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BACKGROUND: The cortical microvascular cerebral blood flow response (CBF) to different changes in head-of-bed (HOB) position has been shown to be altered in acute ischemic stroke (AIS) by diffuse correlation spectroscopy (DCS) technique. However, the relationship between these relative ΔCBF changes and associated systemic blood pressure changes has not been studied, even though blood pressure is a major driver of cerebral blood flow. METHODS: Transcranial DCS data from four studies measuring bilateral frontal microvascular cerebral blood flow in healthy controls (n = 15), patients with asymptomatic severe internal carotid artery stenosis (ICA, n = 27), and patients with acute ischemic stroke (AIS, n = 72) were aggregated. DCS-measured CBF was measured in response to a short head-of-bed (HOB) position manipulation protocol (supine/elevated/supine, 5 min at each position). In a sub-group (AIS, n = 26; ICA, n = 14; control, n = 15), mean arterial pressure (MAP) was measured dynamically during the protocol. RESULTS: After elevated positioning, DCS CBF returned to baseline supine values in controls (p = 0.890) but not in patients with AIS (9.6% [6.0,13.3], mean 95% CI, p < 0.001) or ICA stenosis (8.6% [3.1,14.0], p = 0.003)). MAP in AIS patients did not return to baseline values (2.6 mmHg [0.5, 4.7], p = 0.018), but in ICA stenosis patients and controls did. Instead ipsilesional but not contralesional CBF was correlated with MAP (AIS 6.0%/mmHg [- 2.4,14.3], p = 0.038; ICA stenosis 11.0%/mmHg [2.4,19.5], p < 0.001). CONCLUSIONS: The observed associations between ipsilateral CBF and MAP suggest that short HOB position changes may elicit deficits in cerebral autoregulation in cerebrovascular disorders. Additional research is required to further characterize this phenomenon.
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Presión Arterial , Estenosis Carotídea/fisiopatología , Circulación Cerebrovascular , Accidente Cerebrovascular Isquémico/fisiopatología , Posición Supina/fisiología , Adulto , Anciano , Anciano de 80 o más Años , Velocidad del Flujo Sanguíneo/fisiología , Presión Sanguínea , Isquemia Encefálica/fisiopatología , Estudios de Casos y Controles , Femenino , Inclinación de Cabeza/fisiología , Hemodinámica , Homeostasis , Humanos , Masculino , Persona de Mediana Edad , Accidente Cerebrovascular/fisiopatologíaRESUMEN
BACKGROUND AND PURPOSE: A primary goal of acute ischemic stroke (AIS) management is to maximize perfusion in the affected region and surrounding ischemic penumbra. However, interventions to maximize perfusion, such as flat head-of-bed (HOB) positioning, are currently prescribed empirically. Bedside monitoring of cerebral blood flow (CBF) allows the effects of interventions such as flat HOB to be monitored and may ultimately be used to guide clinical management. METHODS: Cerebral perfusion was measured during HOB manipulations in 17 patients with unilateral AIS affecting large cortical territories in the anterior circulation. Simultaneous measurements of frontal CBF and arterial flow velocity were performed with diffuse correlation spectroscopy and transcranial Doppler ultrasound, respectively. Results were analyzed in the context of available clinical data and a previous study. RESULTS: Frontal CBF, averaged over the patient cohort, decreased by 17% (P=0.034) and 15% (P=0.011) in the ipsilesional and contralesional hemispheres, respectively, when HOB was changed from flat to 30°. Significant (cohort-averaged) changes in blood velocity were not observed. Individually, varying responses to HOB manipulation were observed, including paradoxical increases in CBF with increasing HOB angle. Clinical features, stroke volume, and distance to the optical probe could not explain this paradoxical response. CONCLUSIONS: A lower HOB angle results in an increase in cortical CBF without a significant change in arterial flow velocity in AIS, but there is variability across patients in this response. Bedside CBF monitoring with diffuse correlation spectroscopy provides a potential means to individualize interventions designed to optimize CBF in AIS.
