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1.
Proc Natl Acad Sci U S A ; 117(38): 23925-23931, 2020 09 22.
Artigo em Inglês | MEDLINE | ID: mdl-32900929

RESUMO

Medin is the most common amyloid known in humans, as it can be found in blood vessels of the upper body in virtually everybody over 50 years of age. However, it remains unknown whether deposition of Medin plays a causal role in age-related vascular dysfunction. We now report that aggregates of Medin also develop in the aorta and brain vasculature of wild-type mice in an age-dependent manner. Strikingly, genetic deficiency of the Medin precursor protein, MFG-E8, eliminates not only vascular aggregates but also prevents age-associated decline of cerebrovascular function in mice. Given the prevalence of Medin aggregates in the general population and its role in vascular dysfunction with aging, targeting Medin may become a novel approach to sustain healthy aging.


Assuntos
Envelhecimento/metabolismo , Amiloide/metabolismo , Antígenos de Superfície/metabolismo , Proteínas do Leite/metabolismo , Doenças Vasculares/metabolismo , Idoso de 80 Anos ou mais , Amiloide/genética , Animais , Antígenos de Superfície/genética , Aorta/metabolismo , Aorta/patologia , Química Encefálica/fisiologia , Circulação Cerebrovascular/fisiologia , Feminino , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Proteínas do Leite/genética , Doenças Vasculares/patologia
2.
PLoS One ; 15(8): e0236986, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32866198

RESUMO

White matter hyperintensities (WMHs) are among the most commonly observed marker of cerebrovascular disease. Age is a key risk factor for WMH development. Cardiorespiratory fitness (CRF) is associated with increased vessel compliance, but it remains unknown if high CRF affects WMH volume. This study explored the effects of CRF on WMH volume in community-dwelling older adults. We further tested the possibility of an interaction between CRF and age on WMH volume. Participants were 76 adults between the ages of 59 and 77 (mean age = 65.36 years, SD = 3.92) who underwent a maximal graded exercise test and structural brain imaging. Results indicated that age was a predictor of WMH volume (beta = .32, p = .015). However, an age-by-CRF interaction was observed such that higher CRF was associated with lower WMH volume in older participants (beta = -.25, p = .040). Our findings suggest that higher levels of aerobic fitness may protect cerebrovascular health in older adults.


Assuntos
Envelhecimento/patologia , Envelhecimento/fisiologia , Aptidão Cardiorrespiratória/fisiologia , Substância Branca/diagnóstico por imagem , Idoso , Circulação Cerebrovascular/fisiologia , Transtornos Cerebrovasculares/diagnóstico por imagem , Transtornos Cerebrovasculares/patologia , Transtornos Cerebrovasculares/fisiopatologia , Teste de Esforço , Feminino , Humanos , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Neuroimagem , Fatores de Risco , Substância Branca/irrigação sanguínea , Substância Branca/patologia
3.
PLoS One ; 15(9): e0238946, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32956397

RESUMO

BACKGROUND: The origin of low frequency cerebral hemodynamic fluctuations (CHF) in the resting state remains unknown. Breath-by breath O2-CO2 exchange ratio (bER) has been reported to correlate with the cerebrovascular response to brief breath hold challenge at the frequency range of 0.008-0.03Hz in healthy adults. bER is defined as the ratio of the change in the partial pressure of oxygen (ΔPO2) to that of carbon dioxide (ΔPCO2) between end inspiration and end expiration. In this study, we aimed to investigate the contribution of respiratory gas exchange (RGE) metrics (bER, ΔPO2 and ΔPCO2) to low frequency CHF during spontaneous breathing. METHODS: Twenty-two healthy adults were included. We used transcranial Doppler sonography to evaluate CHF by measuring the changes in cerebral blood flow velocity (ΔCBFv) in bilateral middle cerebral arteries. The regional CHF were mapped with blood oxygenation level dependent (ΔBOLD) signal changes using functional magnetic resonance imaging. Temporal features and frequency characteristics of RGE metrics during spontaneous breathing were examined, and the simultaneous measurements of RGE metrics and CHF (ΔCBFv and ΔBOLD) were studied for their correlation. RESULTS: We found that the time courses of ΔPO2 and ΔPCO2 were interdependent but not redundant. The oscillations of RGE metrics were coherent with resting state CHF at the frequency range of 0.008-0.03Hz. Both bER and ΔPO2 were superior to ΔPCO2 in association with CHF while CHF could correlate more strongly with bER than with ΔPO2 in some brain regions. Brain regions with the strongest coupling between bER and ΔBOLD overlapped with many areas of default mode network including precuneus and posterior cingulate. CONCLUSION: Although the physiological mechanisms underlying the strong correlation between bER and CHF are unclear, our findings suggest the contribution of bER to low frequency resting state CHF, providing a novel insight of brain-body interaction via CHF and oscillations of RGE metrics.


