-
1.
Long-Term Outcomes of Cerebral Blood Flow and Neurotransmitter Receptor Function on Iodine-123-Iomazenil Single-Photon Emission Computed Tomography and Cognitive Assessments After Parent Artery Occlusion Combined with Cerebral Revascularization for Internal Carotid Artery Aneurysms.
Kubo, Y, Koji, T, Murakami, T, Yoshida, K, Matsumoto, Y, Ogasawara, K
World neurosurgery. 2020;:e199-e205
Abstract
OBJECTIVE Many studies of external-internal carotid artery (EC-IC) bypass as cerebral revascularization for unclippable internal carotid artery (ICA) aneurysms have reported surgical outcomes, including bypass patency and aneurysm resolution. However, no previous studies have assessed the long-term outcomes of cerebral blood flow (CBF), brain neural density, and cognition. The purpose of the present study was to evaluate the long-term outcomes of CBF and neurotransmitter receptor function using early and late images of iodine-123 (123I)-iomazenil (IMZ) single-photon emission computed tomography (SPECT) and the cognitive function of patients who had undergone EC-IC bypass for symptomatic aneurysms in the cavernous portion of the ICA. METHODS We performed a prospective observational study of 11 patients who had undergone superficial temporal artery-middle cerebral artery bypass or bypass using a saphenous vein graft for symptomatic aneurysms in the cavernous portion of the ICA. One patient experienced extensive infarction and, therefore, did not undergo postoperative testing. 123I-IMZ SPECT was performed with scanning at 23 minutes (early) and 180 minutes (late) after tracer administration before and after surgery. The preoperative and follow-up neuropsychological test scores from 6 patients were also analyzed. RESULTS None of 10 patients who had undergone EC-IC bypass showed reductions in CBF and brain neural density. In addition, the neuropsychological test scores had not changed significantly from preoperatively to postoperatively. CONCLUSION Using early and late 123I-IMZ SPECT, the present study has demonstrated that patients undergoing uncomplicated cerebral revascularization for unclippable ICA aneurysms will not experience reductions in CBF or neurotransmitter receptor function, and their cognitive function was not impaired.
-
2.
Opening of BKCa channels alters cerebral hemodynamic and causes headache in healthy volunteers.
Al-Karagholi, MA, Ghanizada, H, Nielsen, CAW, Skandarioon, C, Snellman, J, Lopez Lopez, C, Hansen, JM, Ashina, M
Cephalalgia : an international journal of headache. 2020;(11):1145-1154
Abstract
INTRODUCTION Preclinical data implicate large conductance calcium-activated potassium (BKCa) channels in the pathogenesis of headache and migraine, but the exact role of these channels is still unknown. Here, we investigated whether opening of BKCa channels would cause headache and vascular effects in healthy volunteers. METHODS In a randomized, double-blind, placebo-controlled, cross-over study, 21 healthy volunteers aged 18-39 years were randomly allocated to receive an intravenous infusion of 0.05 mg/min BKCa channel opener MaxiPost and placebo on two different days. The primary endpoints were the difference in incidence of headache and the difference in area under the curve (AUC) for headache intensity scores (0-12 hours) and for middle cerebral artery blood flow velocity (VMCA) (0-2 hours) between MaxiPost and placebo. The secondary endpoints were the differences in area under the curve for superficial temporal artery and radial artery diameter (0-2 hours) between MaxiPost and placebo. RESULTS Twenty participants completed the study. Eighteen participants (90%) developed headache after MaxiPost compared with six (30%) after placebo (p = 0.0005); the difference of incidence is 60% (95% confidence interval 36-84%). The area under the curve for headache intensity (AUC0-12 hours, p = 0.0003), for mean VMCA (AUC0-2 hours, p = 0.0001), for superficial temporal artery diameter (AUC0-2 hours, p = 0.003), and for radial artery diameter (AUC0-2 hours, p = 0.03) were significantly larger after MaxiPost compared to placebo. CONCLUSION MaxiPost caused headache and dilation in extra- and intracerebral arteries. Our findings suggest a possible role of BKCa channels in headache pathophysiology in humans. ClinicalTrials.gov, ID: NCT03887325.
-
3.
A Randomized, Crossover Study of the Acute Cognitive and Cerebral Blood Flow Effects of Phenolic, Nitrate and Botanical Beverages in Young, Healthy Humans.