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Isquemia Encefálica/fisiopatología , Encéfalo/irrigación sanguínea , Circulación Cerebrovascular/fisiología , Accidente Cerebrovascular/fisiopatología , Anciano , Velocidad del Flujo Sanguíneo/fisiología , Encéfalo/fisiopatología , Isquemia Encefálica/diagnóstico , Isquemia Encefálica/terapia , Protocolos Clínicos , Estudios de Cohortes , Femenino , Humanos , Masculino , Persona de Mediana Edad , Monitoreo Fisiológico , Accidente Cerebrovascular/diagnóstico , Accidente Cerebrovascular/terapia , Posición Supina/fisiologíaRESUMEN
INTRODUCTION: Head-of-bed manipulation is commonly performed in the neurocritical care unit to optimize cerebral blood flow (CBF), but its effects on CBF are rarely measured. This pilot study employs a novel, non-invasive instrument combining two techniques, diffuse correlation spectroscopy (DCS) for measurement of CBF and near-infrared spectroscopy (NIRS) for measurement of cerebral oxy- and deoxy-hemoglobin concentrations, to monitor patients during head-of-bed lowering. METHODS: Ten brain-injured patients and ten control subjects were monitored continuously with DCS and NIRS while the head-of-bed was positioned first at 30° and then at 0°. Relative CBF (rCBF) and concurrent changes in oxy- (ΔHbO2), deoxy- (ΔHb), and total-hemoglobin concentrations (ΔTHC) from left/right frontal cortices were monitored for 5 min at each position. Patient and control response differences were assessed. RESULTS: rCBF, ΔHbO2, and ΔTHC responses to head lowering differed significantly between brain-injured patients and healthy controls (P < 0.02). For patients, rCBF changes were heterogeneous, with no net change observed in the group average (0.3 ± 28.2 %, P = 0.938). rCBF increased in controls (18.6 ± 9.4 %, P < 0.001). ΔHbO2, ΔHb, and ΔTHC increased with head lowering in both groups, but to a larger degree in brain-injured patients. rCBF correlated moderately with changes in cerebral perfusion pressure (R = 0.40, P < 0.001), but not intracranial pressure. CONCLUSION: DCS/NIRS detected differences in CBF and oxygenation responses of brain-injured patients versus controls during head-of-bed manipulation. This pilot study supports the feasibility of continuous bedside measurement of cerebrovascular hemodynamics with DCS/NIRS and provides the rationale for further investigation in larger cohorts.
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Lesiones Encefálicas/diagnóstico , Circulación Cerebrovascular/fisiología , Malformaciones Arteriovenosas Intracraneales/diagnóstico , Monitoreo Fisiológico/métodos , Imagen Multimodal/métodos , Hemorragia Subaracnoidea/diagnóstico , Adolescente , Adulto , Lechos , Lesiones Encefálicas/fisiopatología , Cuidados Críticos/métodos , Femenino , Tecnología de Fibra Óptica/métodos , Humanos , Malformaciones Arteriovenosas Intracraneales/fisiopatología , Presión Intracraneal/fisiología , Masculino , Persona de Mediana Edad , Proyectos Piloto , Espectroscopía Infrarroja Corta/métodos , Hemorragia Subaracnoidea/fisiopatología , Adulto JovenRESUMEN
Spreading depolarizations (SD) refer to the near-complete depolarization of neurons that is associated with brain injuries such as ischemic stroke. The present gold standard for SD monitoring in humans is invasive electrocorticography (ECoG). A promising non-invasive alternative to ECoG is diffuse optical monitoring of SD-related flow and hemoglobin transients. To investigate the clinical utility of flow and hemoglobin transients, we analyzed their association with infarction in rat focal brain ischemia. Optical images of flow, oxy-hemoglobin, and deoxy-hemoglobin were continuously acquired with Laser Speckle and Optical Intrinsic Signal imaging for 2 h after photochemically induced distal middle cerebral artery occlusion in Sprague-Dawley rats (n = 10). Imaging was performed through a 6 × 6 mm window centered 3 mm posterior and 4 mm lateral to Bregma. Rats were sacrificed after 24 h, and the brain slices were stained for assessment of infarction. We mapped the infarcted area onto the imaging data and used nine circular regions of interest (ROI) to distinguish infarcted from non-infarcted tissue. Transients propagating through each ROI were characterized with six parameters (negative, positive, and total amplitude; negative and positive slope; duration). Transients were also classified into three morphology types (positive monophasic, biphasic, negative monophasic). Flow transient morphology, positive amplitude, positive slope, and total amplitude were all strongly associated with infarction (p < 0.001). Associations with infarction were also observed for oxy-hemoglobin morphology, oxy-hemoglobin positive amplitude and slope, and deoxy-hemoglobin positive slope and duration (all p < 0.01). These results suggest that flow and hemoglobin transients accompanying SD have value for detecting infarction.