Assuntos
Circulação Cerebrovascular/fisiologia , Taxa Respiratória/fisiologia , Adulto , Velocidade do Fluxo Sanguíneo/fisiologia , Encéfalo/fisiologia , Dióxido de Carbono/sangue , Feminino , Voluntários Saudáveis , Hemodinâmica/fisiologia , Humanos , Imagem por Ressonância Magnética/métodos , Masculino , Artéria Cerebral Média/fisiologia , Oxigênio/sangue , Pressão Parcial , Respiração , Descanso/fisiologia , Ultrassonografia Doppler Transcraniana/métodos , Vasodilatação/fisiologia
4.
PLoS One ; 15(9): e0238224, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32881886

RESUMO

OBJECTIVE: We previously showed that MELAS patients have decreased cerebrovascular reactivity (CVR) (p≤ 0.002) and increased cerebral blood flow (CBF) (p<0.0026); changes correlated with disease severity and % mutant mtDNA (inversely for CVR; directly for CBF). We ran a prospective pilot in 3 MELAS sibs (m.3243A>G tRNALeu(UUR)) with variable % mutant blood mtDNA to assess effects of L-Arginine (L-Arg) (single dose and 6-wk steady-state trial) on regional CBF, arterial CVR and neurovascular coupling. METHODS: Patients were studied with 3T MRI using arterial spin labeling (ASL) to measure CBF and changes in % Blood Oxygen Level Dependent (BOLD) signal to changes in arterial partial pressure of CO2 to measure CVR. Task fMRI consisted of an alternating black and white checkerboard to evaluate visual cortex response in MELAS and controls. RESULTS: Following L-Arg, there was restoration of serum Arg (76-230 µM) in MELAS sibs and a trend towards increasing CVR in frontal and corresponding decrease in occipital cortex; CVR was unchanged globally. There was a 29-37% reduction in baseline CBF in one patient following 6 wks of L-Arg. Pre-treatment fMRI activation in response to visual cortex stimulus was markedly decreased in the same patient compared to controls in primary visual striate cortex V1 and extrastriate regions V2 to V5 with a marked increase toward control values following a single dose and 6 wks of L-Arg. CONCLUSION: Proposed "healing" effect may be due to more efficient utilization of energy substrates with increased cellular energy balances and ensuing reduction in signalling pathways that augment flow in the untreated state. CLASSIFICATION OF EVIDENCE: This prospective pilot study provides Class III evidence that oral L-Arginine (100 mg/kg single dose or 100 mg/kg three times daily po X 6 weeks) normalizes resting blood flow from elevated pre-treatment levels in patients with MELAS syndrome, selectively increases their CVR from reduced pre-treatment levels in regions most impaired at the expense of less abnormal regions, and normalizes reduced BOLD fMRI activation in response to visual cortex stimulus. CLINICAL TRIALS.GOV (NIH): NCT01603446.


Assuntos
Arginina/uso terapêutico , Circulação Cerebrovascular/fisiologia , Síndrome MELAS/tratamento farmacológico , Acoplamento Neurovascular/fisiologia , Administração Oral , Adolescente , Arginina/sangue , Arginina/farmacologia , Encéfalo/irrigação sanguínea , Encéfalo/diagnóstico por imagem , Mapeamento Encefálico , Dióxido de Carbono/sangue , Circulação Cerebrovascular/efeitos dos fármacos , Feminino , Humanos , Imagem por Ressonância Magnética , Masculino , Acoplamento Neurovascular/efeitos dos fármacos , Ornitina/sangue , Oxigênio/sangue , Projetos Piloto , Estudos Prospectivos , Resultado do Tratamento , Córtex Visual/efeitos dos fármacos , Adulto Jovem
5.
Neuroepidemiology ; 54(5): 370-374, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32791504

RESUMO

The severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2) causes the coronavirus disease 2019 (COVID-19). It quickly became pandemic, and so did a new concern about COVID-19 infections increasing the risk for cerebrovascular diseases. There is an association between COVID-19 illness in people and acute stroke. Several chemical, mechanical, and/or inflammatory central nervous system pathologies are proposed to explain how this viral infection might induce acute cerebrovascular disease. Timely available evaluation and/or intervention is imperative for patients with concerns about acute cerebrovascular issues.


Assuntos
Betacoronavirus , Encéfalo/virologia , Circulação Cerebrovascular/fisiologia , Infecções por Coronavirus/complicações , Pneumonia Viral/complicações , Acidente Vascular Cerebral/etiologia , Acidente Vascular Cerebral/virologia , Betacoronavirus/metabolismo , Encéfalo/metabolismo , Isquemia Encefálica/etiologia , Isquemia Encefálica/metabolismo , Isquemia Encefálica/virologia , Infecções por Coronavirus/metabolismo , Humanos , Pandemias , Pneumonia Viral/metabolismo , Acidente Vascular Cerebral/metabolismo
6.
Nat Commun ; 11(1): 3851, 2020 07 31.
Artigo em Inglês | MEDLINE | ID: mdl-32737314

RESUMO

Intravascular imaging has emerged as a valuable tool for the treatment of coronary and peripheral artery disease; however, no solution is available for safe and reliable use in the tortuous vascular anatomy of the brain. Endovascular treatment of stroke is delivered under image guidance with insufficient resolution to adequately assess underlying arterial pathology and therapeutic devices. High-resolution imaging, enabling surgeons to visualize cerebral arteries' microstructure and micron-level features of neurovascular devices, would have a profound impact in the research, diagnosis, and treatment of cerebrovascular diseases. Here, we present a neurovascular high-frequency optical coherence tomography (HF-OCT) system, including an imaging console and an endoscopic probe designed to rapidly acquire volumetric microscopy data at a resolution approaching 10 microns in tortuous cerebrovascular anatomies. Using a combination of in vitro, ex vivo, and in vivo models, the feasibility of HF-OCT for cerebrovascular imaging was demonstrated.


