Hypocretins, sleep, and maternal behavior.

The postpartum period is a demanding time during which mothers experience numerous physiological adaptations that enable them to care for their offspring while maintaining their wellbeing. Hypocretins, also known as orexins, are neuropeptides synthesized by hypothalamic neurons that play a fundamental role in several functions, including the promotion of wakefulness and motivated behaviors, such as maternal care. In this regard, several findings suggest that the activity of the hypocretinergic system increases in the early postpartum period and begins to decline as weaning approaches. In particular, hypocretins within the medial preoptic area, a crucial region during this period, modulate both maternal behavior and sleep. Although further studies are necessary to obtain a comprehensive understanding of the role of hypocretins in lactating females, current research suggests that this system participates in promoting active components of maternal behavior and regulating wakefulness and sleep adjustments during the postpartum period, potentially leading to increased wakefulness during this stage. These adaptive adjustments enable the mother to cope with the continuously changing demands of the pups.

Amygdala and hippocampus dialogue with neocortex during human sleep and wakefulness.

ABSTRACT: Previous studies have described synchronic electroencephalographic (EEG) patterns of the background activity that is characteristic of several vigilance states. STUDY OBJECTIVES: To explore whether the background synchronous activity of the amygdala-hippocampal-neocortical circuit is modified during sleep in the delta, theta, alpha, sigma, beta, and gamma bands characteristic of each sleep state. METHODS: By simultaneously recording intracranial and noninvasive scalp EEG (10-20 system) in epileptic patients who were candidates for neurosurgery, we explored synchronous activity among the amygdala, hippocampus, and neocortex during wakefulness (W), Non-Rapid Eye Movement (NREM), and Rapid-Eye Movement (REM) sleep. RESULTS: Our findings reveal that hippocampal-cortical synchrony in the sleep spindle frequencies was spread across the cortex and was higher during NREM versus W and REM, whereas the amygdala showed punctual higher synchronization with the temporal lobe. Contrary to expectations, delta synchrony between the amygdala and frontal lobe and between the hippocampus and temporal lobe was higher during REM than NREM. Gamma and alpha showed higher synchrony between limbic structures and the neocortex during wakefulness versus sleep, while synchrony among deep structures showed a mixed pattern. On the one hand, amygdala-hippocampal synchrony resembled cortical activity (i.e. higher gamma and alpha synchrony in W); on the other, it showed its own pattern in slow frequency oscillations. CONCLUSIONS: This is the first study to depict diverse patterns of synchronic interaction among the frequency bands during distinct vigilance states in a broad human brain circuit with direct anatomical and functional connections that play a crucial role in emotional processes and memory.

Effects of Cannabis Consumption on Sleep.

Despite the fact that medical properties of Cannabis have been recognized for more than 5000 years, the use of Cannabis for medical purposes have recently reemerged and became more accessible. Cannabis is usually employed as a self-medication for the treatment of insomnia disorder. However, the effects of Cannabis on sleep depend on multiple factors such as metabolomic composition of the plant, dosage and route of administration. In the present chapter, we reviewed the main effect Cannabis on sleep. We focused on the effect of "crude or whole plant" Cannabis consumption (i.e., smoked, oral or vaporized) both in humans and experimental animal models.The data reviewed establish that Cannabis modifies sleep. Furthermore, a recent experimental study in animals suggests that vaporization (which is a recommended route for medical purposes) of Cannabis with high THC and negligible CBD, promotes NREM sleep. However, it is imperative to perform new clinical studies in order to confirm if the administration of Cannabis could be a beneficial therapy for the treatment of sleep disorders.

Newborn infants who received skin-to-skin contact with fathers after Caesarean sections showed stable physiological patterns.

AIM: Separating infants and their parents after a Caesarean section is still the routine care worldwide. This study investigated three caregiving models on the wakefulness and physiological parameters of full-term infants after an elective Caesarean section. METHODS: Newborn infants born in a Chilean public hospital in 2009-12 were randomised to three groups: cot, fathers' arms or skin-to-skin contact with their father. They were assessed at 15-minute intervals, from 45 to 120 minutes after the Caesarean section. Their physiological parameters were measured, and their wakefulness was assessed using the Neonatal Behavioural Assessment Scale. RESULTS: We studied 95 infant (53% girls) born at a mean gestational age of 38.9 ± 0.9 weeks. Heart rates were significantly higher in the skin-to-skin than cot or fathers' arms groups and showed greater stability over time. Wakefulness was initially higher in the skin-to-skin group, but there were no significant differences by the end of the observation. There were no differences between the groups in peripheral oxygen saturation. Skin-to-skin contact had no negative impact on the infants. CONCLUSION: The skin-to-skin group showed some advantages over the cot and fathers' arms groups when it came to establishing stable physiological parameters and wakefulness. This approach should be supported during mother-infant separation.