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Isquemia Encefálica , Depresión de Propagación Cortical , Oxihemoglobinas , Animales , Humanos , Ratas , Isquemia Encefálica/complicaciones , Circulación Cerebrovascular/fisiología , Depresión de Propagación Cortical/fisiología , Infarto de la Arteria Cerebral Media , Ratas Sprague-DawleyRESUMEN
The aim of this study was to investigate the effect of vagus nerve stimulation (VNS) on infarct volume and neurological recovery up to 3 weeks following transient focal cerebral ischemia. Transient ischemia was produced by filament occlusion of the proximal middle cerebral artery (MCA) in rats. The right vagus nerve was stimulated starting 30 min after MCA occlusion and consisted of 30-sec pulse trains (20 Hz) delivered to the animal's right vagus nerve every 5 min for a total period of 60 min (n = 10). All the procedures were duplicated, but no stimulus was delivered, in a control group (n = 10). Neurological evaluations were performed in all animals at 24 hr, 48 hr, 1 week, 2 weeks, and 3 weeks after MCA occlusion; animals were euthanized; and neuronal damage was evaluated in hematoxylin-eosin-stained sections. The ischemic lesion volume was smaller in the VNS-treated animals in comparison with the nonstimulated group (P < 0.02). Although the functional score in both treated and untreated groups improved over the 3-week observation period (P < 0.001), there was still a statistically significant improvement reszulting from VNS treatment compared with control animals (P < 0.05). Cerebral blood flow changes in the MCA territory during ischemia did not differ between the VNS-treated animals (31.9% ± 10.4% of baseline) and control animals (29.9% ± 9.1%; P = 0.6). Stimulation of the vagus nerve for only a brief period early in ischemia provides neuroprotection in transient ischemia, with neuroprotection persisting for at least 3 weeks.
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Circulación Cerebrovascular/fisiología , Infarto de la Arteria Cerebral Media/fisiopatología , Infarto de la Arteria Cerebral Media/terapia , Estimulación del Nervio Vago/métodos , Animales , Análisis de los Gases de la Sangre , Presión Sanguínea , Infarto Encefálico/etiología , Infarto Encefálico/prevención & control , Modelos Animales de Enfermedad , Frecuencia Cardíaca , Masculino , Examen Neurológico , Ratas , Ratas Sprague-Dawley , Factores de TiempoRESUMEN
Quantitative arterial spin labeling (ASL) estimates of cerebral blood flow (CBF) during oxygen inhalation are important in several contexts, including functional experiments calibrated with hyperoxia and studies investigating the effect of hyperoxia on regional CBF. However, ASL measurements of CBF during hyperoxia are confounded by the reduction in the longitudinal relaxation time of arterial blood (T(1a) ) from paramagnetic molecular oxygen dissolved in blood plasma. The aim of this study is to accurately quantify the effect of arbitrary levels of hyperoxia on T(1a) and correct ASL measurements of CBF during hyperoxia on a per-subject basis. To mitigate artifacts, including the inflow of fresh spins, partial voluming, pulsatility, and motion, a pulsed ASL approach was implemented for in vivo measurements of T(1a) in the rat brain at 3 Tesla. After accounting for the effect of deoxyhemoglobin dilution, the relaxivity of oxygen on blood was found to closely match phantom measurements. The results of this study suggest that the measured ASL signal changes are dominated by reductions in T(1a) for brief hyperoxic inhalation epochs, while the physiologic effects of oxygen on the vasculature account for most of the measured reduction in CBF for longer hyperoxic exposures.
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Algoritmos , Artefactos , Arterias Cerebrales/fisiopatología , Circulación Cerebrovascular , Hiperoxia/fisiopatología , Interpretación de Imagen Asistida por Computador/métodos , Angiografía por Resonancia Magnética/métodos , Animales , Arterias Cerebrales/patología , Hiperoxia/patología , Aumento de la Imagen/métodos , Masculino , Ratas , Ratas Sprague-Dawley , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Marcadores de SpinRESUMEN
Clinically, development of anti-angiogenic drugs for cancer therapy is pivotal. Longitudinal monitoring of tumour angiogenesis can help clinicians determine the effectiveness of anti-angiogenic therapy. Blood oxygen level dependent (BOLD) effect has been widely used for functional imaging and tumour oxygenation assessment. In this study, the BOLD effect is investigated under different levels of oxygen inhalation for the development of a novel angiographic MRI technique, blood oxygen level dependent angiography (BOLDangio). Under short-term (<10 min) generalized hypoxia induced by inhalation of 8% oxygen, we measure BOLD contrast as high as 25% from vessels at 9.4T using a simple gradient echo (GRE) pulse sequence. This produces high-resolution 2D and 3D maps of normal and tumour brain vasculature in less than 10 minutes. Additionally, this technique reliably detects metastatic tumours and tumour-induced intracranial hemorrhage. BOLDangio provides a sensitive research tool for MRI of vasculature under normal and pathological conditions. Thus, it may be applied as a simple monitoring technique for measuring the effectiveness of anti-angiogenic drugs in a preclinical environment.
