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1.
J Cereb Blood Flow Metab ; 44(6): 1039-1052, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38190981

RESUMO

Cerebral oxygen metabolism is altered in relapsing-remitting multiple sclerosis (RRMS), possibly a result of disease related cerebral atrophy with subsequent decreased oxygen demand. However, MS inflammation can also inhibit brain metabolism. Therefore, we measured cerebral blood flow (CBF) and cerebral metabolic rate of oxygen (CMRO2) using MRI phase contrast mapping and susceptibility-based oximetry in 44 patients with early RRMS and 36 healthy controls. Cerebral atrophy and white matter lesion load were assessed from high-resolution structural MRI. Expanded Disability Status Scale (EDSS) scores were collected from medical records. The CMRO2 was significantly lower in patients (-15%, p = 0.002) and decreased significantly with age in patients relative to the controls (-1.35 µmol/100 g/min/year, p = 0.036). The lower CMRO2 in RRMS was primarily driven by a higher venous oxygen saturation in the sagittal sinus (p = 0.007) and not a reduction in CBF (p = 0.69). There was no difference in cerebral atrophy between the groups, and no correlation between CMRO2 and MS lesion volume or EDSS score. Therefore, the progressive CMRO2 decline observed before the occurrence of significant cerebral atrophy and despite adequate CBF supports emerging evidence of dysfunctional cellular respiration as a potential pathogenic mechanism and therapeutic target in RRMS.


Assuntos
Circulação Cerebrovascular , Imageamento por Ressonância Magnética , Consumo de Oxigênio , Humanos , Adulto , Feminino , Masculino , Consumo de Oxigênio/fisiologia , Circulação Cerebrovascular/fisiologia , Pessoa de Meia-Idade , Esclerose Múltipla Recidivante-Remitente/metabolismo , Esclerose Múltipla Recidivante-Remitente/diagnóstico por imagem , Esclerose Múltipla Recidivante-Remitente/patologia , Esclerose Múltipla Recidivante-Remitente/fisiopatologia , Encéfalo/metabolismo , Encéfalo/diagnóstico por imagem , Envelhecimento/metabolismo , Atrofia , Oxigênio/metabolismo , Oxigênio/sangue , Esclerose Múltipla/metabolismo , Esclerose Múltipla/patologia , Esclerose Múltipla/diagnóstico por imagem , Adulto Jovem
2.
J Cereb Blood Flow Metab ; 43(3): 460-475, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36369740

RESUMO

The healthy cerebral perfusion demonstrates a homogenous distribution of capillary transit times. A disruption of this homogeneity may inhibit the extraction of oxygen. A high degree of capillary transit time heterogeneity (CTH) describes that some capillaries have very low blood flows, while others have excessively high blood flows and consequently short transit times. Very short transit times could hinder the oxygen extraction due to insufficient time for diffusion of oxygen into the tissue. CTH could be a consequence of cerebral vessel disease. We examined whether patients with cerebral steno-occlusive vessel disease demonstrate high CTH and if elevation of cerebral blood flow (CBF) by administration of acetazolamide (ACZ) increases the cerebral metabolic rate of oxygen (CMRO2), or if some patients demonstrate reduced CMRO2 related to detrimental CTH. Thirty-four patients and thirty-one healthy controls participated. Global CBF and CMRO2 were acquired using phase-contrast MRI. Regional brain maps of CTH were acquired using dynamic contrast-enhanced MRI. Patients with impaired cerebrovascular reserve capacity demonstrated elevated CTH and a significant reduction of CMRO2 after administration of ACZ, which could be related to high CTH. Impaired oxygen extraction from CTH could be a contributing part of the declining brain health observed in patients with cerebral vessel disease.