Assuntos
Artéria Basilar/diagnóstico por imagem , Artérias Carótidas/diagnóstico por imagem , Artérias Cerebrais/diagnóstico por imagem , Microscopia/métodos , Tomografia de Coerência Óptica/métodos , Artéria Vertebral/diagnóstico por imagem , Angiografia/instrumentação , Angiografia/métodos , Animais , Cadáver , Circulação Cerebrovascular/fisiologia , Humanos , Microscopia/instrumentação , Suínos , Tomografia de Coerência Óptica/instrumentação
7.
Curr Opin Anaesthesiol ; 33(5): 646-650, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32769747

RESUMO

PURPOSE OF REVIEW: Intraoperative hypotension (IOH) may render patients at a risk of cerebral hypoperfusion with decreasing cerebral blood flow (CBF), and lead to postoperative neurological injury. On the basis of the literature in recent years, this review attempts to refine the definition of IOH and evaluate its impact on neurological outcomes. RECENT FINDINGS: Although both absolute and relative blood pressure (BP) thresholds, with or without a cumulative period, have been used in collective clinical studies, no definitive threshold of IOH has been established for neurological complications, including perioperative stroke, postoperative cognitive disorder and delirium. The CBF is jointly modulated by multiple pressure processes (i.e. cerebral pressure autoregulation) and nonpressure processes, including patient, surgical and anaesthesia-related confounding factors. The confounding factors and variability in cerebral pressure autoregulation might impede evaluating the effect of IOH on the neurological outcomes. Furthermore, the majority of the evidence presented in this review are cohort studies, which are weak in demonstrating a cause--effect relationship between IOH and neurological complications. The maintenance of target BP based on the monitoring of regional cerebral oxygen saturation (rScO2) or cerebral pressure autoregulation seems to be associated with the decreased incidence of postoperative neurological complications. SUMMARY: Despite the lack of a known threshold value, IOH is a modifiable risk factor targeted to improve neurological outcomes. Ideal BP management is recommended in order to maintain target BP based on the monitoring of rScO2 or cerebral pressure autoregulation.


Assuntos
Circulação Cerebrovascular/fisiologia , Hipotensão/etiologia , Complicações Intraoperatórias , Complicações Pós-Operatórias , Pressão Sanguínea/fisiologia , Estudos de Coortes , Humanos , Oximetria/métodos , Oxigênio/metabolismo , Procedimentos Cirúrgicos Operatórios
8.
PLoS One ; 15(8): e0234979, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32857778

RESUMO

The present meta-analysis was based on the available studies to determine the potential role of the initial and regional cerebral oxygen saturation (rSO2) in monitoring the efficiency of cardiopulmonary resuscitation (CPR) and predicting the return of spontaneous circulation (ROSC). Three electronic databases of PubMed, Embase, and the Cochrane Library were searched to identify the studies that investigated the role of rSO2 on ROSC in CA patients throughout May 2018. The weighted mean difference (WMD) with 95% confidence interval (CI) was calculated to estimate the pooled effect using a random-effects model. Sensitivity, subgroup analyses, and publication bias were conducted. A total of 13 studies involving 678 CA patients (300 in-hospital (IH) patients, and 378 out-hospital (OH) patients) were included. The summary WMD suggested that ROSC patients were associated with higher initial rSO2 (WMD: 10.10%; 95% CI: 5.66-14.55; P<0.001) and mean rSO2 (WMD: 14.16%; 95% CI: 10.51-17.81; P<0.001) levels during CA and ROSC as compared to the non-ROSC. The results of meta-regression suggested that the male percentage and the location of cardiac arrest might bias the initial or mean rSO2 and the incidence of ROSC. These significant differences were observed in nearly all subsets. The findings of this study suggested that high initial or mean rSO2 levels were both associated with an increased incidence of ROSC in CA patients undergoing CPR. These correlations might be affected by the percentage of males or the location of cardiac arrest, thereby necessitating further large-scale studies to substantiate whether these correlations differ according to gender and the location of cardiac arrest.


Assuntos
Circulação Sanguínea/fisiologia , Parada Cardíaca/fisiopatologia , Oximetria/métodos , Idoso , Idoso de 80 Anos ou mais , Reanimação Cardiopulmonar , Circulação Cerebrovascular/fisiologia , Feminino , Parada Cardíaca/terapia , Humanos , Masculino , Pessoa de Meia-Idade , Parada Cardíaca Extra-Hospitalar/fisiopatologia , Parada Cardíaca Extra-Hospitalar/terapia , Avaliação de Resultados em Cuidados de Saúde , Oxigênio/sangue , Prognóstico , Espectroscopia de Luz Próxima ao Infravermelho/métodos
9.
Neurology ; 95(8): e962-e972, 2020 08 25.
Artigo em Inglês | MEDLINE | ID: mdl-32661101