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Angiografía/métodos , Investigación Biomédica , Neoplasias Encefálicas/irrigación sanguínea , Oxígeno/sangre , Animales , Encéfalo/metabolismo , Encéfalo/patología , Neoplasias Encefálicas/patología , Línea Celular Tumoral , Femenino , Imagen por Resonancia Magnética , Ratas , Ratas Endogámicas F344RESUMEN
Significance: Cerebral metabolic rate of oxygen ( CMRO 2 ) consumption is a key physiological variable that characterizes brain metabolism in a steady state and during functional activation. Aim: We aim to develop a minimally invasive optical technique for real-time measurement of CMRO 2 concurrently with cerebral blood flow (CBF). Approach: We used a pair of macromolecular phosphorescent probes with nonoverlapping optical spectra, which were localized in the intra- and extravascular compartments of the brain tissue, thus providing a readout of oxygen gradients between these two compartments. In parallel, we measured CBF using laser speckle contrast imaging. Results: The method enables computation and tracking of CMRO 2 during functional activation with high temporal resolution ( â¼ 7 Hz ). In contrast to other approaches, our assessment of CMRO 2 does not require measurements of CBF or hemoglobin oxygen saturation. Conclusions: The independent records of intravascular and extravascular partial pressures of oxygen, CBF, and CMRO 2 provide information about the physiological events that accompany neuronal activation, creating opportunities for dynamic quantification of brain metabolism.
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Although most functional neuroimaging studies examine task effects, interest intensifies in the "default" resting brain. Resting conditions show consistent regional activity, yet oxygen extraction fraction constancy across regions. We compared resting cerebral metabolic rates of glucose (CMRgl) measured with 18F-labeled 2-fluoro-2-deoxy-D-glucose to cerebral blood flow (CBF) 15O-H2O measures, using the same positron emission tomography scanner in 2 samples (n = 60 and 30) of healthy right-handed adults. Region to whole-brain ratios were calculated for 35 standard regions of interest, and compared between CBF and CMRgl to determine perfusion relative to metabolism. Primary visual and auditory areas showed coupling between CBF and CMRgl, limbic and subcortical regions--basal ganglia, thalamus and posterior fossa structures--were hyperperfused, whereas association cortices were hypoperfused. Hyperperfusion was higher in left than right hemisphere for most cortical and subcallosal limbic regions, but symmetric in cingulate, basal ganglia and somatomotor regions. Hyperperfused regions are perhaps those where activation is anticipated at short notice, whereas downstream cortical modulatory regions have longer "lead times" for deployment. The novel observation of systematic uncoupling of CBF and CMRgl may help elucidate the potential biological significance of the "default" resting state. Whether greater left hemispheric hyperperfusion reflects lateral dominance needs further examination.
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Química Encefálica/fisiología , Circulación Cerebrovascular/fisiología , Adolescente , Adulto , Femenino , Fluorodesoxiglucosa F18 , Humanos , Procesamiento de Imagen Asistido por Computador , Cinética , Masculino , Isótopos de Oxígeno , Radiofármacos , Adulto JovenRESUMEN
BACKGROUND: This study assesses the utility of a hybrid optical instrument for noninvasive transcranial monitoring in the neurointensive care unit. The instrument is based on diffuse correlation spectroscopy (DCS) for measurement of cerebral blood flow (CBF), and near-infrared spectroscopy (NIRS) for measurement of oxy- and deoxy-hemoglobin concentration. DCS/NIRS measurements of CBF and oxygenation from frontal lobes are compared with concurrent xenon-enhanced computed tomography (XeCT) in patients during induced blood pressure changes and carbon dioxide arterial partial pressure variation. METHODS: Seven neurocritical care patients were included in the study. Relative CBF measured by DCS (rCBF(DCS)), and changes in oxy-hemoglobin (DeltaHbO(2)), deoxy-hemoglobin (DeltaHb), and total hemoglobin concentration (DeltaTHC), measured by NIRS, were continuously monitored throughout XeCT during a baseline scan and a scan after intervention. CBF from XeCT regions-of-interest (ROIs) under the optical probes were used to calculate relative XeCT CBF (rCBF(XeCT)) and were then compared to rCBF(DCS). Spearman's rank coefficients were employed to test for associations between rCBF(DCS) and rCBF(XeCT), as well as between rCBF from both modalities and NIRS parameters. RESULTS: rCBF(DCS) and rCBF(XeCT) showed good correlation (r (s) = 0.73, P = 0.010) across the patient cohort. Moderate correlations between rCBF(DCS) and DeltaHbO(2)/DeltaTHC were also observed. Both NIRS and DCS distinguished the effects of xenon inhalation on CBF, which varied among the patients. CONCLUSIONS: DCS measurements of CBF and NIRS measurements of tissue blood oxygenation were successfully obtained in neurocritical care patients. The potential for DCS to provide continuous, noninvasive bedside monitoring for the purpose of CBF management and individualized care is demonstrated.