Jackson, PA, Wightman, EL, Veasey, R, Forster, J, Khan, J, Saunders, C, Mitchell, S, Haskell-Ramsay, CF, Kennedy, DO
Nutrients. 2020;(8)
Abstract
BACKGROUND In whole foods, polyphenols exist alongside a wide array of other potentially bioactive phytochemicals. Yet, investigations of the effects of combinations of polyphenols with other phytochemicals are limited. OBJECTIVE The current study investigated the effects of combining extracts of beetroot, ginseng and sage with phenolic-rich apple, blueberry and coffee berry extracts. DESIGN This randomized, double-blind, placebo-controlled crossover design investigated three active beverages in 32 healthy adults aged 18-49 years. Each investigational beverage comprised extracts of beetroot, ginseng and sage. Each also contained a phenolic-rich extract derived from apple (containing 234 mg flavanols), blueberry (300 mg anthocyanins) or coffee berry (440 mg chlorogenic acid). Cognition, mood and CBF parameters were assessed at baseline and then again at 60, 180 and 360 min post-drink. RESULTS Robust effects on mood and CBF were seen for the apple and coffee berry beverages, with increased subjective energetic arousal and hemodynamic responses being observed. Fewer effects were seen with the blueberry extract beverage. CONCLUSIONS Either the combination of beetroot, ginseng and sage was enhanced by the synergistic addition of the apple and coffee berry extract (and to a lesser extent the blueberry extract) or the former two phenolic-rich extracts were capable of evincing the robust mood and CBF effects alone.
-
4.
Effects of milrinone on cerebral perfusion and postoperative cognitive function in spine surgery: Secondary analysis of a CONSORT-compliant randomized controlled trial.
Choi, H, Huh, J, Koo, J, Lee, J, Hwang, W
Medicine. 2020;(46):e21717
-
-
Free full text
-
Abstract
OBJECTIVE To compare the effects of milrinone, sodium nitroprusside (SNP), and nitroglycerin (NTG) on induced hypotension, cerebral perfusion, and postoperative cognitive function in elderly patients undergoing spine surgery. METHODS Sixty patients >60 years scheduled for lumbar fusion surgery were assigned to receive milrinone (group M), SNP (group S), or NTG (group N). The administration of the study drug was initiated immediately after perivertebral muscle retraction and was stopped after completion of interbody fusion. Target blood pressure was a decrease of 30% in systolic blood pressure from baseline or mean blood pressure of 60 to 65 mm Hg. The regional cerebral venous oxygen saturation (rSVO2), as a measure of cerebral perfusion, and the change in perioperative Mini-Mental State Examination (MMSE) score, as a measure of postoperative cognitive function, were assessed. RESULTS During the administration of the study drug, the overall and lowest intraoperative rSVO2 values were significantly higher (P = .01 and P = .01, respectively), and the duration of rSVO2 <60% was shorter in group M than in the other groups (P = .03). In group M, intraoperative rSVO2 was not different from the basal value, whereas in groups S and N, rSVO2 was significantly lower than the basal value during the administration of the study drug, but then returned to the basal value after terminating the study drug. Basal MMSE scores were comparable among the 3 groups. The MMSE score on postoperative day 5 was higher in group M than the other groups. CONCLUSIONS Milrinone used to induce hypotension resulted in better intraoperative cerebral perfusion and postoperative cognitive function compared to SNP and nitroglycerin.
-
5.
UBC-Nepal Expedition: Haemoconcentration underlies the reductions in cerebral blood flow observed during acclimatization to high altitude.