Assuntos
Encéfalo , Capilares , Humanos , Capilares/fisiologia , Encéfalo/irrigação sanguínea , Imageamento por Ressonância Magnética , Hemodinâmica , Oxigênio/metabolismo , Acetazolamida , Circulação Cerebrovascular/fisiologia , Consumo de Oxigênio/fisiologia
3.
J Cereb Blood Flow Metab ; 41(3): 604-616, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-32423331

RESUMO

Migraine is a complex disorder, involving peripheral and central brain structures, where mechanisms and site of attack initiation are an unresolved puzzle. While abnormal pontine neuronal activation during migraine attacks has been reported, exact implication of this finding is unknown. Evidence suggests an important role of glutamate in migraine, implying a possible association of pontine hyperactivity to increased glutamate levels. Migraine without aura patients were scanned during attacks after calcitonin gene-related peptide and sildenafil in a double-blind, randomized, double-dummy, cross-over design, on two separate study days, by proton magnetic resonance spectroscopy and pseudo-continuous arterial spin labeling at 3T. Headache characteristics were recorded until 24 h after drug administrations. Twenty-six patients were scanned during migraine, yielding a total of 41 attacks. Cerebral blood flow increased in dorsolateral pons, ipsilateral to pain side during attacks, compared to outside attacks (13.6%, p = 0.009). Glutamate levels in the same area remained unchanged during attacks (p = 0.873), while total creatine levels increased (3.5%, p = 0.041). In conclusion, dorsolateral pontine activation during migraine was not associated with higher glutamate levels. However, the concurrently increased total creatine levels may suggest an altered energy metabolism, which should be investigated in future studies to elucidate the role of pons in acute migraine.


Assuntos
Ácido Glutâmico/metabolismo , Imageamento por Ressonância Magnética , Transtornos de Enxaqueca/patologia , Ponte/metabolismo , Espectroscopia de Prótons por Ressonância Magnética , Adulto , Artérias/química , Artérias/fisiopatologia , Peptídeo Relacionado com Gene de Calcitonina/farmacologia , Peptídeo Relacionado com Gene de Calcitonina/uso terapêutico , Circulação Cerebrovascular/efeitos dos fármacos , Circulação Cerebrovascular/fisiologia , Creatina/metabolismo , Método Duplo-Cego , Metabolismo Energético/efeitos dos fármacos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Transtornos de Enxaqueca/tratamento farmacológico , Ponte/irrigação sanguínea , Ponte/fisiopatologia , Citrato de Sildenafila/farmacologia , Citrato de Sildenafila/uso terapêutico , Marcadores de Spin , Vasodilatadores/farmacologia , Vasodilatadores/uso terapêutico , Adulto Jovem
4.
J Cereb Blood Flow Metab ; 41(6): 1328-1337, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33028147

RESUMO

Glibenclamide inhibits sulfonylurea receptor (SUR), which regulates several ion channels including SUR1-transient receptor potential melastatin 4 (SUR1-TRPM4) channel and ATP-sensitive potassium (KATP) channel. Stroke upregulates SURl-TRPM4 channel, which causes a rapid edema formation and brain swelling. Glibenclamide may antagonize the formation of cerebral edema during stroke. Preclinical studies showed that glibenclamide inhibits KATP channel-induced vasodilation without altering the basal vascular tone. The in vivo human cerebrovascular effects of glibenclamide have not previously been investigated.In a randomized, double-blind, placebo-controlled, three-way cross-over study, we used advanced 3 T MRI methods to investigate the effects of glibenclamide and KATP channel opener levcromakalim on mean global cerebral blood flow (CBF) and intra- and extracranial artery circumferences in 15 healthy volunteers. Glibenclamide administration did not alter the mean global CBF and the basal vascular tone. Following levcromakalim infusion, we observed a 14% increase of the mean global CBF and an 8% increase of middle cerebral artery (MCA) circumference, and glibenclamide did not attenuate levcromakalim-induced vascular changes. Collectively, the findings demonstrate the vital role of KATP channels in cerebrovascular hemodynamic and indicate that glibenclamide does not inhibit the protective effects of KATP channel activation during hypoxia and ischemia-induced brain injury.


