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1.
J Neuroinflammation ; 21(1): 94, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38622640

RESUMO

BACKGROUND: Traumatic brain injury (TBI) causes significant blood-brain barrier (BBB) breakdown, resulting in the extravasation of blood proteins into the brain. The impact of blood proteins, especially fibrinogen, on inflammation and neurodegeneration post-TBI is not fully understood, highlighting a critical gap in our comprehension of TBI pathology and its connection to innate immune activation. METHODS: We combined vascular casting with 3D imaging of solvent-cleared organs (uDISCO) to study the spatial distribution of the blood coagulation protein fibrinogen in large, intact brain volumes and assessed the temporal regulation of the fibrin(ogen) deposition by immunohistochemistry in a murine model of TBI. Fibrin(ogen) deposition and innate immune cell markers were co-localized by immunohistochemistry in mouse and human brains after TBI. We assessed the role of fibrinogen in TBI using unbiased transcriptomics, flow cytometry and immunohistochemistry for innate immune and neuronal markers in Fggγ390-396A knock-in mice, which express a mutant fibrinogen that retains normal clotting function, but lacks the γ390-396 binding motif to CD11b/CD18 integrin receptor. RESULTS: We show that cerebral fibrinogen deposits were associated with activated innate immune cells in both human and murine TBI. Genetic elimination of fibrin-CD11b interaction reduced peripheral monocyte recruitment and the activation of inflammatory and reactive oxygen species (ROS) gene pathways in microglia and macrophages after TBI. Blockade of the fibrin-CD11b interaction was also protective from oxidative stress damage and cortical loss after TBI. CONCLUSIONS: These data suggest that fibrinogen is a regulator of innate immune activation and neurodegeneration in TBI. Abrogating post-injury neuroinflammation by selective blockade of fibrin's inflammatory functions may have implications for long-term neurologic recovery following brain trauma.


Assuntos
Lesões Encefálicas Traumáticas , Fibrina , Humanos , Camundongos , Animais , Fibrina/genética , Fibrina/metabolismo , Lesões Encefálicas Traumáticas/patologia , Fibrinogênio/metabolismo , Imunidade Inata , Estresse Oxidativo , Camundongos Endogâmicos C57BL
2.
eNeuro ; 11(3)2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38233145

RESUMO

In critically ill newborns, exposure to hypercapnia (HC) is common and often accepted in neonatal intensive care units to prevent severe lung injury. However, as a "safe" range of arterial partial pressure of carbon dioxide levels in neonates has not been established, the potential impact of HC on the neurodevelopmental outcomes in these newborns remains a matter of concern. Here, in a newborn Yorkshire piglet model of either sex, we show that acute exposure to HC induced persistent cortical neuronal injury, associated cognitive and learning deficits, and long-term suppression of cortical electroencephalogram frequencies. HC induced a transient energy failure in cortical neurons, a persistent dysregulation of calcium-dependent proapoptotic signaling in the cerebral cortex, and activation of the apoptotic cascade, leading to nuclear deoxyribonucleic acid fragmentation. While neither 1 h of HC nor the rapid normalization of HC was associated with changes in cortical bioenergetics, rapid resuscitation resulted in a delayed onset of synaptosomal membrane lipid peroxidation, suggesting a dissociation between energy failure and the occurrence of synaptosomal lipid peroxidation. Even short durations of HC triggered biochemical responses at the subcellular level of the cortical neurons resulting in altered cortical activity and impaired neurobehavior. The deleterious effects of HC on the developing brain should be carefully considered as crucial elements of clinical decisions in the neonatal intensive care unit.


Assuntos
Hipercapnia , Respiração Artificial , Animais , Suínos , Hipercapnia/complicações , Animais Recém-Nascidos , Respiração Artificial/métodos , Córtex Cerebral , Cognição
3.
Glia ; 71(5): 1164-1175, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-36692058

RESUMO

Traumatic brain injury (TBI) is a significant worldwide cause of morbidity and mortality. A chronic neurologic disease bearing the moniker of "the silent epidemic," TBI currently has no targeted therapies to ameliorate cellular loss or enhance functional recovery. Compared with those of astrocytes, microglia, and peripheral immune cells, the functions and mechanisms of NG2-glia following TBI are far less understood, despite NG2-glia comprising the largest population of regenerative cells in the mature cortex. Here, we synthesize the results from multiple rodent models of TBI, with a focus on cortical NG2-glia proliferation and lineage potential, and propose future avenues for glia researchers to address this unique cell type in TBI. As the molecular mechanisms that regulate NG2-glia regenerative potential are uncovered, we posit that future therapeutic strategies may exploit cortical NG2-glia to augment local cellular recovery following TBI.