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Lesiones Encefálicas/diagnóstico , Lesiones Encefálicas/fisiopatología , Isquemia Encefálica/diagnóstico , Isquemia Encefálica/fisiopatología , Cuidados Críticos/métodos , Oxígeno/sangre , Espectroscopía Infrarroja Corta/métodos , Hemorragia Subaracnoidea/diagnóstico , Hemorragia Subaracnoidea/fisiopatología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Circulación Cerebrovascular/fisiología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Índice de Severidad de la Enfermedad , Adulto JovenRESUMEN
Little information exists on the role and the characteristics of perfusion changes related to periinfarct depolarization. Our aim was to visualize and monitor periinfarct flow transients (PIFTs) in Sprague-Dawley rats (n = 10) with two different laser methods in a closed-skull model of filament middle cerebral artery occlusion. A laser Doppler probe was placed over the ischemic cortex 5 mm lateral to Bregma, and a 5 x 5 mm area centered 5 mm posterior and 4 mm lateral to Bregma was thinned for laser speckle imaging. Both neurological and histological evaluations were performed at 72 hr postinjury. Mean flow during 90-min ischemia was 29% of baseline measured by laser Doppler and 36-54% by laser speckle. Flow transients occurred in all rats, the number of PIFTs being 4.6 +/- 1.8/90 min. By both methods, 95.6% of them occurred with temporal correlation. The average duration of PIFTs was also identical (162 +/- 24 and 162 +/- 34 sec, respectively). Five different morphologies of flow transients ranging from hypoperfusive to hyperemic were identified by laser speckle. The PIFTs changed their morphology dynamically over certain regions. All of the animals showed an infarct (178.5 +/- 26 mm(3)) in the middle cerebral artery territory. Laser Doppler in itself can be a reliable method for counting/detecting PIFTs, but laser speckle is capable of monitoring the dynamic changes in PIFT morphology over the penumbral and periischemic cortex.
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Encéfalo/irrigación sanguínea , Circulación Cerebrovascular , Infarto de la Arteria Cerebral Media/fisiopatología , Animales , Encéfalo/patología , Encéfalo/fisiopatología , Infarto de la Arteria Cerebral Media/patología , Flujometría por Láser-Doppler , Masculino , Microcirculación , Ratas , Ratas Sprague-Dawley , ReologíaRESUMEN
"Diffuse correlation spectroscopy" (DCS) is a technology for non-invasive transcranial measurement of cerebral blood flow (CBF) that can be hybridized with "near-infrared spectroscopy" (NIRS). Taken together these methods hold potential for monitoring hemodynamics in stroke patients. We explore the utility of DCS and NIRS to measure effects of head-of-bed (HOB) positioning at 30 degrees , 15 degrees , 0 degrees , -5 degrees and 0 degrees angles in patients with acute ischemic stroke affecting frontal cortex and in controls. HOB positioning significantly altered CBF, oxy-hemoglobin (HbO(2)) and total-hemoglobin (THC) concentrations. Moreover, the presence of an ipsilateral infarct was a significant effect for all parameters. Results are consistent with the notion of impaired CBF autoregulation in the infarcted hemisphere.
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Circulación Cerebrovascular , Técnicas de Diagnóstico Neurológico , Sistemas de Atención de Punto , Accidente Cerebrovascular/fisiopatología , Adulto , Anciano , Anciano de 80 o más Años , Estudios de Casos y Controles , Infarto Cerebral/sangre , Infarto Cerebral/fisiopatología , Femenino , Lateralidad Funcional , Hemoglobinas/metabolismo , Homeostasis , Humanos , Masculino , Persona de Mediana Edad , Fenómenos Ópticos , Oxihemoglobinas/metabolismo , Postura , Espectroscopía Infrarroja Corta/métodos , Accidente Cerebrovascular/sangreRESUMEN
alpha-Chloralose is widely used as an anesthetic in studies of the cerebrovasculature because it provides robust metabolic and hemodynamic responses to functional stimulation. However, there have been no controlled studies of focal ischemia in the rat under alpha-chloralose anesthesia. Artificially ventilated rats were prepared using 1.2-1.5% isoflurane anesthesia for filament occlusion of the right middle cerebral artery (MCA), and anesthesia was either switched to alpha-chloralose (60 mg/kg bolus, 30 mg/kg/h; n=10) or was maintained on 1% isoflurane (n=10). Following temporary MCA occlusion EEG was monitored from a screw electrode and changes in cerebral blood flow (rCBF) measured with a laser Doppler probe placed over the ischemic cortex. This study shows that alpha-chloralose is a safe anesthetic for ischemia studies and provides excellent survival. Compared with isoflurane, the cortical and total infarct volumes are larger in the alpha-chloralose-anesthetized animals, while the functional outcome at 72 h is similar. The total duration of peri-infarct flow transients (PIFTs) is also significantly longer in alpha-chloralose-anesthetized animals. The average amplitude of the flow transients showed a good correlation with the extent of edema in all animals as did the total duration of non-convulsive seizures (NCS) in the alpha-chloralose-anesthetized animals.