Assuntos
Circulação Cerebrovascular/efeitos dos fármacos , Cromakalim/farmacologia , Glibureto/farmacologia , Canais KATP/metabolismo , Adulto , Artérias Cerebrais/efeitos dos fármacos , Artérias Cerebrais/metabolismo , Estudos Cross-Over , Método Duplo-Cego , Feminino , Voluntários Saudáveis , Humanos , Canais KATP/efeitos dos fármacos , Imageamento por Ressonância Magnética/métodos , Masculino , Adulto Jovem
5.
J Cereb Blood Flow Metab ; 40(2): 341-353, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-30540217

RESUMO

The aging brain is associated with atrophy along with functional and metabolic changes. In this study, we examined age-related changes in resting brain functions and the vulnerability of brain physiology to hypoxic exposure in humans in vivo. Brain functions were examined in 81 healthy humans (aged 18-62 years) by acquisitions of gray and white matter volumes, cerebral blood flow, cerebral oxygen consumption, and concentrations of lactate, N-acetylaspartate, and glutamate+glutamine using magnetic resonance imaging and spectroscopy. We observed impaired cerebral blood flow reactivity in response to inhalation of hypoxic air (p = 0.029) with advancing age along with decreased cerebral oxygen consumption (p = 0.036), and increased lactate concentration (p = 0.009), indicating tissue hypoxia and impaired metabolism. Diminished resilience to hypoxia and consequently increased vulnerability to metabolic stress could be a key part of declining brain health with age. Furthermore, we observed increased resting cerebral lactate concentration with advancing age (p = 0.007), which might reflect inhibited brain clearance of waste products.


Assuntos
Envelhecimento/metabolismo , Circulação Cerebrovascular , Hipóxia Encefálica , Imageamento por Ressonância Magnética , Substância Branca , Adolescente , Adulto , Feminino , Humanos , Hipóxia Encefálica/diagnóstico por imagem , Hipóxia Encefálica/metabolismo , Hipóxia Encefálica/fisiopatologia , Ácido Láctico/metabolismo , Masculino , Pessoa de Meia-Idade , Consumo de Oxigênio , Projetos Piloto , Substância Branca/irrigação sanguínea , Substância Branca/metabolismo , Substância Branca/fisiopatologia
6.
J Cereb Blood Flow Metab ; 40(8): 1621-1633, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-31500521

RESUMO

Arterial spin labelling (ASL) is a non-invasive magnetic resonance imaging (MRI) technique that may provide fully quantitative regional cerebral blood flow (rCBF) images. However, before its application in clinical routine, ASL needs to be validated against the clinical gold standard, 15O-H2O positron emission tomography (PET). We aimed to compare the two techniques by performing simultaneous quantitative ASL-MRI and 15O-H2O-PET examinations in a hybrid PET/MRI scanner. Duplicate rCBF measurements were performed in healthy young subjects (n = 14) in rest, during hyperventilation, and after acetazolamide (post-ACZ), yielding 63 combined PET/MRI datasets in total. Average global CBF by ASL-MRI and 15O-H2O-PET was not significantly different in any state (40.0 ± 6.5 and 40.6 ± 4.1 mL/100 g/min, respectively in rest, 24.5 ± 5.1 and 23.4 ± 4.8 mL/100 g/min, respectively, during hyperventilation, and 59.1 ± 10.4 and 64.7 ± 10.0 mL/100 g/min, respectively, post-ACZ). Overall, strong correlation between the two methods was found across all states (slope = 1.01, R2 = 0.82), while the correlations within individual states and of reactivity measures were weaker, in particular in rest (R2 = 0.05, p = 0.03). Regional distribution was similar, although ASL yielded higher perfusion and absolute reactivity in highly vascularized areas. In conclusion, ASL-MRI and 15O-H2O-PET measurements of rCBF are highly correlated across different perfusion states, but with variable correlation within and between hemodynamic states, and systematic differences in regional distribution.


Assuntos
Encéfalo/irrigação sanguínea , Encéfalo/diagnóstico por imagem , Circulação Cerebrovascular/fisiologia , Imageamento por Ressonância Magnética/métodos , Tomografia por Emissão de Pósitrons/métodos , Acetazolamida/administração & dosagem , Adulto , Voluntários Saudáveis , Humanos , Radioisótopos de Oxigênio , Perfusão , Compostos Radiofarmacêuticos , Descanso , Marcadores de Spin , Água , Adulto Jovem
7.
J Cereb Blood Flow Metab ; 39(5): 782-793, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-29333914