Assuntos
Lesões Encefálicas Traumáticas , Neuroglia , Humanos , Neuroglia/metabolismo , Microglia , Astrócitos , Lesões Encefálicas Traumáticas/metabolismo , Neurogênese , Antígenos/metabolismo
4.
eNeuro ; 9(5)2022.
Artigo em Inglês | MEDLINE | ID: mdl-36123116

RESUMO

The molecular circadian clock can be found throughout the body and is essential for the synchronizing cellular physiology with the 24 h day. However, the role of the clock in regulating the regenerative potential of the brain has not been explored. We report here that murine NG2-glia, the largest population of proliferative cells in the mature central nervous system, rhythmically express circadian clock genes in a 24 h period, including the critical clock component Bmal1 RNA and BMAL1 protein. Interestingly, daily NG2-glia proliferation preferentially occurs during the time of day in which Bmal1 expression is high, while conditional knockout of Bmal1 decreases both cortical NG2-glia density and cellular proliferation. Furthermore, in a neurotrauma model, we show that pathology-induced NG2-glia proliferation is also dependent on Bmal1 expression. Because circadian rhythm disturbances are common in neurologic disorders across the life span, including in traumatic brain injury, these findings bear significant implications for cellular regeneration in brain injuries and disease.


Assuntos
Fatores de Transcrição ARNTL , Relógios Circadianos , Fatores de Transcrição ARNTL/genética , Fatores de Transcrição ARNTL/metabolismo , Animais , Proliferação de Células , Ritmo Circadiano/fisiologia , Camundongos , Neuroglia/metabolismo , RNA
5.
Pediatr Pulmonol ; 57(1): 325-329, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34710278

RESUMO

As many as 6% of reported cinnamon poisonings cause significant clinical effects, however, descriptions of pulmonary toxicity have not yet been reported. Here, we present a pediatric patient's hospital course following powdered cinnamon aspiration. The early presentation with hypercapnia and lower airways obstruction evolved to hypoxemic respiratory failure and severe pediatric acute respiratory distress syndrome requiring a 7-day course of veno-venous extracorporeal membrane oxygenation, 16 ventilator-days, and three diagnostic and therapeutic bronchoscopies with two applications of surfactant therapy. The sum of these modalities contributed to this patient's survival and subsequent return to respiratory baseline 6 months post-hospitalization.


Assuntos
Oxigenação por Membrana Extracorpórea , Síndrome do Desconforto Respiratório , Insuficiência Respiratória , Criança , Pré-Escolar , Cinnamomum zeylanicum , Humanos , Síndrome do Desconforto Respiratório/etiologia , Síndrome do Desconforto Respiratório/terapia , Insuficiência Respiratória/etiologia , Insuficiência Respiratória/terapia , Tensoativos
6.
Nat Neurosci ; 24(1): 19-23, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33318667

RESUMO

Microglial surveillance is a key feature of brain physiology and disease. Here, we found that Gi-dependent microglial dynamics prevent neuronal network hyperexcitability. By generating MgPTX mice to genetically inhibit Gi in microglia, we show that sustained reduction of microglia brain surveillance and directed process motility induced spontaneous seizures and increased hypersynchrony after physiologically evoked neuronal activity in awake adult mice. Thus, Gi-dependent microglia dynamics may prevent hyperexcitability in neurological diseases.