Heart rate variability in frontal lobe epilepsy: Association with SUDEP risk.

OBJECTIVES: Frontal lobe epilepsy (FLE) may impair autonomic heart rate modulation. Decreased heart rate variability (HRV) may enhance risk of sudden death. Our objective was to describe whole day and wakefulness/sleep HRV parameters from FLE patients in comparison with those of healthy controls and correlate HRV parameters to SUDEP-7 scores. METHODS: Ten patients with FLE and 15 healthy controls underwent a 24-hour electrocardiogram holter. The SUDEP-7 score was calculated for patients. Subgroups were identified according to active epilepsy, number of generalized seizures, cognitive deficit, medication load, and time-length of epilepsy. Time-domain SDNN, SDNNi, SDANN, rMSDD, and pNN50 and frequency-domain LF, HF, and LF/HF parameters were analyzed. Wilcoxon and Spearman correlation tests were used. A P < .05 was considered significant. RESULTS: Patients SDNN, SDNNi, rMSSD, and pNN50 were decreased in 24-hour recordings. Although a tendency for a protective effect of sleep was seen for both patients and controls, intragroup comparisons of sleeping/waking states revealed a significant increase in sleep rMSSD (P = .046) and pNN50 (P = .041) only for controls. All 24-hour time-domain parameters and LF were inversely and significantly correlated to SUDEP-7, particularly SDANN (ρ = -0.896, P = .00019), known to deteriorate with diminished physical activity and decreased in patients with more generalized seizures. Wakefulness parameters did not correlate to SUDEP-7, whereas correlations to sleep parameters were very strong, particularly with rMSSD (ρ = -0.945, P = .00012). Cognitive deficit was associated with decreased pNN50, sleep pNN50, and LH. CONCLUSION: HRV is impaired in patients with FLE. Low HRV scores are associated with increased risk for SUDEP as measured by the SUDEP-7 score.

Effects on the Post-translational Modification of H3K4Me3, H3K9ac, H3K9Me2, H3K27Me3, and H3K36Me2 Levels in Cerebral Cortex, Hypothalamus and Pons of Rats after a Systemic Administration of Cannabidiol: A Preliminary Study.

BACKGROUND: Cannabidiol (CBD), a non-psychotropic constituent of Cannabis sativa, has shown therapeutic promises by modulating several pathological conditions, including pain, epilepsy autism, among others. However, the molecular mechanism of action of CBD remains unknown and recent data suggest the engagement on CBD´s effects of nuclear elements, such as histone activity. AIM: This study assessed the changes in the post-translational modification (PTM) on the histones H3K4Me3, H3K9ac, H3K9Me2, H3K27Me3, and H3K36Me2 in several brain regions of rats after the administration of CBD (20 mg/Kg/i.p.). OBJECTIVE: To evaluate the effects on the PTM of histones H3K4Me3, H3K9ac, H3K9Me2, H3K27Me3, and H3K36Me2 levels in the cerebral cortex, hypothalamus and pons of CBD-treated rats. METHODS: Ten adult rats were randomly assigned into 2 groups: Control or CBD (20 mg/Kg/i.p). Animals were sacrificed after treatments and brains were collected for dissections of the cerebral cortex, hypothalamus and pons. Samples were analyzed for PTM on the histones H3K4Me3, H3K9ac, H3K9Me2, H3K27Me3, and H3K36Me2 levels by Western blot procedure. RESULTS: CBD increased the PTM levels on the histones H3K4Me3, H3K9ac, and H3K27Me3 in the cerebral cortex whereas no significant differences were found in H3K9Me2 and H3K36Me2. In addition, in the hypothalamus, CBD decreased the contents of H3K9ac while no significant effects were observed in H3K4Me3, H3K9Me2, H3K27Me3, and H3K36Me2. Lastly, in the pons, CBD- treated rats showed a significant decline on the PTM levels of H3K4Me3 whereas no statistical differences were found in H3K9ac, H3K9Me2, H3K27Me3, and H3K36Me2. CONCLUSION: The study showed that CBD induced differential effects in levels of PTM on the histones H3K4Me3, H3K9ac, H3K9Me2, H3K27Me3, and H3K36Me2 in several brain regions.

Self-reported awake bruxism and chronotype profile: a multicenter study on Brazilian, Portuguese and Italian dental students.