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Anestesia/métodos , Anestésicos Intravenosos/farmacología , Isquemia Encefálica , Circulación Cerebrovascular/efectos de los fármacos , Cloralosa/farmacología , Electroencefalografía/efectos de los fármacos , Anestesia/veterinaria , Animales , Encéfalo/irrigación sanguínea , Encéfalo/efectos de los fármacos , Lesiones Encefálicas/fisiopatología , Isquemia Encefálica/fisiopatología , Modelos Animales de Enfermedad , Infarto de la Arteria Cerebral Media , Isoflurano/farmacología , Flujometría por Láser-Doppler/veterinaria , Masculino , Ratas , Ratas Sprague-DawleyRESUMEN
The critical closing pressure ( CrCP) of the cerebral circulation depends on both tissue intracranial pressure and vasomotor tone. CrCP defines the arterial blood pressure ( ABP) at which cerebral blood flow approaches zero, and their difference ( ABP - CrCP) is an accurate estimate of cerebral perfusion pressure. Here we demonstrate a novel non-invasive technique for continuous monitoring of CrCP at the bedside. The methodology combines optical diffuse correlation spectroscopy (DCS) measurements of pulsatile cerebral blood flow in arterioles with concurrent ABP data during the cardiac cycle. Together, the two waveforms permit calculation of CrCP via the two-compartment Windkessel model for flow in the cerebral arterioles. Measurements of CrCP by optics (DCS) and transcranial Doppler ultrasound (TCD) were carried out in 18 healthy adults; they demonstrated good agreement (R = 0.66, slope = 1.14 ± 0.23) with means of 11.1 ± 5.0 and 13.0 ± 7.5 mmHg, respectively. Additionally, a potentially useful and rarely measured arteriole compliance parameter was derived from the phase difference between ABP and DCS arteriole blood flow waveforms. The measurements provide evidence that DCS signals originate predominantly from arteriole blood flow and are well suited for long-term continuous monitoring of CrCP and assessment of arteriole compliance in the clinic.
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Velocidad del Flujo Sanguíneo/fisiología , Circulación Cerebrovascular/fisiología , Presión Intracraneal/fisiología , Microvasos , Modelos Biológicos , Monitoreo Fisiológico/métodos , Adulto , Presión Sanguínea/fisiología , Traumatismos Craneocerebrales/diagnóstico por imagen , Traumatismos Craneocerebrales/fisiopatología , Voluntarios Sanos , Humanos , Microvasos/diagnóstico por imagen , Microvasos/fisiopatología , Monitoreo Fisiológico/instrumentación , Imagen Óptica , Sensibilidad y Especificidad , Análisis Espectral , Ultrasonografía Doppler TranscranealRESUMEN
BACKGROUND AND PURPOSE: Functional stimulation is accompanied by increases in regional cerebral blood flow which exceed metabolic demands under normal circumstances, but it is unknown whether functional stimulation is beneficial or detrimental in the setting of acute ischemia. The aim of this study was to determine the effect of forepaw stimulation during temporary focal ischemia on neurological and tissue outcome in a rat model of reversible focal forebrain ischemia. METHODS: Sprague-Dawley rats were prepared for temporary occlusion of the right middle cerebral artery (MCA) using the filament model. Cerebral blood flow in the MCA territory was continuously monitored with a laser-Doppler flowmeter. Subdermal electrodes were inserted into the dorsal forepaw to stimulate either the forepaw ipsilateral or contralateral to the occlusion starting 1 minute into ischemia and continuing throughout the ischemic period. A neurological evaluation was undertaken after 24 hours of reperfusion, and animals were then euthanized and brain slices stained with 2,3,5-triphenyltetrazolium chloride. Cortical and striatal damage was measured separately. RESULTS: The cortical and striatal infarct volumes were both significantly reduced in the contralateral stimulated group compared with the ipsilateral stimulated group (48% total reduction). There were no statistically significant differences in the neurobehavioral scores between the 2 groups, or in the laser-Doppler flow measurements from the MCA core. CONCLUSIONS: Functional stimulation of ischemic tissue may decrease tissue damage and improve outcome from stroke. Although the precise mechanism of this effect remains to be determined, functional stimulation could readily be translated to clinical practice.
