Assessment of Cerebral Blood Flow by Means of Blood-Flow-Volume Measurement in the Internal Carotid Artery

Soustiel, Jean F.; Glenn, Thomas C.; Vespa, Paul; Rinsky, Brenda; Hanuscin, Christopher R.; Martin, Neil A.

doi:10.1161/01.str.0000080942.32331.39

Cited by 52 publications

(41 citation statements)

References 37 publications

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“…Volume blood flow measurements in the ICA with digital Doppler ultrasound and an angle-independent dual beam technology, as employed in the present study, accurately correlate with CBF values evaluated by the xenon-133 clearance technique (34). In fact, this Doppler method favorably compares with other modalities of brain perfusion imaging techniques (39).…”

Section: Methodssupporting

confidence: 56%

See 1 more Smart Citation

Cerebral blood flow is increased during controlled ovarian stimulation

Nevo¹,

Soustiel²,

Thaler³

2007

American Journal of Physiology-Heart and Circulatory Physiology

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Estrogen appears to enhance cerebral blood flow (CBF). An association between CBF and physiologically altered hormonal levels due to menstrual cycle, menopause, or exogenous manipulations such as ovariectomy or hormone replacement therapy has been demonstrated. The purpose of this study was to determine the association between ovarian stimulation and CBF in vivo by measuring blood flow in the internal carotid artery (ICA) after pituitary suppression and during controlled ovarian stimulation in women undergoing in vitro fertilization treatment cycles. ICA volume flows were measured by angle-independent dual-beam ultrasound Doppler in 12 women undergoing controlled ovarian stimulation. Measurements were performed after pituitary/ovarian suppression, in the late follicular phase, and at midluteal phase. Blood flow in the ICA increased by 22.2% and 32% in the late follicular and midluteal phases compared with the respective values obtained during ovarian suppression (P Ͻ 0.0005 and P Ͻ 0.0001, respectively). There was a significant correlation between increments in estrogen levels and increments in CBF when the late follicular phase was compared with the ovarian suppression period (r ϭ 0.8, P Ͻ 0.001). Mean blood flow velocity significantly increased (by 15.7% and 16.9%, respectively) and cerebral vascular resistance significantly decreased (by 17.6% and 26.5%) during the late follicular and midluteal phases compared with respective measures during ovarian suppression. There was a significant correlation between an increase in estrogen levels and a decrease in cerebral vascular resistance when the late follicular phase was compared with the ovarian suppression period (r ϭ Ϫ0.6, P Ͻ 0.05). These changes imply sex hormone-associated intracranial vasodilation leading to increased CBF during controlled ovarian stimulation.estrogen; progesterone; angle-independent Doppler; in vitro fertilization RECENT REPORTS HAVE SUGGESTED that the cerebral circulation may be affected by hormonal status. Increased cerebral blood flow (CBF) velocities were observed in the presence of high levels of estradiol (3,25). Progesterone was shown to increase peripheral blood flow in pigs (24) and to have neuroprotective properties in male rats (12). However, there is little information regarding the effect of estrogen and progesterone on CBF in human subjects.During controlled ovarian stimulation that is utilized for in vitro fertilization (IVF) treatment cycles, there is a significant increase in serum estradiol levels during the hyperstimulated follicular phase and the luteal phase (13). The source of estrogen during an IVF cycle is the hyperstimulated follicles in the follicular phase and the corpora lutea during the luteal phase. Progesterone levels start to increase after the induction of final oocyte maturation by human chorionic gonadotropin (hCG), and supraphysiological levels are encountered during the luteal phase (11). Progesterone is secreted during the luteal phase from multiple corpora lutea that develop after trigger of oocyte ma...

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Section: Methodssupporting

confidence: 56%

“…Blood (34). Values are means Ϯ 25 and 75 centiles and range; n ϭ 12, *P Ͻ 0.01, **P Ͻ 0.001, ***P Ͻ 0.0001.…”

Section: Discussionmentioning

confidence: 99%

Cerebral blood flow is increased during controlled ovarian stimulation

Nevo¹,

Soustiel²,

Thaler³

2007

American Journal of Physiology-Heart and Circulatory Physiology

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“…The common carotid blood flow was then corrected for the known fraction of common carotid blood flow, which supplies the cortex in pigs (58%) resulting in a calculated cortical blood flow (16). The cortical flow values we obtained are similar to those seen in humans (17)(18)(19) corrected for the differences in brain weight between human and pig. Carotidjugular A␤40 and A␤1-40 differences were determined twice in each animal separated by 15 min and averaged.…”

Section: Brain A␤ Production and Secretion In Vivo Is Similar To Thatsupporting

confidence: 81%

Large Quantities of Aβ Peptide Are Constitutively Released during Amyloid Precursor Protein Metabolism in Vivo and in Vitro