Objective: To assess the association between self-reported awake bruxism (AB) and the chronotype profile among Brazilian, Portuguese, and Italian dental students.Methods: A cross-sectional study involving 205 dental students was developed. Self-reported AB as well as information on sleep characteristics were collected from a questionnaire. The Morningness-Eveningness Questionnaire (MEQ) was used to measure the chronotype profile. Descriptive statistical analysis, the chi-square test, and univariate analysis were used to evaluate the factors associated with AB.Results: The prevalence of AB in all groups was 33.7%. The intermediate chronotype profile was the most prevalent (60.4%), and only 16.7% of the participants had the morning profile. The univariate analysis showed that older dental students (OR = 2.640, 95% CI 1.388-5.021) and those with the eveningness chronotype profile (OR = 3.370, 95% CI 1.302-8.725) are associated with AB.Discussion: Students over the age of 22 and those with the eveningness chronotype profile were prone to AB.

Jahi McMath, a New Disorder of Consciousness / Jahi McMath, un nuevo trastorno de la conciencia / Jahi McMath, um novo transtorno da consciencia

Abstract: In this paper, I review the case of Jahi McMath, who was diagnosed with brain death (BD). Nonetheless, ancillary tests performed nine months after the initial brain insult showed conservation of intracranial structures, EEG activity, and autonomic reactivity to the "Mother Talks" stimulus. She was clinically in an unarousable and unresponsive state, without evidence of self-awareness or awareness of the environment. However, the total absence of brainstem reflexes and partial responsiveness rejected the possibility of a coma. Jahi did not have UWS because she was not in a wakefulness state and showed partial responsiveness. She could not be classified as a LIS patient either because LIS patients are wakeful and aware, and although quadriplegic, they fully or partially preserve brainstem reflexes, vertical eye movements or blinking, and respire on their own. She was not in an MCS because she did not preserve arousal and preserved awareness only partially. The CRS-R resulted in a very low score, incompatible with MCS patients. MCS patients fully or partially preserve brainstem reflexes and usually breathe on their own. MCS has always been described as a transitional state between a coma and UWS but never reported in a patient with all clinical BD findings. This case does not contradict the concept of BD but brings again the need to use ancillary tests in BD up for discussion. I concluded that Jahi represented a new disorder of consciousness, non-previously described, which I have termed "reponsive unawakefulness syndrome" (RUS).

Resumen: En este artículo, revisó el caso de Jahi McMath, quién fue diagnosticada con muerte encefálica (ME). No obstante, exámenes complementarios realizados nueve meses después de la lesión cerebral inicial mostraron conservación de las estructuras intracraneales, actividad en electroencefalografía EEG, y reactividad autonómica a estímulos llamados "Conversación de Madre". Ella estaba clínicamente en un estado sin respuesta a los estímulos, sin evidencia de autoconciencia o conciencia del ambiente. Sin embargo, la ausencia total de reflejos del tronco encefálico y la capacidad de respuesta parcial rechazaron la posibilidad de un coma. Jahi no tenía síndrome de vigilia sin respuesta SVSR porque no estaba en un estado de vigilia y mostró una capacidad de respuesta parcial. Tampoco pudo ser clasificada como paciente LIS porque los pacientes LIS están despiertos y conscientes, y aunque tetrapléjicos, conservan total o parcialmente los reflejos del tronco encefálico, los movimientos oculares verticales u el parpadeo, y respiran por sí mismos. Ella no estaba en un EMC porque no preservaba la excitación y preservaba la conciencia solo parcialmente. La CRS-R dio una puntuación muy baja, incompatible con pacientes de EMC. Los pacientes de EMC preservan total o parcialmente los reflejos del tronco encefálico y, por lo general, respirar por sí solos. El EMC siempre se ha descrito como un estado de transición entre un coma y SVSR pero nunca se ha reportado en paciente con todos los hallazgos clínicos de ME. Este caso no contradice el concepto de ME pero vuelve a plantear la discusión acerca de la necesidad de utilizar exámenes complementarios en ME. Llegué a la conclusión de que Jahi representaba un nuevo trastorno de la conciencia, no descrito anteriormente, que he denominado "síndrome de no despertar con respuesta" (SNDR).