RESUMO

In this study, a new hybrid PET/MRI method for quantitative regional cerebral blood flow (rCBF) measurements in healthy newborn infants was assessed and the low values of rCBF in white matter previously obtained by arterial spin labeling (ASL) were tested. Four healthy full-term newborn subjects were scanned in a PET/MRI scanner during natural sleep after median intravenous injection of 14 MBq 15O-water. Regional CBF was quantified using a one-tissue-compartment model employing an image-derived input function (IDIF) from the left ventricle. PET rCBF showed the highest values in the thalami, mesencephalon and brain stem and the lowest in cortex and unmyelinated white matter. The average global CBF was 17.8 ml/100 g/min. The average frontal and occipital unmyelinated white matter CBF was 10.3 ml/100 g/min and average thalamic CBF 31.3 ml/100 g/min. The average white matter/thalamic ratio CBF was 0.36, significantly higher than previous ASL data. The rCBF ASL measurements were all unsuccessful primarily owing to subject movement. In this study, we demonstrated for the first time, a minimally invasive PET/MRI method using low activity 15O-water PET for quantitative rCBF assessment in unsedated healthy newborn infants and found a white/grey matter CBF ratio similar to that of the adult human brain.


Assuntos
Encéfalo/irrigação sanguínea , Circulação Cerebrovascular , Imageamento por Ressonância Magnética/métodos , Tomografia por Emissão de Pósitrons/métodos , Feminino , Humanos , Recém-Nascido , Masculino , Radioisótopos de Oxigênio/análise , Marcadores de Spin , Água/análise
8.
J Cereb Blood Flow Metab ; 39(4): 680-689, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-28686073

RESUMO

Experimentally induced hypoxia triggers migraine and aura attacks in patients suffering from migraine with aura (MA). We investigated the blood oxygenation level-dependent (BOLD) signal response to visual stimulation during hypoxia in MA patients and healthy volunteers. In a randomized double-blind crossover study design, 15 MA patients were allocated to 180 min of normobaric poikilocapnic hypoxia (capillary oxygen saturation 70-75%) or sham (normoxia) on two separate days and 14 healthy volunteers were exposed to hypoxia. The BOLD functional MRI (fMRI) signal response to visual stimulation was measured in the visual cortex ROIs V1-V5. Total cerebral blood flow (CBF) was calculated by measuring the blood velocity in the internal carotid arteries and the basilar artery using phase-contrast mapping (PCM) MRI. Hypoxia induced a greater decrease in BOLD response to visual stimulation in V1-V4 in MA patients compared to controls. There was no group difference in hypoxia-induced total CBF increase. In conclusion, the study demonstrated a greater hypoxia-induced decrease in BOLD response to visual stimulation in MA patients. We suggest this may represent a hypoxia-induced change in neuronal excitability or abnormal vascular response to visual stimulation, which may explain the increased sensibility to hypoxia in these patients leading to migraine attacks.


Assuntos
Circulação Cerebrovascular , Hipóxia/fisiopatologia , Enxaqueca com Aura/fisiopatologia , Adolescente , Adulto , Feminino , Humanos , Angiografia por Ressonância Magnética , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Oxigênio/sangue , Estimulação Luminosa , Adulto Jovem
9.
J Cereb Blood Flow Metab ; 39(5): 834-848, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-29099292

RESUMO

The goal of the present study was to examine the cerebral metabolism and vascular reactivity during extended breath-holds (ranging from 2 min 32 s to 7 min 0 s) and during a hypoxic challenge in freedivers and non-diver controls. Magnetic resonance imaging was used to measure the global cerebral blood flow (CBF) and metabolic rate of oxygen (CMRO2), and magnetic resonance spectroscopy was used to measure the cerebral lactate, glutamate+glutamine, N-acetylaspartate and phosphocreatine+creatine concentrations in the occipital lobe. Fifteen freedivers and seventeen non-diver controls participated. The freedivers showed remarkable increases in CBF (107%) during the breath-holds, compensating for arterial desaturation, and sustained cerebral oxygen delivery (CDO2). CMRO2 was unaffected throughout the breath-holds. During the hypoxic challenge, the freedivers had larger increases in blood flow in the sagittal sinus than the non-divers, and could sustain normal CDO2. No differences were found in lactate production, global CBF or CMRO2. We conclude that the mechanism for sustaining brain function during breath-holding in freedivers involves an extraordinary increase in perfusion, and that freedivers present evidence for higher cerebrovascular reactivity, but not for higher lactate-producing glycolysis during a hypoxic challenge compared to controls.