Moghekar¹,

Rao²,

Li³

et al. 2011

Journal of Biological Chemistry

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The metabolism of the amyloid precursor protein (APP) has been extensively investigated because its processing generates the amyloid-␤-peptide (A␤), which is a likely cause of Alzheimer disease. Much prior research has focused on APP processing using transgenic constructs and heterologous cell lines. Work to date in native neuronal cultures suggests that A␤ is produced in very large amounts. We sought to investigate APP metabolism and A␤ production simultaneously under more physiological conditions in vivo and in vitro using cultured rat cortical neurons and live pigs. We found in cultured neurons that both APP and A␤ are secreted rapidly and at extremely high rates into the extracellular space (2-4 molecules/neuron/s for A␤). Little APP is degraded outside of the pathway that leads to extracellular release. Two metabolic pools of APP are identified, one that is metabolized extremely rapidly (t1 ⁄ 2 ‫؍‬ 2.2 h), and another, surface pool, composed of both synaptic and extrasynaptic elements, that turns over very slowly. A␤ release and accumulation in the extracellular medium can be accounted for stoichiometrically by the extracellular release of ␤-cleaved forms of the APP ectodomain. Two ␣-cleavages of APP occur for every ␤-cleavage. Consistent with the results seen in cultured neurons, an extremely high rate of A␤ production and secretion from the brain was seen in juvenile pigs. In summary, our experiments show an enormous and rapid production and extracellular release of A␤ and the soluble APP ectodomain. A small, slowly metabolized, surface pool of full-length APP is also identified. Alzheimer disease (AD)2 is a progressive, neurodegenerative process characterized pathologically by accumulation of the ␤-amyloid peptide (A␤) in the form of extracellular plaques (1). On the basis of genetic, cellular, and animal studies the amyloid hypothesis postulates that increased deposition of A␤ in the brain is the primary influence in the pathogenesis of AD (2). A␤ is part of the amyloid precursor protein (APP) that is expressed ubiquitously by neuronal and non-neuronal cells (3-5). APP is a type 1 transmembrane glycoprotein that undergoes sequential site-specific proteolytic cleavages by either ␣-or ␤-secretase followed by ␥-secretase, which cleaves APP in the transmembrane domain to yield several secreted derivatives. Cleavage of APP by the ␤-secretase BACE1 releases a large fragment called sAPP␤ leaving behind a fragment that is acted upon by ␥-secretase at different sites to release several short peptides of which A␤40 and A␤42 are the major components (6). Alternatively, cleavage of APP by ␣-secretase occurs within the A␤ domain, precluding the formation of A␤ and resulting in the secretion of sAPP␣, a short peptide called p3, and a C-terminal domain, none of which are amyloidogenic.Both in vitro and in vivo evidence suggests that A␤ is secreted from cells under normal physiological conditions (3, 4, 7-9) but the absolute amount, an important consideration given its proposed roles and pharmacologic interest, has not...

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“…ICA-FVol measured with this device has good correlation with hemispheric cerebral blood flow measured using the 133 Xenon clearance technique (Soustiel et al, 2003) The FV measurements were performed on a DWL MultiDop transcranial Doppler (Compumedics DWL, Singen, Germany). CO 2 R was calculated by the following formula: CO 2 R = (DMCA-FV * 100% / baseline MCA-FV) / DpCO 2 ).…”

Section: Study Protocolmentioning

confidence: 99%

Variants of the Endothelial Nitric Oxide Gene and Cerebral Blood Flow after Severe Traumatic Brain Injury

Robertson

Gopinath

Valadka

et al. 2011

Journal of Neurotrauma

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Experimental studies suggest that nitric oxide produced by endothelial nitric oxide synthase (NOS3) plays a role in maintaining cerebral blood flow (CBF) after traumatic brain injury (TBI). The purpose of this study was to determine if common variants of the NOS3 gene contribute to hypoperfusion after severe TBI. Fifty-one patients with severe TBI were studied. Cerebral hemodynamics, including global CBF by the stable xenon computed tomography (CT) technique, internal carotid artery flow volume (ICA-FVol), and flow velocity in intracranial vessels, were measured within 12 h of injury, and at 48 h after injury. A blood sample was collected for DNA analysis, and genotyping of the following variants of the NOS3 gene was performed: -786T > C, 894G > T, and 27bp VNTR. Cerebral hemodynamics were most closely related to the -786T > C genotype. CBF averaged 57.7 -3.0 mL/100 g/min with the normal T/T genotype, 47.0 -2.5 mL/100 g/min with the T/C, and 37.3 -8.8 mL/100 g/min with the C/C genotype ( p = 0.0146). Cerebrovascular resistance followed an inverse pattern with the highest values occurring with the C/C genotype ( p = 0.0027). The lowest ICA-FVol of 124 -43 mL/min was found at 12 h post-injury in the more injured hemisphere of the patients with the C/C genotype ( p = 0.0085). The mortality rate was 20% in patients with the T/T genotype and 17% with the T/C genotype. In contrast, both of the patients with the C/C genotype were dead at 6 months post-injury ( p = 0.022). The findings in this study support the importance of NO produced by NOS3 activity in maintaining CBF after TBI, since lower CBF values were found in patients having the -786C allele. The study suggests that a patient's individual genetic makeup may contribute to the brain's response to injury and determine the patient's chances of surviving the injury. The results here will need to be studied in a larger number of patients, but could explain some of the variability in outcome that occurs following severe TBI.

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Assessment of Cerebral Blood Flow by Means of Blood-Flow-Volume Measurement in the Internal Carotid Artery

Cited by 52 publications

References 37 publications

Cerebral blood flow is increased during controlled ovarian stimulation

Cerebral blood flow is increased during controlled ovarian stimulation

Large Quantities of Aβ Peptide Are Constitutively Released during Amyloid Precursor Protein Metabolism in Vivo and in Vitro

Variants of the Endothelial Nitric Oxide Gene and Cerebral Blood Flow after Severe Traumatic Brain Injury

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