotransmission. serotonin is involved in the regulation of a variety of physiological systems, including the sleep-wake cycle, circadian rhythms and the hypothalamic-pituitary ...	2005	16263070
sympathetic nervous control of the cerebral circulation in sleep.	cerebral vessels are extensively innervated by sympathetic nerves arising from superior cervical ganglia, and these nerves might play a protective role during the large arterial pressure surges of active sleep (as). we studied lambs (n=10) undergoing spontaneous sleep-wake cycles before and after bilateral removal of the superior cervical ganglia (scgx, n=5) or sham ganglionectomy (n=5). lambs were instrumented to record cerebral blood flow (cbf, flow probe on the superior sagittal sinus), carot ...	2005	16120102
autoregulation of the cerebral circulation during sleep in newborn lambs.	autoregulation is a vital protective mechanism that maintains stable cerebral blood flow as cerebral perfusion pressure changes. we contrasted cerebral autoregulation across sleep-wake states, as little is known about its effectiveness during sleep. newborn lambs (n= 9) were instrumented to measure cerebral blood flow (flow probe on the superior sagittal sinus) and cerebral perfusion pressure, then studied during active sleep (as), quiet sleep (qs) and quiet wakefulness (qw). we generated cerebr ...	2005	15760939
cerebral blood flow during spontaneous and cholinergically induced behavioral states in the sheep fetus.	the sleep-wake cycle has been studied extensively in both adult and fetal mammalian species with emphasis in different areas. fetal studies have focused on characterization of behavioral states and responses to challenges such as hypoxia, and there have been relatively fewer studies that have investigated the control of fetal behavioral state. the objective of this study was to determine whether cerebral blood flow during cholinergically induced fetal behavioral states was similar to that during ...	2005	15718367
sleep-dependent changes in the coupling between heart period and arterial pressure in newborn lambs.	this study assessed whether sleep-dependent changes in the relationship between heart period (hp) and mean arterial pressure (map) occur in newborn life. electrodes for electrocorticographic, electromyographic, and electrooculographic monitoring and an arterial catheter for blood pressure recordings were implanted in 11 newborn lambs. hp and map beat-to-beat values were computed from 120-s blood pressure recordings during quiet wakefulness, active sleep, and quiet sleep. for each recording, the ...	2005	15531745
[functional risk assessment of handling of sheep housing and pasture areas at a scrapie-infested farm in mecklenburg-west pomerania].	in the wake of a scrapie monitoring programme 2002 in mecklenburg-westpomerania a total of 10 positive cases were identified after culling at a suffolk-farm with about 1000 animals. scientific based recommendations are difficult to judge as longitudinal studies and subsequent quantitative risk factors regarding the epidemiology of scrapie are either not available or conflicting. given this background a risk assessment was developed that is based on the probability of validated risk factors consi ...	2004	15188682
sleep-related changes in the regulation of cerebral blood flow in newborn lambs.	the interplay between cerebral perfusion pressure (cpp) and vascular resistance leads to fluctuations in cerebral blood flow (cbf). the relationship between fluctuations in cbf and those in cpp provides insight into the impact of the regulation of vascular resistance on cbf. the aim of this work was to study sleep-related changes in cbf regulation in newborn lambs, by quantifying the extent to which variability in cbf is related to that of cpp in the different wake-sleep states.	2004	14998235
prostaglandin d synthase in the prenatal ovine brain and effects of its inhibition with selenium chloride on fetal sleep/wake activity in utero.	it has been proposed that prostaglandin (pg) d(2) induces physiological sleep in mammals by acting on sleep centers located in the anterior hypothalamus. in fetal sheep, definitive rapid-eye-movement and non-rapid-eye-movement sleep states appear at approximately 125 d gestation (term is approximately 147 d). in adult animals, pgd synthase (pgds) (functionally and structurally homologous to beta-trace protein) is secreted into csf with a circadian pattern, with the highest concentrations present ...	2002	12097519
nitric oxide inhibition abolishes sleep-wake differences in cerebral circulation.	nitric oxide (no), being produced by active neurones and also being a cerebral vasodilator, may couple brain activity and blood flow in sleep, particularly during active sleep (as), which is characterized by widespread neural activation and markedly elevated cerebral blood flow (cbf) compared with quiet wakefulness (qw) and quiet sleep (qs). this study examined cbf and cerebral vascular resistance (cvr) in lambs (n = 6) during spontaneous sleep-wake cycles before and after infusion of n(omega)-n ...	2001	11356615
the relationship of lymphocytes in blood and in lymph to sleep/wake states in sheep.	based on evidence of a role for immune-associated cytokines in sleep induction, we investigated the possibility that lymphocyte distribution between blood and lymphatics could be altered as a function of sleep/wakefulness. blood and lymph sample were obtained from 5 sheep during periods of slow-wave sleep and wake. blood and lymph lymphocytes were phenotyped using monoclonal antibodies against cd4, cd8, gd t-cell receptors and a surface marker on ovine b cells. lymph flow rates and efferent lymp ...	2000	10737335
effect of pregnane steroids on electrocortical activity and somatosensory evoked potentials in fetal sheep.	the effect of infusing the neuroactive steroids pregnanolone and iso-pregnanolone on somatosensory evoked potentials (sep) and electrocortical (ecog) activity was studied in unanaesthetised fetal sheep, 130-135 days gestation. intravenous infusion of pregnanolone (6 mg/kg per h) significantly increased the proportion of high voltage ecog (56.1+/-4.8% vs. control 43.5+/-3.2%, p < 0.05), and decreased low voltage ecog (43.9+/-4.8% vs. control 56.6+/-3.2%, p < 0.05). pregnanolone treatment decrease ...	1998	9774162