Resumo: Neste artigo, foi revisado o caso Jahi McMath, que foi diagnosticada com morte encefálica (ME). Contudo, exames complementares realizados nove meses depois da lesão cerebral inicial mostraram conservação das estruturas intracranianas, atividade em eletroencefalografia (EEG) e reatividade autonômica a estímulos chamados "Conversación de Madre". Ela estava clinicamente em um estado sem resposta aos estímulos, sem evidência de autoconsciência ou consciência do ambiente. Contudo, a ausência total de reflexos do tronco encefálico e a capacidade de resposta parcial rejeitaram a possibilidade de um coma. Jahi não tinha síndrome de vigia sem resposta (SVSR), porque não estava em um estado de vigia e mostrou uma capacidade de resposta parcial. Também nao pode ser classificada como paciente LIS, porque estes estão acordados e conscientes, e ainda que tetraplégicos, conservam total ou parcialmente os reflexos do tronco encefálicos, os movimentos oculares verticais ou cintilação, e respiram por si próprios. Ela não estava em um EMC porque não preservava a excitação e preservava a consciencia somente parcialmente. A CRS-R deu uma pontuação muito baixa, incompatível com pacientes de EMC. Os pacientes de EMC preservam total ou parcialmente os reflexos do tronco encefálico e, em geral, respirar por si só. O EMC sempre foi descrito como um estado de transição entre coma e SVSR, mas nunca foi relatado em paciente com todos os achados clínicos de ME. Esse caso não contradiz o conceito de ME, mas volta a colocar a discussão sobre a necessidade de utilizar exames complementares em ME. Cheguei a conclusão de que Jahi representava um novo transtorno da consciencia, nao descrito anteriormente, que denominei "síndrome de resposta sem vigília" (SRSV)

Dopamine Signaling in Wake-Promoting Clock Neurons Is Not Required for the Normal Regulation of Sleep in Drosophila.

Dopamine is a wake-promoting neuromodulator in mammals and fruit flies. In Drosophila melanogaster, the network of clock neurons that drives sleep/activity cycles comprises both wake-promoting and sleep-promoting cell types. The large ventrolateral neurons (l-LNvs) and small ventrolateral neurons (s-LNvs) have been identified as wake-promoting neurons within the clock neuron network. The l-LNvs are innervated by dopaminergic neurons, and earlier work proposed that dopamine signaling raises cAMP levels in the l-LNvs and thus induces excitatory electrical activity (action potential firing), which results in wakefulness and inhibits sleep. Here, we test this hypothesis by combining cAMP imaging and patch-clamp recordings in isolated brains. We find that dopamine application indeed increases cAMP levels and depolarizes the l-LNvs, but, surprisingly, it does not result in increased firing rates. Downregulation of the excitatory D1-like dopamine receptor (Dop1R1) in the l-LNvs and s-LNvs, but not of Dop1R2, abolished the depolarization of l-LNvs in response to dopamine. This indicates that dopamine signals via Dop1R1 to the l-LNvs. Downregulation of Dop1R1 or Dop1R2 in the l-LNvs and s-LNvs does not affect sleep in males. Unexpectedly, we find a moderate decrease of daytime sleep with downregulation of Dop1R1 and of nighttime sleep with downregulation of Dop1R2. Since the l-LNvs do not use Dop1R2 receptors and the s-LNvs also respond to dopamine, we conclude that the s-LNvs are responsible for the observed decrease in nighttime sleep. In summary, dopamine signaling in the wake-promoting LNvs is not required for daytime arousal, but likely promotes nighttime sleep via the s-LNvs.SIGNIFICANCE STATEMENT In insect and mammalian brains, sleep-promoting networks are intimately linked to the circadian clock, and the mechanisms underlying sleep and circadian timekeeping are evolutionarily ancient and highly conserved. Here we show that dopamine, one important sleep modulator in flies and mammals, plays surprisingly complex roles in the regulation of sleep by clock-containing neurons. Dopamine inhibits neurons in a central brain sleep center to promote sleep and excites wake-promoting circadian clock neurons. It is therefore predicted to promote wakefulness through both of these networks. Nevertheless, our results reveal that dopamine acting on wake-promoting clock neurons promotes sleep, revealing a previously unappreciated complexity in the dopaminergic control of sleep.

Sleep and timing of death by suicide among U.S. Veterans 2006-2015: analysis of the American Time Use Survey and the National Violent Death Reporting System.

STUDY OBJECTIVES: Suicide is a top public health priority, and U.S. Veterans are recognized to be at particularly elevated risk. Sleep disturbances are an independent risk factor for suicide; recent empirical data suggest that nocturnal wakefulness may be a key mechanism underlying this association. Given higher rates of sleep disturbances among U.S. Veterans compared with civilians, we examined associations between nocturnal wakefulness and timing of death by suicide in U.S. Veterans and civilians to determine whether temporal suicide patterns differed. METHODS: The American Time Use Survey and the National Violent Death Reporting System were analyzed (2006-2015) to determine whether sleep and temporal suicide patterns differed between age-stratified groups (18-39, 40-64, and ≥65) of U.S. Veterans and civilians. Observed temporal suicide patterns were reported and standardized incidence ratios (SIRs) calculated to compare the percentage of suicides observed with those expected, given the proportion of the population awake, across clock hours. RESULTS: The raw proportion of Veteran suicides peaks between the hours of 1000-1200; however, the peak prevalence of suicide after accounting for the population awake is between 0000 and 0300 hr (p < .00001, ϕ = .88). The highest SIR was at midnight; U.S. Veterans were eight times more likely to die by suicide than expected given the population awake (SIR = 8.17; 95% CI = 7.45-8.94). CONCLUSIONS: Nocturnal wakefulness is associated with increased risk for suicide in U.S. Veterans. Overall patterns of observed suicides by clock hour were similar between U.S. Veterans and civilians. However, Veteran-specific SIRs suggest differences in magnitude of risk by clock hour across age groups. Future research examining female and Post-9/11 U.S. Veterans is warranted.