RESUMO

OBJECTIVE: To determine whether MRI-based cerebrovascular reactivity (CVR) can predict cognitive performance independently of Alzheimer pathologic markers, we studied the relationship between cognition, CVR, and CSF-derived ß-amyloid42 (Aß42) and tau in a group of elderly individuals with mixed Alzheimer and vascular cognitive impairment and dementia. METHODS: This was a cross-sectional study of 72 participants 69 ± 8 years of age consisting of individuals with normal cognition (n = 28) and cognitive impairment (n = 44) (including 36 with mild cognitive impairment [MCI] and 8 with mild dementia). CVR was measured with hypercapnia-MRI. Whole-brain CVR (percent blood oxygen level-dependent per 1 mm Hg Etco2) was used to estimate vasodilatory capacity. Montreal Cognitive Assessment (MoCA) scores, cognitive domains scores, and a global composite cognitive score were obtained. AD biomarkers included CSF assays of Aß42 and tau. RESULTS: Whole-brain CVR was lower in the impaired (mean ± SE, 0.132 ± 0.006%/mm Hg) compared to the normal (0.151 ± 0.007%/mm Hg) group (ß = -0.02%/mm Hg; 95% confidence interval [CI] -0.038 to -0.001). After adjustment for CSF Aß42 and tau, higher whole-brain CVR was associated with better performance on the MoCA (ß = 29.64, 95% CI 9.94-49.34) and with a global composite cognitive score (ß = 4.32, 95% CI 0.05-8.58). When the CVR marker was compared with the Fazekas score based on white matter hyperintensities and vascular risk-score in a single regression model predicting the MoCA score, only CVR revealed a significant effect (ß = 28.09, 95% CI 6.14-50.04), while the other 2 measures were not significant. CONCLUSIONS: CVR was significantly associated with cognitive performance independently of AD pathology. Whole-brain CVR may be a useful biomarker for evaluating cognitive impairment related to vascular disease in older individuals. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that CVR was significantly associated with cognitive performance independent of AD pathology.


Assuntos
Doença de Alzheimer/patologia , Doença de Alzheimer/fisiopatologia , Circulação Cerebrovascular/fisiologia , Idoso , Cognição/fisiologia , Estudos Transversais , Feminino , Humanos , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade
10.
BMJ ; 370: m2397, 2020 07 22.
Artigo em Inglês | MEDLINE | ID: mdl-32699176

RESUMO

OBJECTIVE: To assess the effects of food supplementation on improving working memory and additional measures including cerebral blood flow in children at risk of undernutrition. DESIGN: Randomized controlled trial. SETTING: 10 villages in Guinea-Bissau. PARTICIPANTS: 1059 children aged 15 months to 7 years; children younger than 4 were the primary population. INTERVENTIONS: Supervised isocaloric servings (≈1300 kJ, five mornings each week, 23 weeks) of a new food supplement (NEWSUP, high in plant polyphenols and omega 3 fatty acids, within a wide variety and high fortification of micronutrients, and a high protein content), or a fortified blended food (FBF) used in nutrition programs, or a control meal (traditional rice breakfast). MAIN OUTCOME MEASUREMENTS: The primary outcome was working memory, a core executive function predicting long term academic achievement. Additional outcomes were hemoglobin concentration, growth, body composition, and index of cerebral blood flow (CBFi). In addition to an intention-to-treat analysis, a predefined per protocol analysis was conducted in children who consumed at least 75% of the supplement (820/925, 89%). The primary outcome was assessed by a multivariable Poisson model; other outcomes were assessed by multivariable linear mixed models. RESULTS: Among children younger than 4, randomization to NEWSUP increased working memory compared with the control meal (rate ratio 1.20, 95% confidence interval 1.02 to 1.41, P=0.03), with a larger effect in the per protocol population (1.25, 1.06 to 1.47, P=0.009). NEWSUP also increased hemoglobin concentration among children with anemia (adjusted mean difference 0.65 g/dL, 95% confidence interval 0.23 to 1.07, P=0.003) compared with the control meal, decreased body mass index z score gain (-0.23, -0.43 to -0.02, P=0.03), and increased lean tissue accretion (2.98 cm2, 0.04 to 5.92, P=0.046) with less fat (-5.82 cm2, -11.28 to -0.36, P=0.04) compared with FBF. Additionally, NEWSUP increased CBFi compared with the control meal and FBF in both age groups combined (1.14 mm2/s×10-8, 0.10 to 2.23, P=0.04 for both comparisons). Among children aged 4 and older, NEWSUP had no significant effect on working memory or anemia, but increased lean tissue compared with FBF (4.31 cm2, 0.34 to 8.28, P=0.03). CONCLUSIONS: Childhood undernutrition is associated with long term impairment in cognition. Contrary to current understanding, supplementary feeding for 23 weeks could improve executive function, brain health, and nutritional status in vulnerable young children living in low income countries. Further research is needed to optimize nutritional prescriptions for regenerative improvements in cognitive function, and to test effectiveness in other vulnerable groups. TRIAL REGISTRATION: ClinicalTrials.gov NCT03017209.