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Isquemia Encefálica/fisiopatología , Estimulación Eléctrica , Animales , Isquemia Encefálica/diagnóstico por imagen , Isquemia Encefálica/patología , Isquemia Encefálica/terapia , Circulación Cerebrovascular , Terapia por Estimulación Eléctrica , Técnicas In Vitro , Arteria Cerebral Media/patología , Ratas , Ratas Sprague-Dawley , Ultrasonografía Doppler TranscranealRESUMEN
BACKGROUND AND PURPOSE: Activators of peroxisome proliferator-activated receptor-gamma (PPARgamma), a member of the PPAR family, increase levels of CuZn-superoxide dismutase (SOD) in cultured endothelium, suggesting a mechanism by which it may exert its protective effect within the brain. These properties raise the question of whether a PPARgamma agonist may be neuroprotective in models of ischemia without reperfusion, in which oxidative injury is less prevalent. METHODS: In 2 groups of rats, 90 minutes of middle cerebral artery (MCA) occlusion was followed by 1 day of reperfusion, with 1 group receiving pioglitazone (a PPARgamma agonist) starting 72 hours before MCA occlusion (MCAO) and continuing through the day of occlusion, whereas the other group received vehicle only. In 2 comparable groups, the MCA was occluded permanently. One day after occlusion, the animals were tested neurologically and infarct volumes were calculated. In a separate group, rats were treated with pioglitazone or vehicle for 4 days. Tissue was obtained from the cortex and the striatum 2 hours into reperfusion after 90 minutes of MCAO, and the tissue was examined for CuZn-SOD by Western blot. RESULTS: Results show a significant reduction in infarct size in the treated rats, with transient MCAO but not permanent MCAO. There was also an improvement in neurological score in the treated animals after transient MCAO. The level of CuZn-SOD was increased in the cortex in treated animals. CONCLUSIONS: These data, which show that a PPARgamma agonist reduces infarct size in transient but not permanent MCAO, suggest that the role of PPARgamma is specific to events occurring during reperfusion. Our data point to CuZn-SOD as the mediator of this neuroprotection.
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Isquemia Encefálica/patología , Encéfalo/patología , Endotelio/enzimología , Infarto de la Arteria Cerebral Media/metabolismo , PPAR gamma/fisiología , Superóxido Dismutasa/fisiología , Animales , Barrera Hematoencefálica , Western Blotting , Circulación Cerebrovascular , Concentración de Iones de Hidrógeno , Masculino , Estrés Oxidativo , PPAR gamma/agonistas , Pioglitazona , Presión , Ratas , Ratas Sprague-Dawley , Flujo Sanguíneo Regional , Daño por Reperfusión , Tiazolidinedionas/farmacología , Factores de TiempoRESUMEN
Most functional neuroimaging techniques rely on activation-flow coupling (AFC) to detect changes in regional brain function, but AFC responses may also be altered during pathophysiological conditions such as ischemia. To define the relationship between progressive ischemia and the AFC response, graded levels of cerebral blood flow reduction were produced using a rat compression ischemia model, and the cerebral hemodynamic response to forepaw stimulation was measured. Graded levels of cortical ischemia of the somatosensory cortex were induced in male Sprague-Dawley rats (n = 16) by compressing the intact dura with a 4-mm-diameter cylinder equipped with a laser-Doppler probe, combined with ipsilateral common carotid artery occlusion. At each level of CBF reduction, electric forepaw stimulation was conducted, and signal-averaged laser Doppler and evoked potential responses were recorded. A visible AFC response was present at all levels of CBF reduction (0-90% reduction from baseline), and the temporal characteristics of the response appeared largely preserved. However, the amplitude of the AFC response began to decline at levels of mild ischemia (10% flow reduction) and progressively decreased with further CBF reduction. The amplitude of the evoked response appeared to decrease in concert with the AFC amplitude and appeared to be equally sensitive to ischemia. AFC appears to be a sensitive marker for cerebral ischemia, and alterations in the AFC response occur at CBF reductions above the accepted thresholds for infarction. However, the AFC response is also preserved when flow is reduced below ischemic thresholds.