Howe, CA, Ainslie, PN, Tremblay, JC, Carter, HH, Patrician, A, Stembridge, M, Williams, A, Drane, AL, Delorme, E, Rieger, MG, et al
Experimental physiology. 2019;(12):1963-1972
-
-
Free full text
-
Abstract
NEW FINDINGS What is the central question of this study? The aim was to evaluate the degree to which increases in haematocrit alter cerebral blood flow and cerebral oxygen delivery during acclimatization to high altitude. What is the main finding and its importance? Through haemodilution, we determined that, after 1 week of acclimatization, the primary mechanism contributing to the cerebral blood flow response during acclimatization is an increase in haemoglobin and haematocrit. The remaining contribution to the cerebral blood flow response during acclimatization is likely to be attributable to ventilatory acclimatization. ABSTRACT At high altitude, an increase in haematocrit (Hct) is achieved through altitude-induced diuresis and erythropoiesis, both of which result in increased arterial oxygen content. Given the impact of alterations in Hct on oxygen content, haemoconcentration has been hypothesized to mediate, in part, the attenuation of the initial elevation in cerebral blood flow (CBF) at high altitude. To test this hypothesis, healthy men (n = 13) ascended to 5050 m over 9 days without the aid of prophylactic acclimatization medications. After 1 week of acclimatization at 5050 m, participants were haemodiluted by rapid saline infusion (2.10 ± 0.28 l) to return Hct towards pre-acclimatization values. Arterial blood gases, Hct, global CBF (duplex ultrasound) and haemodynamic variables were measured after initial arrival at 5050 m and after 1 week of acclimatization at high altitude, before and after the haemodilution protocol. After 1 week at 5050 m, the Hct increased from 42.5 ± 2.5 to 49.6 ± 2.5% (P < 0.001), and it was subsequently reduced to 45.6 ± 2.3% (P < 0.001) after haemodilution. Global CBF decreased from 844 ± 160 to 619 ± 136 ml min-1 (P = 0.033) after 1 week of acclimatization and increased to 714 ± 204 ml min -1 (P = 0.045) after haemodilution. Despite the significant changes in Hct, and thus oxygen content, cerebral oxygen delivery was unchanged at all time points. Furthermore, these observations occurred in the absence of any changes in mean arterial blood pressure, cardiac output, arterial blood pH or oxygen saturation pre- and posthaemodilution. These data highlight the influence of Hct in the regulation of CBF and are the first to demonstrate experimentally that haemoconcentration contributes to the reduction in CBF during acclimatization to altitude.
-
6.
The Acute and Chronic Cognitive and Cerebral Blood-Flow Effects of Nepalese Pepper (Zanthoxylum armatum DC.) Extract-A Randomized, Double-Blind, Placebo-Controlled Study in Healthy Humans.
Kennedy, D, Wightman, E, Khan, J, Grothe, T, Jackson, P
Nutrients. 2019;(12)
Abstract
Background: Zanthoxylum armatum DC. (ZA) is a traditional Asian culinary spice and medicinal compound, which is rich in monoterpenes and hydroxy α-sanshool. Mechanistic interactions with the monoamine, cholinergic and cannabinoid neurotransmission systems, as well as transient receptor potential (TRP) and potassium ion channels, may predispose ZA to modulate human brain function. Objectives: To investigate the effects of a single dose and 56-days supplementation with a lipid extract of ZA on cognitive function, mood and cerebral blood-flow (CBF) parameters in the pre-frontal cortex during cognitive task performance. Design: Double-blind, randomized, parallel groups study with N = 82 healthy males and females between the ages of 30 and 55 years. Assessments were undertaken pre-dose and at 1, 3 and 5 hours post-dose on the first (Day 1) and last (Day 56) days of supplementation. Results: A single dose of ZA (Day 1) resulted in acute improvements on a 'Speed of Attention' factor and the Rapid Visual Information Processing (RVIP) task, in comparison to placebo. However, following ZA participants were less accurate on the name-to-face recall task. After 56 days of ZA consumption (Day 56), speed was enhanced on a global 'Speed of Performance' measure, comprising data from all of the timed tasks in the computerized battery. Participants also completed more correct Serial 3s Subtractions at the 3 hours assessment and were less mentally fatigued throughout the day than participants consuming placebo. These effects were complemented on both Day 1 and Day 56 by modulation of CBF parameters, as assessed by Near Infrared Spectroscopy (NIRS). The primary finding here was a reduced hemodynamic response during the RVIP task. Conclusion: ZA improves aspects of cognitive performance, in particular the speed of performing tasks, in healthy humans and results in concomitant reductions in hemodynamic responses in the frontal cortex during task performance. The findings suggest an increase in neural efficiency following ZA.
-
7.
Misery perfusion and amyloid deposition in atherosclerotic major cerebral artery disease.