Assuntos
Receptor Quinase 1 Acoplada a Proteína G/fisiologia , Microglia/fisiologia , Rede Nervosa/fisiologia , Animais , Sinalização do Cálcio , Movimento Celular , Convulsivantes , Eletroencefalografia , Vigilância Imunológica , Camundongos , Microglia/enzimologia , Microglia/ultraestrutura , Doenças do Sistema Nervoso/fisiopatologia , Fenômenos Fisiológicos do Sistema Nervoso , Pilocarpina , Convulsões/fisiopatologia , Transdução de Sinais , Proteínas rho de Ligação ao GTP/metabolismo
8.
Pediatr Pulmonol ; 54(10): 1602-1609, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31270964

RESUMO

INTRODUCTION: Survivors of childhood cancers undergo routine pulmonary function testing as they are at an increased lifetime risk for significant lung disease. However, this population also demonstrates growth abnormalities that could influence the interpretation of these tests, as reference equations are based on standing height. We aim to determine the impact of the relative thoracic growth deficiency in childhood cancer survivors on the interpretation of pulmonary function testing. METHODS: Standing height and upper segment length (USL) in childhood cancer survivors undergoing pulmonary function testing at a single academic center were compared to age-matched historical standards. Additionally, pulmonary function tests were compared to reference values generated from standing height and doubled USL. RESULTS: Data were obtained from 107 cancer survivors. While the subjects demonstrated an overall 6.8% lower standing height vs historical standards, they also demonstrated relative thoracic growth abnormality with a further 9.9% decrement in the ratio USL to standing height. The use of doubled upper segment length as a surrogate measure for standing height in pulmonary function reference equations decreased the number of patients with restrictive lung disease as indicated by spirometry. CONCLUSIONS: Childhood cancer survivors have disproportionately worse thoracic growth deficiency vs appendicular growth deficiency. As a result, their USL is disproportionately short for their standing height, which is most commonly used in pulmonary function testing reference equations. This leads to an increased likelihood in these patients meeting pulmonary function test criteria for restrictive lung disease.


Assuntos
Estatura , Sobreviventes de Câncer , Pneumopatias/fisiopatologia , Tórax/anatomia & histologia , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Pulmão/fisiopatologia , Masculino , Valores de Referência , Testes de Função Respiratória , Adulto Jovem
9.
J Med Libr Assoc ; 107(3): 374-383, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31258443

RESUMO

OBJECTIVE: This study updates Haaland's 1999 dental hygiene mapping study. By identifying core journals and estimating database coverage, it characterizes changes in dental hygiene research and aids librarians in collection development and user education. METHOD: Cited references from a three-year (2015-2017) sample of core dental hygiene journals were collected, categorized into five formats, and analyzed by format and publication year according to Bradford's Law of Scattering. CINAHL Complete, MEDLINE, and EMBASE were surveyed to determine the indexing coverage of cited journals. RESULTS: The number of cited journal titles increased from 389 in 1999 to 1,675 in 2018. Core Zone 1 titles increased from 5 to 11. Journal article citations increased from 69.5% of all citations in 1999 to 78.4% in the present study, whereas book citations decreased from 18.1% to 5.1%. A newly added category, "Internet sources," accounted for 8.4% of citations. Overall, 68.6% of citations were 10 years or younger versus 71.4% in 1999. Most Zone 1 and Zone 2 journals were specific to dentistry or dental hygiene. CONCLUSION: Notable changes since 1999 were an increased volume of literature and a shift from print to online sources, reflecting improved accessibility of the literature and greater Internet use. From 1999 to 2018, citations to journal articles increased, books decreased, websites appeared, and government publications increased slightly. These findings indicate that dental hygiene research is growing and that indexing coverage for this field has improved dramatically in the past two decades.


Assuntos
Bibliometria , Bases de Dados Bibliográficas/estatística & dados numéricos , Higiene Bucal , Publicações Periódicas como Assunto/estatística & dados numéricos , Humanos
10.
Pulm Circ ; 9(1): 2045894018812052, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30351242

RESUMO

We report a case of a six-year-old boy who presented after a cardiac arrest, likely due to a pulmonary hypertensive crisis in the setting of vitamin C deficiency. After initially presenting with subacute multifocal bone lesions of unknown etiology, he experienced a pulseless electrical activity cardiac arrest while undergoing a diagnostic procedure under sedation. During his post-arrest convalescence, he developed persistent tachycardia and peripheral edema. An echocardiogram revealed findings consistent with significant pulmonary arterial hypertension, which was found to be responsive to inhaled nitric oxide. Laboratory investigation revealed undetectable levels of vitamin C, resulting in disclosure of a history of severe restrictive eating behavior. With ascorbate supplementation, the patient's pulmonary vasodilators were weaned and discontinued. Given his complete recovery, we suspect that the cardiac arrest and pulmonary hypertension were the consequence of a rare, but reversible, complication of scurvy.