Assuntos
Anemia/dietoterapia , Disfunção Cognitiva/dietoterapia , Suplementos Nutricionais/efeitos adversos , Desnutrição/dietoterapia , Estado Nutricional/fisiologia , Sucesso Acadêmico , Anemia/epidemiologia , Estudos de Casos e Controles , Circulação Cerebrovascular/fisiologia , Criança , Pré-Escolar , Cognição/fisiologia , Disfunção Cognitiva/fisiopatologia , Suplementos Nutricionais/estatística & dados numéricos , Feminino , Alimentos Fortificados/provisão & distribução , Guiné-Bissau/epidemiologia , Humanos , Lactente , Análise de Intenção de Tratamento/métodos , Masculino , Desnutrição/epidemiologia , Desnutrição/prevenção & controle , Micronutrientes/provisão & distribução , Medição de Risco
11.
Stroke ; 51(8): 2526-2535, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32640946

RESUMO

BACKGROUND AND PURPOSE: Spreading depolarizations (SDs) are recurrent and ostensibly spontaneous depolarization waves that may contribute to infarct progression after stroke. Somatosensory activation of the metastable peri-infarct tissue triggers peri-infarct SDs at a high rate. METHODS: We directly measured the functional activation threshold to trigger SDs in peri-infarct hot zones using optogenetic stimulation after distal middle cerebral artery occlusion in Thy1-ChR2-YFP mice. RESULTS: Optogenetic activation of peri-infarct tissue triggered SDs at a strikingly high rate (64%) compared with contralateral homotopic cortex (8%; P=0.004). Laser speckle perfusion imaging identified a residual blood flow of 31±2% of baseline marking the metastable tissue with a propensity to develop SDs. CONCLUSIONS: Our data reveal a spatially distinct increase in SD susceptibility in peri-infarct tissue where physiological levels of functional activation are capable of triggering SDs. Given the potentially deleterious effects of peri-infarct SDs, the effect of sensory overstimulation in hyperacute stroke should be examined more carefully.


Assuntos
Infarto Cerebral/fisiopatologia , Circulação Cerebrovascular/fisiologia , Depressão Alastrante da Atividade Elétrica Cortical/fisiologia , Optogenética/métodos , Animais , Infarto Cerebral/genética , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos
12.
Magn Reson Imaging ; 73: 111-117, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32717203

RESUMO

PURPOSE: Arterial spin labeling MRI can quantify the cerebral blood flow (CBF) without exogenous tracer. However, the variation of arterial transit time across different brain regions introduces bias for measuring local CBF, especially for those subjects with long arterial transit time (ATT). Long post-labeling delay (PLD) or multi-PLD methods could mitigate the problem of heterogenous ATT at the expense of the signal-to-noise ratio (SNR). Long-label ASL might address the low SNR problem by increasing the amount of labeled arterial blood. Thus, we hypothesized that with the same relatively long PLD, long-label pCASL may be more robust and reproducible than standard-label pCASL in population with potentially prolonged ATT. The purpose of the study was to investigate the reliability and reproducibility of long-label pCASL in the whole brain and vascular regions of interest in an elderly population, compared with standard-label pCASL. METHOD: Twenty adult volunteers (14 males, 6 females; age, 56.6 ± 17.2 years) were scanned twice on one 3.0 T scanner by standard-label pCASL (label duration (LD) = 1500 ms, PLD = 2000 ms) and long-label pCASL (LD = 3500 ms, PLD = 2000 ms). The intraclass correlation coefficient (ICC), within-subject coefficient of variation (wsCV), random noise and signal coefficient of variation(CoV) were used to assess global and regional reliability and reproducibility. Measurement agreement and difference were compared in different brain regions using correlation coefficient plots and Bland-Altman plots respectively. RESULTS: CBF value measured by long-label pCASL was overall higher than standard-label pCASL in all ROIs. Long-label pCASL had higher ICC than standard-label pCASL in most ROIs, and lower wsCV, random noise and CoV in all ROIs. Regardless of ASL method used, anterior circulation flow territories (ICC, 0.93-0.97; wsCV, 0.03-0.06) had higher CBF reliability and reproducibility than posterior circulation flow territories (ICC, 0.89; wsCV, 0.06-0.08). In all ROIs, the correlation analysis showed higher test-retest agreement (rlong-label > rstandard-label) and the Bland-Altman plots demonstrated lower measurement difference in long-label pCASL. CONCLUSION: The study demonstrated good reliability and reproducibility of long-label pCASL in anterior brain regions in the elderly population. To further improve CBF quantification in a long-ATT population while proper PLD is already used, increasing the label duration may help.


Assuntos
Encéfalo/irrigação sanguínea , Circulação Cerebrovascular/fisiologia , Processamento de Imagem Assistida por Computador/métodos , Imagem por Ressonância Magnética/métodos , Encéfalo/diagnóstico por imagem , Encéfalo/fisiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valores de Referência , Reprodutibilidade dos Testes , Razão Sinal-Ruído , Marcadores de Spin
13.
PLoS One ; 15(7): e0236512, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32706796