Yamauchi, H, Kagawa, S, Takahashi, M, Oishi, N, Ono, M, Higashi, T
NeuroImage. Clinical. 2019;:101762
Abstract
Although experimental studies have shown that global cerebral hypoperfusion leads to amyloid deposition in the hemisphere with carotid artery occlusion in rodents, the results of such occurrence are controversial in humans. Hence, we aim to determine whether global cerebral hypoperfusion leading to decreased blood flow relative to metabolic demand [increased oxygen extraction fraction (OEF), misery perfusion] is associated with increases in amyloid deposition in the hemisphere with atherosclerotic major cerebral artery disease in patients. We evaluated the distribution of β-amyloid plaques using positron emission tomography and a [18F]-pyridylbenzofuran derivative (18F-FPYBF-2) in 13 patients with unilateral atherosclerotic disease of the internal carotid artery (ICA) or middle cerebral artery (MCA) disease and no cortical infarction. The distribution volume ratio (DVR) of 18F- FPYBF-2 was calculated using dynamic data and Logan graphical analysis with reference tissue and was correlated with the cerebral blood flow (CBF), cerebral metabolic rate of oxygen (CMRO2), and OEF, obtained from 15O-gas PET. The mean cortical value was calculated as the mean value within the frontal, posterior cingulate, precuneus, parietal, and lateral temporal cortical regions. Significant reductions in CBF and CMRO2 and increases in OEF were found in the hemisphere ipsilateral to the arterial lesion compared with the contralateral hemisphere. There was no significant difference for 18F-FPYBF-2 DVR between hemispheres. The ipsilateral to contralateral ratio of the 18F- FPYBF-2 DVR was increased in 3 patients, while the ipsilateral to contralateral OEF ratio was increased in 4 patients. The incidence of an increased hemispheric DVR ratio was significantly higher in patients with an increased hemispheric OEF ratio (3/4) than in patients without (0/9) (p < 0.02). Although the 18F- FPYBF-2 DVR in the ipsilateral hemisphere was positively correlated with OEF after adjustment for the 18F- FPYBF-2 DVR in the contralateral hemisphere using multiple regression analysis (p < 0.05), the contribution rate of OEF was small (R2 = 5.5%). Only one of the 4 patients with an increased hemispheric OEF ratio showed amyloid positivity based on the DVR value. In atherosclerotic major cerebral artery disease, misery perfusion accompanied only small increases of amyloid deposition at best. Misery perfusion was not associated with amyloid positivity.
-
8.
Effects of Nilvadipine on Cerebral Blood Flow in Patients With Alzheimer Disease.
de Jong, DLK, de Heus, RAA, Rijpma, A, Donders, R, Olde Rikkert, MGM, Günther, M, Lawlor, BA, van Osch, MJP, Claassen, JAHR
Hypertension (Dallas, Tex. : 1979). 2019;(2):413-420
-
-
Free full text
-
Abstract
Cerebrovascular changes, including reduced cerebral blood flow (CBF), occur early in the development of Alzheimer disease and may accelerate disease progression. This randomized, double-blind, placebo-controlled study investigated how 6 months of treatment with the calcium antagonist nilvadipine would affect CBF in patients with mild-to-moderate Alzheimer disease. CBF was measured with magnetic resonance arterial spin labeling in whole-brain gray matter and in a priori defined regions of interest including the hippocampus. Fifty-eight patients were randomly assigned (29 in each group), of whom 22 in both groups had no magnetic resonance exclusion criteria and were medication compliant over 6 months. Mean age was 72.8±6.2 years, mean mini-mental state examination was 20.4±3.4. Nilvadipine treatment lowered systolic blood pressure (Δ=-11.5 [95% CI, -19.7 to -3.2] mm Hg; P<0.01), while whole-brain gray-matter CBF remained stable (Δ=5.4 [95% CI, -6.4 to 17.2] mL/100 g per minute; P=0.36). CBF in the hippocampus increased (left: Δ=24.4 [95% CI, 4.3-44.5] mL/100 g per minute; P=0.02; right: Δ=20.1 [95% CI, -0.6 to 40.8] mL/100 g per minute; P=0.06). There was no significant change in CBF in the posterior cingulate cortex (Δ=5.2 [95% CI, -16.5 to 27.0] mL/100 g per minute; P=0.63) or other regions of interest. In conclusion, nilvadipine reduced blood pressure and increased CBF in the hippocampus, whereas other regions showed stable or small nonsignificant increases in CBF. These findings not only indicate preserved cerebral autoregulation in Alzheimer disease but also point toward beneficial cerebrovascular effects of antihypertensive treatment. Clinical Trial Registration- URL: http://www.clinicaltrials.gov . Unique identifier: NCT02017340.