11.
Sleep ; 39(2): 345-56, 2016 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-26350473

RESUMO

STUDY OBJECTIVES: Sleep is under the control of homeostatic and circadian processes, which interact to determine sleep timing and duration, but the mechanisms through which the circadian system modulates sleep are largely unknown. We therefore used adult-specific, temporally controlled neuronal activation and inhibition to identify an interaction between the circadian clock and a novel population of sleep-promoting neurons in Drosophila. METHODS: Transgenic flies expressed either dTRPA1, a neuronal activator, or Shibire(ts1), an inhibitor of synaptic release, in small subsets of neurons. Sleep, as determined by activity monitoring and video tracking, was assessed before and after temperature-induced activation or inhibition using these effector molecules. We compared the effect of these manipulations in control flies and in mutant flies that lacked components of the molecular circadian clock. RESULTS: Adult-specific activation or inhibition of a population of neurons that projects to the sleep-promoting dorsal Fan-Shaped Body resulted in bidirectional control over sleep. Interestingly, the magnitude of the sleep changes were time-of-day dependent. Activation of sleep-promoting neurons was maximally effective during the middle of the day and night, and was relatively ineffective during the day-to-night and night-to-day transitions. These time-ofday specific effects were absent in flies that lacked functional circadian clocks. CONCLUSIONS: We conclude that the circadian system functions to gate sleep through active inhibition at specific times of day. These data identify a mechanism through which the circadian system prevents premature sleep onset in the late evening, when homeostatic sleep drive is high.


Assuntos
Relógios Circadianos/fisiologia , Ritmo Circadiano/fisiologia , Drosophila melanogaster/fisiologia , Neurônios/fisiologia , Sono/fisiologia , Animais , Animais Geneticamente Modificados , Relógios Circadianos/genética , Ritmo Circadiano/genética , Proteínas de Drosophila/metabolismo , Drosophila melanogaster/citologia , Drosophila melanogaster/genética , Dinaminas/metabolismo , Feminino , Homeostase , Canais Iônicos , Mutação/genética , Canal de Cátion TRPA1 , Canais de Cátion TRPC/metabolismo , Temperatura , Fatores de Tempo
13.
J Neurosci ; 31(31): 11387-95, 2011 Aug 03.
Artigo em Inglês | MEDLINE | ID: mdl-21813698

RESUMO

The quiver/sleepless (qvr/sss) gene encodes a small, glycosylphosphatidylinositol-anchored protein that plays a critical role in the regulation of sleep in Drosophila. Loss-of-function mutations in qvr/sss severely suppress sleep and effect multiple changes in in situ Shaker K(+) currents, including decreased magnitude, slower time-to-peak, and cumulative inactivation. Recently, we demonstrated that SLEEPLESS (SSS) protein modulates Shaker channel activity, possibly through a direct interaction at the plasma membrane. We show here that SSS accelerates the activation of heterologously expressed Shaker channels with no effect on deactivation or fast N-type inactivation. Furthermore, this SSS-induced acceleration is sensitive to the pharmacological disruption of lipid rafts and sufficiently accounts for the slower time-to-peak of in situ Shaker currents seen in qvr/sss mutants. We also find that SSS decreases the rate of C-type inactivation of heterologously expressed Shaker channels, providing a potential mechanism for the cumulative inactivation phenotype induced by qvr/sss loss-of-function mutations. Kinetic modeling based on the in vitro results suggests that the SSS-dependent regulation of channel kinetics accounts for nearly 40% of the decrease in Shaker current magnitude in flies lacking SSS. Sleep duration in qvr/sss-null mutants is restored to normal by a qvr/sss transgene that fully rescues the Shaker kinetic phenotypes but only partially rescues the decrease in current magnitude. Together, these results suggest that the role of SSS in the regulation of sleep in Drosophila correlates more strongly with the effects of SSS on Shaker kinetics than current magnitude.