RESUMO

OBJECTIVE: To identify abnormalities of regional cerebral blood flow (rCBF) in individuals with obsessive-compulsive disorder (OCD) by conducting a voxel-based analysis of pseudo-continuous arterial spin labeling (pCASL) perfusion images. MATERIALS AND METHODS: This prospective study included 23 OCD patients (nine males, 14 females; age 21-62 years; mean ± SD 37.2 ± 10.7 years) diagnosed based on DSM-IV-TR criteria and 64 healthy controls (27 males, 37 females; age 20-64 years; mean ± SD 38.3 ± 12.8 years). Subjects were recruited from October 2011 to August 2017. Imaging was performed on a 3T scanner. Quantitative rCBF maps generated from pCASL images were co-registered and resliced with the three-dimensional T1-weighted images, and then spatially normalized to a brain template and smoothed. We used statistical nonparametric mapping to assess the differences in rCBF and gray matter volume between the OCD and control groups. The significance level was set at the p-value <0.05 with family-wise error rate correction for multiple comparisons. RESULTS: Compared to the control group, there were significant rCBF reductions in the right putamen, right frontal operculum, left midcingulate cortex, and right temporal pole in the OCD group. There were no significant between-group differences in the gray matter volume. CONCLUSION: The pCASL imaging noninvasively detected physiologically disrupted areas without structural abnormalities in OCD patients. The rCBF reductions observed in these regions in OCD patients could be associated with the pathophysiology of OCD.


Assuntos
Artérias/química , Circulação Cerebrovascular/fisiologia , Imagem por Ressonância Magnética/métodos , Transtorno Obsessivo-Compulsivo/fisiopatologia , Adulto , Encéfalo/diagnóstico por imagem , Mapeamento Encefálico , Estudos de Casos e Controles , Feminino , Humanos , Processamento de Imagem Assistida por Computador , Imageamento Tridimensional , Masculino , Pessoa de Meia-Idade , Transtorno Obsessivo-Compulsivo/diagnóstico por imagem , Estudos Prospectivos , Marcadores de Spin , Adulto Jovem
14.
PLoS One ; 15(7): e0236256, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32716984

RESUMO

INTRODUCTION: Previous studies demonstrate increased intracranial pressure (ICP) during direct laryngoscopy in patients with traumatic brain injury (TBI). Worse outcomes in TBI have been associated with increased ICP. It remains unclear if the same effect occurs during cricothyrotomy. We evaluated changes in cerebral blood flow and hemodynamic changes that occurred during preparation for cricothyrotomy in healthy volunteers. METHODS: An emergency medicine trainee performed routine anatomical procedural palpation with simultaneous transcranial doppler (TCD) measurements of cerebral blood flow velocities (CBFV) from bilateral middle cerebral arteries (MCAs). Mean arterial pressure (MAP) and heart rate (HR) were recorded throughout event. Our primary outcome was changes in pulsatility index (PI) and CBFV by TCD during palpation. TCD measurements were used as a surrogate for ICP. RESULTS: We enrolled 20 healthy volunteers for this study. No significant differences were found in pulsatility index [Right MCA -0.02 (95% confidence interval, -0.09 to 0.06), left MCA -0.02 (95% confidence interval, -0.011 to 0.07)] or mean CBFV [right MCA -0.70 mm/s (95% confidence interval, -10.15 to 8.75) left MCA -1.20 mm/s (95% confidence interval, -10.68 to 8.28)] during palpation. No significant change in HR was found [-1.1 bpm ((95% confidence interval, -2.4 to 0.1)]. A change in MAP was observed [1.3 mmHg (95% confidence interval, -0.1 to 2.4)]. CONCLUSIONS: In healthy individuals, no clinically significant change in cerebral blood flow velocities, ICP, or change heart rate was observed during palpation for cricothyrotomy.


Assuntos
Circulação Cerebrovascular/fisiologia , Voluntários Saudáveis , Palpação , Traqueia/fisiologia , Adulto , Velocidade do Fluxo Sanguíneo/fisiologia , Feminino , Humanos , Masculino , Fluxo Pulsátil
15.
Neurology ; 95(12): e1694-e1705, 2020 09 22.
Artigo em Inglês | MEDLINE | ID: mdl-32675079

RESUMO

OBJECTIVE: Since the strongest risk factor for sudden unexpected death in epilepsy (SUDEP) is frequent bilateral tonic-clonic seizures (BTCS), our aim was to determine whether postictal hypoperfusion in brainstem respiratory centers (BRCs) is more common following tonic-clonic seizures. METHODS: We studied 21 patients with focal epilepsies who underwent perfusion imaging with arterial spin labeling MRI. Subtraction maps of cerebral blood flow were obtained from the postictal and baseline scans. We identified 6 regions of interest in the brainstem that contain key BRCs. Patients were considered to have postictal BRC hypoperfusion if any of the 6 regions of interest were significantly hypoperfused. RESULTS: All 6 patients who experienced BTCS during the study had significant clusters of postictal hypoperfusion in BRCs compared to 7 who had focal impaired awareness seizures (7/15). The association between seizure type studied and the presence of BRC hypoperfusion was significant. Duration of epilepsy and frequency of BTCS were not associated with postictal brainstem hypoperfusion despite also being associated with risk for SUDEP. CONCLUSION: Postictal hypoperfusion in brainstem respiratory centers occurs more often following BTCS than other seizure types, providing a possible explanation for the increased risk of SUDEP in patients who regularly experience BTCS.