-
9.
Dietary nitrate supplementation enhances cerebrovascular CO2 reactivity in a sex-specific manner.
Fan, JL, O'Donnell, T, Gray, CL, Croft, K, Noakes, AK, Koch, H, Tzeng, YC
Journal of applied physiology (Bethesda, Md. : 1985). 2019;(3):760-769
Abstract
Insufficient nitric oxide (NO) bioavailability plays an important role in endothelial dysfunction, and increased NO has the potential to enhance cerebral blood flow (CBF). Dietary supplementation with sodium nitrate, a precursor of NO, could improve cerebrovascular function, but this has not been investigated. In 17 individuals, we examined the effects of a 7-day supplementation of dietary nitrate (0.1 mmol·kg-1·day -1) on cerebrovascular function using a randomized, single-blinded placebo-controlled crossover design. We hypothesized that 7-day dietary nitrate supplementation increases CBF response to CO2 (cerebrovascular CO2 reactivity) and cerebral autoregulation (CA). We assessed middle cerebral artery blood velocity (MCAv) and blood pressure (BP) at rest and during CO2 breathing. Transfer function analysis was performed on resting beat-to-beat MCAv and BP to determine CA, from which phase, gain, and coherence of the BP-MCAv data were derived. Dietary nitrate elevated plasma nitrate concentration by ~420% (P < 0.001) and lowered gain (d = 1.2, P = 0.025) and phase of the BP-MCAv signal compared with placebo treatment (d = 0.7, P = 0.043), while coherence was unaffected (P = 0.122). Dietary nitrate increased the MCAv-CO2 slope in a sex-specific manner (interaction: P = 0.016). Dietary nitrate increased the MCAv-CO2 slope in men (d = 1.0, P = 0.014 vs. placebo), but had no effect in women (P = 0.919). Our data demonstrate that dietary nitrate greatly increased cerebrovascular CO2 reactivity in healthy individuals, while its effect on CA remains unclear. The selective increase in the MCAv-CO2 slope observed in men indicates a clear sexual dimorphic role of NO in cerebrovascular function.NEW & NOTEWORTHY We found dietary nitrate supplementation improved the brain blood vessels' response to CO2, cerebrovascular CO2 reactivity, without affecting blood pressure in a group of healthy individuals. Meanwhile, the effect of dietary nitrate on the relationship between blood pressure and brain blood flow, cerebral autoregulation, was inconclusive. The improvement in cerebrovascular CO2 reactivity was only observed in the male participants, alluding to a sex difference in the effect of dietary nitrate on brain blood flow control. Our findings indicate that dietary nitrate could be an effective strategy to enhance cerebrovascular CO2 reactivity.
-
10.
Association Between Fatty Acids Profile and Cerebral Blood Flow: An Exploratory fNIRS Study on Children with and without ADHD.
Grazioli, S, Crippa, A, Mauri, M, Piazza, C, Bacchetta, A, Salandi, A, Trabattoni, S, Agostoni, C, Molteni, M, Nobile, M
Nutrients. 2019;(10)
Abstract
Polyunsaturated fatty acids (PUFAs) biostatus has been proposed as possible attention deficit hyperactivity disorder (ADHD) diagnosis biomarker. The present exploratory study aimed to investigate the association between PUFAs biostatus and cerebral cortex metabolism measured by functional Near Infrared Spectroscopy (fNIRS) in a sample of children with and without ADHD. 24 children with ADHD and 22 typically developing (TD) peers, aged 8-14, were recruited. Linoleic, arachidonic, docosahexaenoic and eicosapentaenoic acids levels were evaluated in whole blood. All children underwent fNIRS while performing an n-back working memory task. Between groups comparisons revealed lower levels of arachidonic acid in children with ADHD and stronger NIRS signal in TD participants, especially when completing more difficult tasks. Correlations conducted between fNIRS activation and PUFA biostatus revealed several associations between hemodynamic changes in the frontoparietal regions and fatty acids profile across participants. This result was also confirmed by the multiple hierarchical regression analyses that remarked an inverse effect of eicosapentaenoic acid levels on oxyhemoglobin values in right frontoparietal region. Such preliminary findings, if confirmed, would suggest that PUFAs could play a role in atypical neurodevelopment.