Assuntos
Proteínas de Drosophila/metabolismo , Proteínas de Membrana/metabolismo , Superfamília Shaker de Canais de Potássio/metabolismo , Animais , Animais Geneticamente Modificados , Biofísica , Linhagem Celular Transformada , Drosophila , Proteínas de Drosophila/genética , Estimulação Elétrica/métodos , Humanos , Técnicas In Vitro , Ativação do Canal Iônico/genética , Cinética , Microdomínios da Membrana/metabolismo , Potenciais da Membrana/genética , Proteínas de Membrana/genética , Músculos/fisiologia , Mutação/genética , Técnicas de Patch-Clamp , Superfamília Shaker de Canais de Potássio/genética , Distúrbios do Início e da Manutenção do Sono/genética , Distúrbios do Início e da Manutenção do Sono/metabolismo , Transfecção
14.
Nat Neurosci ; 13(1): 69-75, 2010 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-20010822

RESUMO

Sleep is a whole-organism phenomenon accompanied by global changes in neural activity. We previously identified SLEEPLESS (SSS) as a glycosylphosphatidyl inositol-anchored protein required for sleep in Drosophila. Here we found that SSS is critical for regulating the sleep-modulating potassium channel Shaker. SSS and Shaker shared similar expression patterns in the brain and specifically affected each other's expression levels. sleepless (sss) loss-of-function mutants exhibited altered Shaker localization, reduced Shaker current density and slower Shaker current kinetics. Transgenic expression of sss in sss mutants rescued defects in Shaker expression and activity cell-autonomously and suggested that SSS functions in wake-promoting, cholinergic neurons. In heterologous cells, SSS accelerated the kinetics of Shaker currents and was co-immunoprecipitated with Shaker, suggesting that SSS modulates Shaker activity via a direct interaction. SSS is predicted to belong to the Ly-6/neurotoxin superfamily, suggesting a mechanism for regulation of neuronal excitability by endogenous toxin-like molecules.


Assuntos
Proteínas de Drosophila/metabolismo , Proteínas de Drosophila/fisiologia , Regulação da Expressão Gênica/genética , Proteínas de Membrana/fisiologia , Superfamília Shaker de Canais de Potássio/metabolismo , Animais , Animais Geneticamente Modificados , Comportamento Animal/fisiologia , Encéfalo/citologia , Encéfalo/metabolismo , Linhagem Celular Transformada , Drosophila , Proteínas de Drosophila/genética , Feminino , Proteínas de Fluorescência Verde/genética , Humanos , Imunoprecipitação/métodos , Técnicas In Vitro , Larva , Mutação/genética , Junção Neuromuscular/genética , Junção Neuromuscular/fisiologia , Células Receptoras Sensoriais/metabolismo , Sono/genética , Vigília/genética
15.
Cell ; 139(2): 225-7, 2009 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-19837025

RESUMO

Examining different aspects of learning and memory, Claridge-Chang et al. (2009) and Krashes et al. (2009) converge on the same set of neurons in the protocerebral posterior lateral 1 (PPL1) cluster in Drosophila melanogaster. The different roles attributed to PPL1 neurons demonstrate heterogeneity of function in small neuronal subsets of the Drosophila brain.


Assuntos
Drosophila melanogaster/fisiologia , Neurônios/fisiologia , Animais , Encéfalo/fisiologia , Aprendizagem , Memória , Vias Neurais
16.
Sleep Med ; 7(8): 634-40, 2006 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-17098470

RESUMO

OBJECTIVES: Iron deficiency is considered a putative cause for restless legs syndrome (RLS), a human sensorimotor disorder characterized by a circadian presentation of symptoms during the evening hours that disrupts one's ability to sleep. We sought to evaluate the sleep-wake effects of diet-induced iron deficiency in mice as an animal model of RLS. To this end, we hypothesized that the iron-deprived mice would exhibit a sleep-wake circadian pattern characteristic of the human syndrome: increased wakefulness during the hours immediately preceding the sleep-predominant period. METHODS: Following weaning at post-natal day (PND) 21, C57BL/6J mice were assigned to one of two dietary treatments: iron-deficient (ID, n=7) or iron-adequate (i.e., control, CTL, n=6). At PND 44, the mice were surgically instrumented for polysomnographic (PSG) recording, and data were collected at young adulthood: PNDs 59 and 60. Sleep-wake architecture was characterized for the 12-h light and dark periods and also for six consecutive 4-h blocks comprising a 24-h day. RESULTS: The ID mice showed marked increases in wake time in the 4-h period prior to lights-on; both non-rapid eye movement (NREM) and rapid eye movement (REM) sleep were reduced. In contrast, sleep-wake activity did not differ across the 12-h light period. CONCLUSIONS: Dietary iron deficiency in mice elicited increases in wakefulness during a particular circadian time point that corresponds to the period during which RLS symptoms would maximally disturb sleep onset and progression in humans. These data indicate that iron-deficient mice may provide a potentially useful animal model for RLS.