Trait-like vulnerability of higher-order cognition and ability to maintain wakefulness during combined sleep restriction and circadian misalignment.

STUDY OBJECTIVES: Determine stability of individual differences in executive function, cognitive processing speed, selective visual attention, and maintenance of wakefulness during simulated sustained operations with combined sleep restriction and circadian misalignment. METHODS: Twenty healthy adults (eight female), aged 25.7 (±4.2 SD), body mass index (BMI) 22.3 (±2.1) kg/m2 completed an 18-day protocol twice. Participants maintained habitual self-selected 8-hour sleep schedules for 2 weeks at home prior to a 4-day laboratory visit that included one sleep opportunity per day: 8 hours on night 1, 3 hours on night 2, and 3 hours on mornings 3 and 4. After 3 days of unscheduled sleep at home, participants repeated the entire protocol. Stability and task dependency of individual differences in performance were quantified by intra-class correlation coefficients (ICC) and Kendall's Tau, respectively. RESULTS: Performance on Stroop, Visual Search, and the Maintenance of Wakefulness Test were highly consistent within individuals during combined sleep restriction and circadian misalignment. Individual differences were trait-like as indicated by ICCs (0.54-0.96) classified according to standard criteria as moderate to almost perfect. Individual differences on other performance tasks commonly reported in sleep studies showed fair to almost perfect ICCs (0.22-0.94). Kendall's rank correlations showed that individual vulnerability to sleep restriction and circadian misalignment varied by task and by metric within a task. CONCLUSIONS: Consistent vulnerability of higher-order cognition and maintenance of wakefulness to combined sleep restriction and circadian misalignment has implications for the development of precision countermeasure strategies for workers performing safety-critical tasks, e.g. military, police, health care workers and emergency responders.

Sleep and Neurochemical Modulation by DZNep and GSK-J1: Potential Link With Histone Methylation Status.

Histone methylation/demethylation plays an important modulatory role in chromatin restructuring, RNA transcription and is essential for controlling a plethora of biological processes. Due to many human diseases have been related to histone methylation/demethylation, several compounds such as 3-deazaneplanocin A (DZNep) or 3-((6-(4,5-Dihydro-1H-benzo[d]azepin-3(2H)-yl)-2-(pyridin-2-yl)pyrimidin-4-yl)amino)propanoic acid; N-[2-(2-pyridinyl)-6-(1,2,4,5-tetrahydro-3H-3-benzazepin-3-yl)-4-pyrimidinyl]-ß-Alanine (GSK-J1), have been designed to inhibit histone methylase or suppress histone demethylase, respectively. In the present study, we investigated the effects on the sleep-wake cycle and sleep-related neurochemical levels after systemic injections of DZNep or GSK-J1 given during the light or dark phase in rats. DZNep dose-dependently (0.1, 1.0, or 10 mg/kg, i.p.) prolonged wakefulness (W) duration while decreased slow wave sleep (SWS) and rapid eye movement sleep (REMS) time spent during the lights-on period with no changes observed in dark phase. In opposite direction, GSK-J1 (0.1, 1.0, or 10 mg/kg, i.p.) injected at the beginning of the lights-on period induced no statistical changes in W, SWS, or REMS whereas if administered at darkness, we found a diminution in W and an enhancement in SWS and REMS. Finally, brain microdialysis experiments in freely moving animals were used to evaluate the effects of DZNep or GSK-J1 treatments on contents of sleep-related neurochemicals. The results showed that DZNep boosted extracellular levels of dopamine, norepinephrine, epinephrine, serotonin, adenosine, and acetylcholine if injected at the beginning of the lights-on period whereas GSK-J1 exerted similar outcomes but when administered at darkness. In summary, DZNep and GSK-J1 may control the sleep-wake cycle and sleep-related neurochemicals through histone methylation/demethylation activity.

Acute effect of vaporized Cannabis on sleep and electrocortical activity.