Assuntos
Encéfalo/metabolismo , Suspensão da Respiração , Circulação Cerebrovascular , Hipóxia/metabolismo , Oxigênio/metabolismo , Adulto , Encéfalo/irrigação sanguínea , Mergulho , Feminino , Glicólise , Humanos , Ácido Láctico/metabolismo , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Consumo de Oxigênio , Adulto Jovem
10.
J Cereb Blood Flow Metab ; 39(12): 2368-2378, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-30200799

RESUMO

Phase-contrast mapping (PCM) magnetic resonance imaging (MRI) provides easy-access non-invasive quantification of global cerebral blood flow (gCBF) but its accuracy in altered perfusion states is not established. We aimed to compare paired PCM MRI and 15O-H2O positron emission tomography (PET) measurements of gCBF in different perfusion states in a single scanning session. Duplicate combined gCBF PCM-MRI and 15O-H2O PET measurements were performed in the resting condition, during hyperventilation and after acetazolamide administration (post-ACZ) using a 3T hybrid PET/MR system. A total of 62 paired gCBF measurements were acquired in 14 healthy young male volunteers. Average gCBF in resting state measured by PCM-MRI and 15O-H2O PET were 58.5 ± 10.7 and 38.6 ± 5.7 mL/100 g/min, respectively, during hyperventilation 33 ± 8.6 and 24.7 ± 5.8 mL/100 g/min, respectively, and post-ACZ 89.6 ± 27.1 and 57.3 ± 9.6 mL/100 g/min, respectively. On average, gCBF measured by PCM-MRI was 49% higher compared to 15O-H2O PET. A strong correlation between the two methods across all states was observed (R2 = 0.72, p < 0.001). Bland-Altman analysis suggested a perfusion dependent relative bias resulting in higher relative difference at higher CBF values. In conclusion, measurements of gCBF by PCM-MRI in healthy volunteers show a strong correlation with 15O-H2O PET, but are associated with a large and non-linear perfusion-dependent difference.


Assuntos
Encéfalo , Circulação Cerebrovascular/fisiologia , Angiografia por Ressonância Magnética , Radioisótopos de Oxigênio/administração & dosagem , Tomografia por Emissão de Pósitrons , Adolescente , Adulto , Velocidade do Fluxo Sanguíneo , Encéfalo/irrigação sanguínea , Encéfalo/diagnóstico por imagem , Humanos , Masculino , Radioisótopos de Oxigênio/farmacocinética
11.
J Cereb Blood Flow Metab ; 37(4): 1398-1409, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-27342321

RESUMO

Kinetic analysis of 18F-fluorodeoxyglucose positron emission tomography data requires an accurate knowledge the arterial input function. The gold standard method to measure the arterial input function requires collection of arterial blood samples and is an invasive method. Measuring an image derived input function is a non-invasive alternative but is challenging due to partial volume effects caused by the limited spatial resolution of the positron emission tomography scanners. In this work, a practical image derived input function extraction method is presented, which only requires segmentation of the carotid arteries from MR images. The simulation study results showed that at least 92% of the true intensity could be recovered after the partial volume correction. Results from 19 subjects showed that the mean cerebral metabolic rate of glucose calculated using arterial samples and partial volume corrected image derived input function were 26.9 and 25.4 mg/min/100 g, respectively, for the grey matter and 7.2 and 6.7 mg/min/100 g for the white matter. No significant difference in the estimated cerebral metabolic rate of glucose values was observed between arterial samples and corrected image derived input function (p > 0.12 for grey matter and white matter). Hence, the presented image derived input function extraction method can be a practical alternative to noninvasively analyze dynamic 18F-fluorodeoxyglucose data without the need for blood sampling.