Assuntos
Deficiências de Ferro , Síndrome das Pernas Inquietas/etiologia , Animais , Ritmo Circadiano/fisiologia , Deficiências Nutricionais/complicações , Deficiências Nutricionais/fisiopatologia , Modelos Animais de Doenças , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Polissonografia , Síndrome das Pernas Inquietas/fisiopatologia , Sono/fisiologia
17.
Sleep Med ; 7(1): 25-30, 2006 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-16198145

RESUMO

BACKGROUND AND PURPOSE: Restless legs syndrome produces significant chronic sleep loss, which despite not causing expected profound sleepiness, might nonetheless produce cognitive deficits similar to those seen with acute sleep deprivation, i.e. involving mostly pre-frontal cortical (PFC) functioning. PATIENTS AND METHODS: Sixteen patients off RLS treatment for at least 2 weeks and 15 age- and gender-matched control subjects had polysomnograms (PSGs) on two consecutive nights. Cognitive tests were given in the morning after the second night. Six cognitive tests were used: two Verbal Fluency tests and the Trail Making tests were selected to be particularly sensitive to PFC function and sleep loss. Porteus Mazes and the Stroop Test were selected to reflect more general frontal and executive function. The Colored Progressive Matrices were used to assess general cognitive skills. RESULTS: RLS patients compared to controls showed significant (P<0.05) and sizeable (20-40%) deficits on two of the three PFC tests and marginally non-significant deficit (P<0.1) on the third. The other three tests showed no significant differences. CONCLUSIONS: The results indicate that RLS patients show cognitive deficits similar to that reported for one night of sleep loss.


Assuntos
Transtornos Cognitivos/epidemiologia , Síndrome das Pernas Inquietas/epidemiologia , Idoso , Doença Crônica , Transtornos Cognitivos/diagnóstico , Eletrocardiografia , Eletroencefalografia , Eletromiografia , Eletroculografia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos , Polissonografia , Córtex Pré-Frontal/fisiopatologia , Síndrome das Pernas Inquietas/diagnóstico , Síndrome das Pernas Inquietas/fisiopatologia , Índice de Gravidade de Doença , Privação do Sono/diagnóstico , Privação do Sono/epidemiologia , Teste de Sequência Alfanumérica , Comportamento Verbal
18.
Sleep Med ; 7(1): 7-16, 2006 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-16309961

RESUMO

BACKGROUND AND PURPOSE: Obstructive sleep apnea (OSA) severely impairs sleep architecture. We hypothesized that both intermittent hypoxia (IH) and non-hypoxic arousals of OSA result in significant disruption of non-rapid eye movement sleep (NREMS) and rapid eye movement sleep (REMS). PATIENTS AND METHODS: Polysomnography was performed in C57BL/6J mice (n=5) exposed to IH (cycling of FIO2 from 20.9 to 5.0%) or sleep fragmentation (SF: high flow air blasts) throughout the 12-h light phase over 5 consecutive days. RESULTS: Both IH and SF induced arousals from sleep. On Day 1 of exposure, total NREMS during the light phase decreased comparably during IH (44.1+/-7.8%/12h, P<0.05) and SF (43.7+/-3.3%/12h, P<0.05) but returned to baseline levels of 62.0+/-7.8%/12h by Day 5 of exposure under both conditions. During IH, however, the electroencephalographic (EEG) delta power of NREMS remained impaired throughout the 5-day period of IH with a nadir of 65.4+/-5.6% relative to baseline (P=0.01), and REMS was effectively abolished during the light phase. In contrast, SF did not cause a significant reduction in either EEG delta power or REMS during the light phase. CONCLUSIONS: Thus, hypoxic exposure, but not arousals, caused overall deficits in the EEG delta power of NREMS and marked deficits in the total amount of REMS. We propose that hypoxic arousals may have a more severe impact on sleep architecture in patients with OSA than non-hypoxic arousals.