The use of Cannabis for medical purposes is rapidly expanding and is usually employed as a self-medication for the treatment of insomnia disorder. However, the effect on sleep seems to depend on multiple factors such as composition of the Cannabis, dosage and route of administration. Vaporization is the recommended route for the administration of Cannabis for medical purposes; however, there is no published research about the effects of vaporized Cannabis on sleep, neither in laboratory animals, nor in humans. Because previous reports suggested that low doses of THC have sedating effects, the aim of the present study was to characterize in rats, the acute effects on sleep induced by the administration of low doses of THC by means of vaporization of a specific type of Cannabis (THC 11.5% and negligible amounts of other cannabinoids). For this purpose, polysomnographic recordings in chronically prepared rats were performed during 6 h in the light and dark phases. Animals were treated with 0 (control), 40, 80 and 200 mg of Cannabis immediately before the beginning of recordings; the THC plasma concentrations with these doses were low (up to 6.7 ng/mL with 200 mg). A quantitative EEG analyses by means of the spectral power and coherence estimations was also performed for the highest Cannabis dose. Compared to control, 200 mg of Cannabis increased NREM sleep time during the light phase, but only during the first hour of recording. Interestingly, no changes on sleep were observed during the dark (active) phase or with lower doses of Cannabis. Cannabis 200 mg also produced EEG power reductions in different cortices, mainly for high frequency bands during W and REM sleep, but only during the light phase. On the contrary, a reduction in the sleep spindles intra-hemispheric coherence was observed during NREM sleep, but only during the dark phase. In conclusion, administration of low doses of THC by vaporization of a specific type of Cannabis produced a small increment of NREM sleep, but only during the light (resting) phase. This was accompanied by subtle modifications of high frequency bands power (during the light phase) and spindle coherence (during the dark phase), which are associated with cognitive processing. Our results reassure the importance of exploring the sleep-promoting properties of Cannabis.

A importância da mapa na doença hipertensiva / The importance of ABPM in hypertensive disease

A Monitorização Ambulatorial da Pressão Arterial (MAPA) já é uma ferramenta devidamente incorporada à prática clínica e referendada por muitas publicações principalmente pelo seu valor na detecção de situações especiais denominadas de hipertensão e efeito do avental branco; e, hipertensão mascarada e efeito mascarado da hipertensão. No Brasil, a MAPA já foi referendada por seis Diretrizes, sendo a última publicada recentemente. O objetivo desse artigo é colocar em discussão determinados aspectos que fortalecem a utilização da MAPA na prática clínica, colaborando para melhor diagnosticar e tratar os indivíduos hipertensos. Além disso, demonstrar as novas perspectivas da MAPA com a disponibilização de dispositivos capazes de avaliar a pressão periférica de 24 horas e, também, os parâmetros centrais de rigidez e hemodinâmicos que podem acrescentar muito ao tratamento da doença hipertensiva.

Ambulatory Blood Pressure Monitoring (ABPM) is already a tool duly incorporated into clinical practice and endorsed by many publications mainly for its value in the detection of special situations called hypertension and white coat effect; and, masked hypertension and masked hypertension effect. In Brazil, ABPM has already been endorsed by six Guidelines, the latter being published recently. The purpose of this article is to discuss certain aspects that strengthen the use of ABPM in clinical practice, collaborating to better diagnose and treat hypertensive individuals. In addition, to demonstrate the new perspectives of ABPM with the availability of devices capable of evaluating the 24-hour peripheral pressure and also the central parameters of stiffness and hemodynamics that can add much to the treatment of hypertensive disease.

The weaning period promotes alterations in the orexin neuronal population of rats in a suckling-dependent manner.

The orexin-immunoreactive neurons are part of an important arousal-promoting hypothalamic population. Several groups have investigated these neurons during the lactation period, when numerous physiological alterations occur in the dam's body to cope with the newly acquired metabolic needs of the litter. Although those studies have probed this population during the early and intermediate stages of lactation, few works have examined its response to weaning, including the cessation of the tactile suckling stimulus as the litter stops nursing. Using double immunohistochemistry for orexin and FOS combined with three-dimensional reconstruction techniques, we investigated orexin-synthesizing neurons and their activation at different times during weaning, in addition to the role played by the suckling stimulus. We report here that weaning promoted a decline in the anterior population of orexin-immunoreactive neurons and decreased the number of double orexin-FOS neurons labeled in the central dorsomedial hypothalamus, in addition to reducing the overall number of FOS-immunoreactive cells in the whole tuberal hypothalamus. Disruption of the suckling stimulus from the pups impaired the decrease in the number of anteriorly located orexin-immunoreactive neurons, attenuated the activation of orexin-synthesizing cells in the dorsomedial hypothalamus and reduced the number of FOS-immunoreactive neurons across the tuberal hypothalamus. When taken together, our data suggest that the weaning period is necessary to restore neurochemical pathways altered during the lactation period and that the suckling stimulus plays a significant role in this process.