follicle-stimulating hormone is secreted more irregularly than luteinizing hormone in both humans and sheep.	recently introduced statistical tools capable of discerning differences between the pattern of luteinizing hormone (lh) secretion and that of follicle-stimulating hormone (fsh) could be valuable in understanding ovulation and menopause, and ultimately in making diagnostic decisions and treating infertility and polycystic ovary syndrome. we assessed the validity and scope of the hypothesis that fsh is secreted more irregularly than lh in ewes and fertile women. we compared secretory irregularity ...	1998	9502773
suppression of arousal by progesterone in fetal sheep.	the high rate of progesterone synthesis by the placenta in late gestation exposes the ovine fetus to high concentrations of progesterone and its metabolites that may affect activity of the fetal brain. the aim of this study was to determine the effect of inhibiting maternal progesterone synthesis on sleep-wake activity in fetal sheep. fetal and maternal vascular catheters, a fetal tracheal catheter, and electrodes for recording fetal electrocortical (ecog), electro-ocular (eog) and nuchal muscle ...	1997	9733059
influence of sedation on arousal and cardiorespiratory responses to airflow obstruction in sleeping lambs.	our aim was to determine the effects of two commonly used sedatives, promethazine and diazepam, on arousal and cardiorespiratory responses to airflow obstruction in sleeping lambs. in eight lambs fitted with obstructable rubber face masks, we recorded electrocortical, electroocular, and electromyographic activities to identify sleep-wake states; intrapleural pressure, heart rate, and percentage o2 saturation (sao2) were also recorded. in each lamb, arousal and respiratory responses were measured ...	1996	8888284
continuous measurement of blood flow in the superior sagittal sinus of the lamb.	we assessed the validity of recording blood flow in the superior sagittal sinus (qss) as a measure of cerebral blood flow (cbf). while anesthetized, 10 lambs were instrumented with a transit-time ultrasonic flow probe around the superior sagittal sinus to measure qss, electrodes to assess sleep state, catheters to measure cerebral perfusion pressure (pcp), and an occlusive cuff around the common brachiocephalic artery to vary blood pressure. after 72 h recovery, lambs were studied during spontan ...	1995	7653647
the biology and molecular biology of scrapie-like diseases.	the transmissible spongiform encephalopathies (tse's) are degenerative diseases of the central nervous system which naturally affect man (creutzfeldt-jakob disease [cjd], gerstmann-sträussler syndrome [gss], kuru), sheep and goats (scrapie), cattle (bovine spongiform encephalopathy [bse]), mink (transmissible mink encephalopathy), mule deer, elk and antelope (chronic wasting disease). spongiform encephalopathies have also been diagnosed in captive species of zoo antelope and in domestic cats. mu ...	1993	8219804
sustained vortex-like waves in normal isolated ventricular muscle.	sustained reentrant excitation may be initiated in small (20 x 20 x less than 0.6 mm) preparations of normal ventricular muscle. a single appropriately timed premature electrical stimulus applied perpendicularly to the wake of a propagating quasiplanar wavefront gives rise to circulation of self-sustaining excitation waves, which pivot at high frequency (5-7 hz) around a relatively small "phaseless" region. such a region develops only very low amplitude depolarizations. once initiated, most epis ...	1990	2247448
prenatal morphine exposure and sleep-wake disturbances in the fetus.	we have previously shown that acute exposure to low-dose morphine stimulates arousal and breathing movements in the fetal lamb. we now report on the effects of subacute low-dose morphine exposure on the regulation of fetal sleep-wake behavior and breathing patterns. morphine was infused to 11 fetal lambs (121-129 days gestation) at a constant rate of 400 micrograms/h for 7 days via a mini osmotic pump implanted subcutaneously in the maternal flank and connected directly to an indwelling catheter ...	1988	3381053
cholinergic influences on sleep-wake patterns and breathing movements in the fetus.	fetal lambs were prepared for chronic intrauterine recording of behavioral states and breathing movements during the third trimester of pregnancy. pilocarpine administered directly to the fetus produced an immediate change from quiet sleep to arousal. neither the time spent in rapid eye movement (rem) sleep nor the latency to rem sleep was affected. associated with this change in sleep-wake patterns, pilocarpine produced a dose-dependent increase in the incidence of fetal breathing movements. th ...	1988	3171982
prenatal development of sleep-wake patterns in sheep.	chronic intrauterine monitoring of electrocortical activity, eye movements, and electromyographic activity of the nuchal muscles has permitted the use of established polygraphic criteria to study the ontogenetic development of organized sleep-wake patterns in the fetal lamb in utero. sixty-five polygraphic recordings obtained from 21 fetal lambs ranging from 112 to 144 days of gestation (term = 145 days) were analyzed. the results show that the transition from disorganized to organized behaviora ...	1985	3880175
co2 and naloxone modify sleep/wake state and activate breathing in the acute fetal lamb preparation.	we studied locally anesthetized lamb fetuses (140-144 days' gestation) in utero on the day of surgical preparation (the acute preparation) to correlate sleep/wake (s/w) states with fetal breathing movements (fbm) activated by co2 with and without endorphin displacement by naloxone. we placed electrodes for definition of s/w states, a carotid arterial catheter for injections and measurements of pressure, pha, paco2 and pao2, and intratracheal and intraesophageal catheters for measurement of fbm a ...	1984	6429803
effect of temperature on regulation of breathing and sleep/wake state in fetal lambs.		1983	6403494