Assuntos
Ritmo Delta , Eletroencefalografia , Hipóxia/fisiopatologia , Apneia Obstrutiva do Sono/complicações , Apneia Obstrutiva do Sono/fisiopatologia , Sono REM/fisiologia , Animais , Modelos Animais de Doenças , Hipóxia/etiologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Polissonografia , Índice de Gravidade de Doença , Síndromes da Apneia do Sono/etiologia , Privação do Sono/epidemiologia , Privação do Sono/etiologia , Fases do Sono/fisiologia
19.
Sleep Med ; 6(5): 429-34, 2005 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-16099215

RESUMO

BACKGROUND AND PURPOSE: The diagnostic criteria for restless legs syndrome (RLS) indicate that both time-of-day and rest effects induce or aggravate symptoms. Periodic limb movements while awake (PLMW) provide an objective motor sign of RLS that can be measured during an awake suggested immobilization test (SIT). This study uses the SIT at different times of the day and analyzes time-of-day and duration-of-rest effects and their interaction on the PLMW. PATIENTS AND METHODS: Twenty-eight RLS patients who were not on medications had SIT tests at 10 pm, 8 am and 4 pm on two consecutive days. PLMW for each 20-min period were analyzed for time-of-day and rest effects and their interaction. PLMW increase from the first to last 20-min SIT period assessed the rest-effects. RESULTS: Significant effects were found for rest, time-of-day and rest-time-of-day interaction. The rest-effect increased most from morning to afternoon while total PLMW increased more from afternoon to night. Males compared to females had significantly more PLMW and a larger rest-effect change with time-of-day. CONCLUSIONS: Rest and time-of-day effects and their interaction all increase RLS symptoms. PLMW increase with rest may provide a sensitive measure of symptom severity.


Assuntos
Síndrome da Mioclonia Noturna/fisiopatologia , Descanso/fisiologia , Síndrome das Pernas Inquietas/fisiopatologia , Vigília/fisiologia , Fatores Etários , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Síndrome da Mioclonia Noturna/complicações , Polissonografia , Síndrome das Pernas Inquietas/complicações , Restrição Física , Fatores Sexuais , Fatores de Tempo
20.
Mov Disord ; 20(9): 1097-103, 2005 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-15895424

RESUMO

We evaluated rest effects on restless legs syndrome (RLS) sensory and motor symptoms. During two 60-minute Suggested Immobilization Tests (SIT) subject's signals of RLS leg sensations and periodic leg movements while awake (PLMW) were recorded. Sensations, PLMW, sensations preceding or after PLMW, sensations occurring without following PLMW, and PLMW occurring without preceding sensation were determined. The RLS patients were divided into equal-sized high and low PLMW groups for further analysis. Data from 46 subjects (28 RLS and 18 controls) revealed sensations increased linearly with rest in RLS patients and controls. Movement rate increased linearly with rest for controls but increased rapidly for the first 45 minutes for all RLS patients. PLMW/hour increased with further rest for low but not high PLMW patients. Sensations followed by PLMW and PLMW without preceding sensations followed similar patterns. Sensations without subsequent PLMW increased dramatically in the last 15 minutes of the SITs. Whereas both sensory and motor signs of RLS increase with rest, there is minimal increase for controls. Patients with higher but not lower PLMW rates reached a ceiling for PLMW after 35 to 40 minutes. The temporal dissociation between sensory and motor events supports viewing these motor and sensory events as separate but loosely linked manifestations of RLS.


Assuntos
Perna (Membro)/fisiologia , Movimento/fisiologia , Síndrome das Pernas Inquietas/epidemiologia , Síndrome das Pernas Inquietas/fisiopatologia , Sensação , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Descanso , Síndrome das Pernas Inquietas/diagnóstico , Índice de Gravidade de Doença
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