Systemic Injections of Cannabidiol Enhance Acetylcholine Levels from Basal Forebrain in Rats.

Cannabis sativa is a plant that contains more than 500 components, of which the most studied are Δ9-tetrahydrocannabinol (Δ9-THC) and cannabidiol (CBD). Several studies have indicated that CBD displays neurobiological effects, including wake promotion. Moreover, experimental evidence has shown that injections of CBD enhance wake-related compounds, such as monoamines (dopamine, serotonin, epinephrine, and norepinephrine). However, no clear evidence is available regarding the effects of CBD on additional wake-related neurochemicals such as acetylcholine (ACh). Here, we demonstrate that systemic injections of CBD (0, 5, 10 or 30 mg/kg, i.p.) at the beginning of the lights-on period, increase the extracellular levels of ACh collected from the basal forebrain and measured by microdialysis and HPLC means. Moreover, the time course effects on the contents of ACh were present 5 h post-injection of CBD. Altogether, these data demonstrate that CBD increases ACh levels in a brain region related to wake control. This study is the first to show the effects of ACh levels in CBD-treated rats and suggests that the basal forebrain might be a site of action of CBD for wakefulness modulation.

Ibogaine Acute Administration in Rats Promotes Wakefulness, Long-Lasting REM Sleep Suppression, and a Distinctive Motor Profile.

Ibogaine is a potent psychedelic alkaloid that has been the focus of intense research because of its intriguing anti-addictive properties. According to anecdotic reports, ibogaine has been originally classified as an oneirogenic psychedelic; i.e., induces a dream-like cognitive activity while awake. However, the effects of ibogaine administration on wakefulness (W) and sleep have not been thoroughly assessed. The main aim of our study was to characterize the acute effects of ibogaine administration on W and sleep. For this purpose, polysomnographic recordings on chronically prepared rats were performed in the light phase during 6 h. Animals were treated with ibogaine (20 and 40 mg/kg) or vehicle, immediately before the beginning of the recordings. Furthermore, in order to evaluate associated motor behaviors during the W period, a different group of animals was tested for 2 h after ibogaine treatment on an open field with video-tracking software. Compared to control, animals treated with ibogaine showed an increase in time spent in W. This effect was accompanied by a decrease in slow wave sleep (SWS) and rapid-eye movements (REM) sleep time. REM sleep latency was significantly increased in animals treated with the higher ibogaine dose. While the effects on W and SWS were observed during the first 2 h of recordings, the decrement in REM sleep time was observed throughout the recording time. Accordingly, ibogaine treatment with the lower dose promoted an increase on locomotion, while tremor and flat body posture were observed only with the higher dose in a time-dependent manner. In contrast, head shake response, a behavior which has been associated in rats with the 5HT2A receptor activation by hallucinogens, was not modified. We conclude that ibogaine promotes a waking state that is accompanied by a robust and long-lasting REM sleep suppression. In addition, it produces a dose-dependent unusual motor profile along with other serotonin-related behaviors. Since ibogaine is metabolized to produce noribogaine, further experiments are needed to elucidate if the metabolite and/or the parent drug produced these effects.

Zolpidem efficacy and safety in disorders of consciousness.

Sutton and Clauss presented a detailed review about the effectiveness of zolpidem, discussing recoveries from brain damage due to strokes, trauma and hypoxia. A significant finding has been the unexpected and paradoxical increment of brain activity in vegetative state/unresponsive wakefulness syndrome (VS/UWS). On the contrary, zolpidem is considered one of the best sleep inducers in normal subjects. We have studied series of VS/UWS cases after zolpidem intake. We have demonstrated EEG activation, increment of BOLD signal in different brain regions, and an autonomic influence, mainly characterized by a vagolytic chronotropic effect without a significant increment of the vasomotor sympathetic tone. As this autonomic imbalance might induce cardio- circulatory complications, which we didn't find in any of our patients, we suggest developing future trials under control of physiological indices by bedside monitoring. However, considering that the paradoxical arousing zolpidem effect might be certainly related to brain function improvement, we agree with Sutton and Clauss that future multicentre and multinational clinical trials should be developed, but under control of physiological indices.