Assuntos
Encéfalo/diagnóstico por imagem , Artérias Carótidas/diagnóstico por imagem , Interpretação de Imagem Assistida por Computador/métodos , Neuroimagem/métodos , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Adulto , Encéfalo/irrigação sanguínea , Artérias Carótidas/fisiologia , Fluordesoxiglucose F18 , Humanos , Cinética , Masculino , Imagens de Fantasmas , Compostos Radiofarmacêuticos , Adulto Jovem
12.
J Headache Pain ; 15: 25, 2014 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-24886137

RESUMO

BACKGROUND: Non-invasive magnetic resonance angiography (MRA) has facilitated repeated measurements of human cranial arteries in several headache and migraine studies. To ensure comparability across studies the same automated analysis software has been used, but the intra- and interobserver, day-to-day and side-to-side variations have not yet been published. We hypothesised that the observer related, side-to-side, and day-to-day variations would be less than 10%. METHODS: Ten female participants were studied using high-resolution MRA on two study days separated by at least one week. Using the automated LKEB-MRA vessel wall analysis software arterial circumferences were measured by blinded observers. Each artery was analysed twice by each of the two different observers. The primary endpoints were to determine the intraclass correlation coefficient (ICC) and intra- an inter-observer, the day-to-day, and side-to-side variations of the circumference of the middle meningeal (MMA) and middle cerebral (MCA) arteries. RESULTS: We found an excellent intra- and interobserver agreement for the MMA (ICC: 0.909-0.987) and for the MCA (ICC: 0.876-0.949). The coefficient of variance within observers was ≤1.8% for MMA and ≤3.1% for MCA; between observers ≤3.4% (MMA) and ≤4.1% (MCA); between days ≤6.0% (MMA) and ≤8.0% (MCA); between sides ≤9.4% (MMA) and ≤6.5% (MCA). CONCLUSION: The present study demonstrates a low (<5%) inter- and intraobserver variation using the automated LKEB-MRA vessel wall analysis software. Furthermore, the study also suggests that the day-to-day and side-to-side variations of the MMA and MCA circumferences are less than 10%.


Assuntos
Artérias Cerebrais/diagnóstico por imagem , Angiografia por Ressonância Magnética/normas , Transtornos de Enxaqueca/diagnóstico por imagem , Adulto , Artérias Cerebrais/fisiopatologia , Feminino , Humanos , Angiografia por Ressonância Magnética/métodos , Transtornos de Enxaqueca/epidemiologia , Transtornos de Enxaqueca/fisiopatologia , Variações Dependentes do Observador , Radiografia , Adulto Jovem
13.
Cephalalgia ; 32(2): 140-9, 2012 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-22174350

RESUMO

AIM: To explore a possible relationship between vasodilatation and delayed headache we examined the effect of pituitary adenylate cyclase-activating polypeptide-38 (PACAP38) on the middle meningeal artery (MMA) and middle cerebral artery (MCA) using high resolution magnetic resonance angiography (MRA). METHODS: In a double-blind, randomized, placebo-controlled study 14 healthy volunteers were scanned repeatedly after infusion (20 min) of 10 pmol/kg/min PACAP38 or placebo. In addition, four participants were scanned following subcutaneous sumatriptan (6 mg). RESULTS: We found significant dilatation of the MMA (p = 0.00001), but not of the MCA (p = 0.50) after PACAP38. There was no change after placebo (p > 0.40). Vasodilatation (range 16-23%) lasted more than 5 h. Sumatriptan selectively contracted the MMA by 12.3% (p = 0.043). CONCLUSION: PACAP38-induced headache is associated with prolonged dilatation of the MMA but not of the MCA. Sumatriptan relieves headache in parallel with contraction of the MMA but not of the MCA.


Assuntos
Cefaleia/induzido quimicamente , Cefaleia/fisiopatologia , Artérias Meníngeas/efeitos dos fármacos , Polipeptídeo Hipofisário Ativador de Adenilato Ciclase/efeitos adversos , Vasodilatação/efeitos dos fármacos , Adulto , Pressão Sanguínea/efeitos dos fármacos , Dióxido de Carbono/metabolismo , Feminino , Cefaleia/tratamento farmacológico , Frequência Cardíaca/efeitos dos fármacos , Humanos , Angiografia por Ressonância Magnética , Masculino , Artérias Meníngeas/fisiologia , Artéria Cerebral Média/efeitos dos fármacos , Artéria Cerebral Média/fisiologia , Placebos , Sumatriptana/administração & dosagem , Fatores de Tempo , Vasoconstritores/administração & dosagem , Vasodilatadores/efeitos adversos , Adulto Jovem
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