Assuntos
Tronco Encefálico/irrigação sanguínea , Convulsões/complicações , Morte Súbita Inesperada na Epilepsia/etiologia , Adulto , Tronco Encefálico/diagnóstico por imagem , Circulação Cerebrovascular/fisiologia , Epilepsias Parciais/complicações , Feminino , Humanos , Imagem por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Neuroimagem/métodos , Imagem de Perfusão/métodos , Fatores de Risco , Adulto Jovem
16.
Neurology ; 95(10): e1333-e1340, 2020 09 08.
Artigo em Inglês | MEDLINE | ID: mdl-32641520

RESUMO

OBJECTIVE: To assess cerebrovascular reactivity in response to a visual task in participants with cerebral amyloid angiopathy (CAA), Alzheimer disease (AD), and mild cognitive impairment (MCI) using fMRI. METHODS: This prospective cohort study included 40 patients with CAA, 22 with AD, 27 with MCI, and 25 healthy controls. Each participant underwent a visual fMRI task using a contrast-reversing checkerboard stimulus. Visual evoked potentials (VEPs) were used to compare visual cortex neuronal activity in 83 participants. General linear models using least-squares means, adjusted for multiple comparisons with the Tukey test, were used to estimate mean blood oxygen level-dependent (BOLD) signal change during the task and VEP differences between groups. RESULTS: After adjustment for age and hypertension, estimated mean BOLD response amplitude was as follows: CAA 1.88% (95% confidence interval [CI] 1.60%-2.15%), AD 2.26% (1.91%-2.61%), MCI 2.15% (1.84%-2.46%), and control 2.65% (2.29%-3.00%). Only patients with CAA differed from controls (p = 0.01). In the subset with VEPs, group was not associated with prolonged latencies or lower amplitudes. Lower BOLD amplitude response was associated with higher white matter hyperintensity (WMH) volumes in CAA (for each 0.1% lower BOLD response amplitude, the WMH volume was 9.2% higher, 95% CI 6.0%-12.4%) but not other groups (p = 0.002 for interaction) when controlling for age and hypertension. CONCLUSIONS: Mean visual BOLD response amplitude was lowest in participants with CAA compared to controls, without differences in VEP latencies and amplitudes. This suggests that the impaired visual BOLD response is due to reduced vascular reactivity in CAA. In contrast to participants with CAA, the visual BOLD response amplitude did not differ between those with AD or MCI and controls.


Assuntos
Doença de Alzheimer/fisiopatologia , Angiopatia Amiloide Cerebral/fisiopatologia , Circulação Cerebrovascular/fisiologia , Disfunção Cognitiva/fisiopatologia , Idoso , Estudos de Coortes , Estudos Transversais , Imagem Ecoplanar , Potenciais Evocados Visuais/fisiologia , Feminino , Humanos , Interpretação de Imagem Assistida por Computador/métodos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Córtex Visual/fisiopatologia
17.
Cochrane Database Syst Rev ; 7: CD012362, 2020 07 07.
Artigo em Inglês | MEDLINE | ID: mdl-32639053

RESUMO

BACKGROUND: Head position during care may affect cerebral haemodynamics and contribute to the development of germinal matrix-intraventricular haemorrhage (GM-IVH) in very preterm infants. Turning the head toward one side may occlude jugular venous drainage while increasing intracranial pressure and cerebral blood volume. It is suggested that cerebral venous pressure is reduced and hydrostatic brain drainage improved if the infant is cared for in the supine 'head midline' position. OBJECTIVES: To assess whether head midline position is more effective than other head positions for preventing (or preventing extension) of GM-IVH in very preterm infants (< 32 weeks' gestation at birth). SEARCH METHODS: We used the standard search strategy of Cochrane Neonatal to search the Cochrane Central Register of Controlled Trials (CENTRAL; 2019, Issue 9), MEDLINE via PubMed (1966 to 12 September 2019), Embase (1980 to 12 September 2019), and the Cumulative Index to Nursing and Allied Health Literature (CINAHL; 1982 to 12 September 2019). We searched clinical trials databases, conference proceedings, and reference lists of retrieved articles. SELECTION CRITERIA: Randomised controlled trials (RCTs) comparing caring for very preterm infants in a supine head midline position versus a prone or lateral decubitus position, or undertaking a strategy of regular position change, or having no prespecified position. We included trials enrolling infants with existing GM-IVH and planned to assess extension of haemorrhage in a subgroup of infants. We planned to analyse horizontal (flat) versus head elevated positions separately for all body positions. DATA COLLECTION AND ANALYSIS: We used standard methods of Cochrane Neonatal. For each of the included trials, two review authors independently extracted data and assessed risk of bias. The primary outcomes were GM-IVH, severe IVH, and neonatal death. We evaluated treatment effects using a fixed-effect model with risk ratio (RR) for categorical data; and mean, standard deviation (SD), and mean difference (MD) for continuous data. We used the GRADE approach to assess the certainty of evidence. MAIN RESULTS: Three RCTs, with a total of 290 infants (either < 30 weeks' gestational age or < 1000 g body weight), met the inclusion criteria. Two trials compared supine midline head position versus head rotated 90° with the cot flat. One trial compared supine midline head position versus head rotated 90° with the bed tilted at 30°. We found no trials that compared supine versus prone midline head position. Meta-analysis of three trials (290 infants) did not show an effect on rates of GM-IVH (RR 1.11, 95% confidence interval (CI) 0.78 to 1.56; I² = 0%) and severe IVH (RR 0.71, 95% CI 0.37 to 1.33; I² = 0%). Neonatal mortality (RR 0.49, 95% CI 0.25 to 0.93; I² = 0%; RD -0.09, 95% CI -0.16 to -0.01) and mortality until hospital discharge (typical RR 0.50, 95% CI 0.28 to 0.90; I² = 0%; RD -0.10, 95% CI -0.18 to -0.02) were lower in the supine midline head position. The certainty of the evidence was very low for all outcomes because of limitations in study design and imprecision of estimates. We identified one ongoing study. AUTHORS' CONCLUSIONS: We found few trial data on the effects of head midline position on GM-IVH in very preterm infants. Although meta-analyses suggest that mortality might be reduced, the certainty of the evidence is very low and it is unclear whether any effect is due to cot tilting (a co-intervention in one trial). Further high-quality RCTs would be needed to resolve this uncertainty.