Detection of electroencephalographic, electromyographic, and cardiac variations during wake-sleep transition through change point analysis / Detección de variaciones electroencefalográficas, electromiográficas y cardiacas durante la transición vigilia-sueño por medio del análisis de punto de cambio

Abstract: Introduction: Wake-sleep transition is a continuous, gradual process of change. Most studies evaluating electroencephalogram spectral power during this transition have used variance analysis (ANOVA). However, using this type of analysis does not allow one to detect specific changes in the statistical properties of a time series. Objective: To determine whether change point analysis (CPA) makes it possible to identify and characterize electroencephalographic, electromyographic, and cardiac changes during the wake-sleep transition through a cross-sectional study. Method: The study included 18 healthy volunteers (12 women and six men), from which polysomnography data were obtained during a two-minute transition. Heart rate, respiratory sinus arrhythmia, electroencephalogram spectral power, as well as electromyographic median and mean frequency and electromyographic root mean square were calculated in five-second segments. These segments were analyzed using repeated measures ANOVA, and CPA focused individually and for the group as a whole. Results: Repeated measures ANOVA and CPA by group found decreased levels of alpha and beta power and beta/delta index during wakefulness, and increased theta and delta power levels during sleep. CPA by individual found that only alpha power changed in all participants and failed to identify a specific moment when all the variables studied changed simultaneously. Discussion and conclusion: We consider that CPA provides additional information to statistical analyses such as ANOVA for the specific location of physiological changes during sleep-wake transition.

Resumen: Introducción: La transición vigilia-sueño es un proceso de cambio continuo y gradual. Los estudios que han evaluado el poder espectral del electroencefalograma (EEG) durante esta transición han usado principalmente el análisis de varianza (ANOVA). Sin embargo, con este tipo de análisis no se pueden ubicar con precisión los cambios en las propiedades estadísticas de series de tiempo. Objetivo: Evaluar si el análisis de punto de cambio (APC) permite identificar y caracterizar cambios electroencefalográficos, electromiográficos y cardiacos durante la transición vigilia-sueño mediante un estudio transversal descriptivo. Método: Participaron 18 voluntarios sanos (12 mujeres y seis hombres) a los cuales se les realizó una polisomnografía para determinar un periodo de transición de dos minutos. En segmentos de cinco segundos se calcularon la frecuencia cardiaca, arritmia del sinus respiratorio, frecuencia mediana y media cuadrática del electromiograma y poder espectral del EEG. Estos segmentos se analizaron con ANOVA de medidas repetidas y con el APC que se aplicó de forma grupal e individual. Resultados: Con el ANOVA de medidas repetidas y el APC grupal se encontraron disminución de la potencia alfa, beta e índice beta/delta durante la vigilia e incrementos de theta y delta durante el sueño. Con el APC individual no se identificó un momento específico en el que todas las variables estudiadas cambiaran simultáneamente; además, se encontró que sólo la potencia alfa cambió en todos los participantes. Discusión y conclusión: El APC aportó información adicional al ANOVA ya que permitió conocer la ubicación específica de los cambios en las variables fisiológicas estudiadas durante la transición vigilia-sueño.

Neuro-behavioral pattern of sleep bruxism in wakefulness

AbstractIntroduction: Sleep Bruxism (SB) is a non-functional rhythmic movement of the mandible with multifactorial aetiology and complex diagnose. It has been the subject of various studies over the past decades and it is considered a result of actions of the Central Nervous System modulated by Autonomous Nervous System. In this work, we test the hypothesis that SB subjects present a typical and defined neurobehavioral pattern that can be distinct from that of non-bruxers subjects and can be measured during wakefulness. Methods Fifteen sleep bruxers (experimental-group EG) and fifteen non-bruxers (control-group CG) took part in the experiments. To verify the presence and severity of SB, clinical examinations, anamneses and questionnaires, including Visual Analogic Scale - faces (VAS-f) and State-Trait Anxiety Inventory (STAI) were applied. To legitimate the diagnoses of SB, a disposable instrument (Bitestrip®) to assess the masseter activity during sleep was employed. All subjects were submitted to a set of experiments for measuring various visual evoked responses during the presentation of visual stimuli (pleasant, unpleasant and neutral images). Events in Visual Evoked Potential (VEP) were used to compare the neural responses of both CG and EG. Results VAS-f showed EG with higher perception of stress than CG (trait: p=0.05), and lower quality of life for (state: p=0.007). STAI I and II showed significant differences of anxiety between CG and EG (p=0.013 and p=0.004, respectively), being EG the highest. The EG Bitestrip scores confirmed that 100% of subjects were sleep bruxers. Significant differences were found between EG and CG for events associated with emotional (pleasant and unpleasant) images in the first 250 ms after stimulation. In general, EG subjects showed higher amplitude and shorter latency of VEP events. Conclusion It is possible to distinguish between SB and non-bruxers subjects during wakefulness, based on differences in amplitude and latency of cortical event related potentials elicited by visual stimulation. SB subjects show greater amplitudes in specific events in frontal areas when non-pleasant images are shown. Latencies tend to be anticipated in SB compared to CG subjects.