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Isquemia Encefálica/fisiopatología , Circulación Cerebrovascular/fisiología , Potenciales Evocados Somatosensoriales/fisiología , Corteza Somatosensorial/fisiopatología , Animales , Estenosis Carotídea/fisiopatología , Modelos Animales de Enfermedad , Flujometría por Láser-Doppler , Masculino , Estimulación Física , Presión/efectos adversos , Ratas , Ratas Sprague-Dawley , Corteza Somatosensorial/irrigación sanguíneaRESUMEN
We introduce and validate a pressure measurement paradigm that reduces extracerebral contamination from superficial tissues in optical monitoring of cerebral blood flow with diffuse correlation spectroscopy (DCS). The scheme determines subject-specific contributions of extracerebral and cerebral tissues to the DCS signal by utilizing probe pressure modulation to induce variations in extracerebral blood flow. For analysis, the head is modeled as a two-layer medium and is probed with long and short source-detector separations. Then a combination of pressure modulation and a modified Beer-Lambert law for flow enables experimenters to linearly relate differential DCS signals to cerebral and extracerebral blood flow variation without a priori anatomical information. We demonstrate the algorithm's ability to isolate cerebral blood flow during a finger-tapping task and during graded scalp ischemia in healthy adults. Finally, we adapt the pressure modulation algorithm to ameliorate extracerebral contamination in monitoring of cerebral blood oxygenation and blood volume by near-infrared spectroscopy.
RESUMEN
Cortical spreading depression (CSD) has previously been shown to induce tolerance to a subsequent episode of transient cerebral ischemia. The objective of the present study was to determine whether CSD also induces tolerance to permanent focal ischemia and, if so, whether tolerance may be mediated by alterations in cerebral blood flow (CBF). Sprague-Dawley rats were preconditioned by applying potassium chloride to one hemisphere for 2 hours, evoking 19 +/- 5 episodes of CSD (mean +/- SD, n = 19). Three days later, the middle cerebral artery (MCA) was permanently occluded using an intraluminal suture. In a subset of animals, laser Doppler blood flow (LDF) was monitored over the parietal cortex before and during the first 2 hours of MCA occlusion. Preconditioning with CSD reduced the hemispheric volume of infarction from 248 +/- 115 mm3 (n = 18) in sham-conditioned animals to 161 +/- 81 mm3 (n = 19, P< 0.02). Similarly, CSD reduced the neocortical volume of infarction from 126 +/- 82 mm3 to 60 +/- 61 mm3 (P < 0.01). Moreover, preconditioning with CSD significantly improved LDF during MCA occlusion from 21% +/- 7% (n = 9) of preischemic baseline in sham-conditioned animals to 29% +/- 9% (n = 7, P< 0.02). Preconditioning with CSD therefore preserved relative levels of CBF during focal ischemia and reduced the extent of infarction resulting from permanent MCA occlusion. To determine whether CSD may have altered preischemic baseline CBF, [14 C]iodoantipyrine was used in additional animals to measure CBF 3 days after CSD conditioning or sham conditioning. CSD, but not sham conditioning, significantly reduced baseline CBF in the ipsilateral neocortex to values 67% to 75% of those in the contralateral cortex. Therefore, CSD causes a long-lasting decrease in baseline CBF that is most likely related to a reduction in metabolic rate. A reduction in the rate of metabolism may contribute to the induction of tolerance to ischemia after preconditioning with CSD.
Asunto(s)
Adaptación Fisiológica/fisiología , Antipirina/análogos & derivados , Isquemia Encefálica/fisiopatología , Encéfalo/fisiopatología , Circulación Cerebrovascular/fisiología , Depresión de Propagación Cortical/fisiología , Animales , Antipirina/farmacocinética , Autorradiografía , Infarto Cerebral/patología , Flujometría por Láser-Doppler , Masculino , Ratas , Ratas Sprague-DawleyRESUMEN
Diffuse optical tomography (DOT) is an attractive approach for evaluating stroke physiology. It provides hemodynamic and metabolic imaging with unique potential for continuous noninvasive bedside imaging in humans. To date there have been few quantitative spatial-temporal studies of stroke pathophysiology based on diffuse optical signatures. The authors report DOT images of hemodynamic and metabolic contrasts using a rat middle cerebral artery occlusion (MCAO) stroke model. This study used a novel DOT device that concurrently obtains coregistered images of relative cerebral blood volume (rCBV), tissue-averaged hemoglobin oxygen saturation (Sto(2)), and relative cerebral blood flow (rCBF). The authors demonstrate how these hemodynamic measures can be synthesized to calculate an index of the oxygen extraction fraction (OEF) and the cerebral metabolic rate of oxygen consumption (CMRo(2)). Temporary (60-minute) MCAO was performed on five rats. Ischemic changes, averaged over the 60 minutes of occlusion, were as follows: rCBF = 0.42 +/- 0.04, rCBV = 1.02 +/- 0.04, DeltaSto(2) = -11 +/- 2%, rOEF = 1.39 +/- 0.06 and rCMRo(2) = 0.59 +/- 0.07. Although rOEF increased in response to decreased blood flow, rCMRo(2) decreased. The sensitivity of this method of DOT analysis is discussed in terms of assumptions about baseline physiology, and the diffuse optical results are compared with positron emission tomography, magnetic resonance imaging, and histology observations in the literature.