Assuntos
Hemorragia Cerebral Intraventricular/prevenção & controle , Cabeça , Doenças do Prematuro/prevenção & controle , Posicionamento do Paciente/métodos , Decúbito Dorsal , Leitos , Hemorragia Cerebral Intraventricular/epidemiologia , Hemorragia Cerebral Intraventricular/etiologia , Circulação Cerebrovascular/fisiologia , Humanos , Lactente , Mortalidade Infantil , Recém-Nascido , Recém-Nascido Prematuro , Doenças do Prematuro/epidemiologia , Doenças do Prematuro/etiologia , Viés de Publicação , Ensaios Clínicos Controlados Aleatórios como Assunto , Retinopatia da Prematuridade/epidemiologia , Rotação
18.
J Vis Exp ; (159)2020 05 27.
Artigo em Inglês | MEDLINE | ID: mdl-32538897

RESUMO

To obtain a comprehensive understanding of the human brain, utilization of cerebral blood flow (CBF) as a source of contrast is desired because it is a key hemodynamic parameter related to cerebral oxygen supply. Resting state low frequency fluctuations based on oxygenation contrast have been shown to provide correlations between functionally connected regions. The presented protocol uses optical diffuse correlation spectroscopy (DCS) to assess blood flow-based resting state functional connectivity (RSFC) in the human brain. Results of CBF-based RSFC in human frontal cortex indicate that intra-regional RSFC is significantly higher in the left and right cortices compared to inter-regional RSFC in both cortices. This protocol should be of interest to researchers who employ multi-modal imaging techniques to study human brain function, especially in the pediatric population.


Assuntos
Encéfalo/irrigação sanguínea , Circulação Cerebrovascular , Análise Espectral , Adulto , Encéfalo/fisiologia , Córtex Cerebral/irrigação sanguínea , Córtex Cerebral/fisiologia , Circulação Cerebrovascular/fisiologia , Lobo Frontal/irrigação sanguínea , Lobo Frontal/fisiologia , Humanos
19.
J Anesth Hist ; 6(2): 98-100, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32593385

RESUMO

In the 1940s, Seymour S. Kety and Carl F. Schmidt measured cerebral blood flow in awake humans by means of subanesthetic doses of inhaled nitrous oxide. The inhalation route obviated the need for an arterial injection of the indicator, and nitrous oxide had virtues of metabolic inertness, rapid diffusion through the blood-brain barrier, comparable blood and brain solubility, and ease of analytical detection. The technique was also applied to the heart. Follow-up work by Kety contributed to the development of brain scanning methods.


Assuntos
Circulação Cerebrovascular/fisiologia , Óxido Nitroso/metabolismo , Administração por Inalação , História do Século XX , Humanos , Hiperventilação/fisiopatologia , Óxido Nitroso/administração & dosagem , Estados Unidos
20.
Nat Commun ; 11(1): 3012, 2020 06 15.
Artigo em Inglês | MEDLINE | ID: mdl-32541656

RESUMO

The complex relationship between specific hippocampal oscillation frequency deficit and cognitive dysfunction in the ischemic brain is unclear. Here, using a mouse two-vessel occlusion (2VO) cerebral ischemia model, we show that visual stimulation with a 40 Hz light flicker drove hippocampal CA1 slow gamma and restored 2VO-induced reduction in CA1 slow gamma power and theta-low gamma phase-amplitude coupling, but not those of the high gamma. Low gamma frequency lights at 30 Hz, 40 Hz, and 50 Hz, but not 10 Hz, 80 Hz, and arrhythmic frequency light, were protective against degenerating CA1 neurons after 2VO, demonstrating the importance of slow gamma in cognitive functions after cerebral ischemia. Mechanistically, 40 Hz light flicker enhanced RGS12-regulated CA3-CA1 presynaptic N-type calcium channel-dependent short-term synaptic plasticity and associated postsynaptic long term potentiation (LTP) after 2VO. These results support a causal relationship between CA1 slow gamma and cognitive dysfunctions in the ischemic brain.


Assuntos
Região CA1 Hipocampal/fisiologia , Potenciais Pós-Sinápticos Excitadores/fisiologia , Ritmo Gama/fisiologia , Plasticidade Neuronal/fisiologia , Neurônios/fisiologia , Animais , Isquemia Encefálica/fisiopatologia , Região CA1 Hipocampal/irrigação sanguínea , Circulação Cerebrovascular/fisiologia , Estimulação Elétrica , Masculino , Aprendizagem em Labirinto/fisiologia , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Atividade Motora/fisiologia , Estimulação Luminosa
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