scholarly journals Increased Cerebral Blood Flow after single dose of antipsychotics in healthy volunteers depends on dopamine D2 receptor density profiles

2018 ◽  
Author(s):  
Pierluigi Selvaggi ◽  
Peter C.T. Hawkins ◽  
Ottavia Dipasquale ◽  
Gaia Rizzo ◽  
Alessandro Bertolino ◽  
...  
Keyword(s):  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Single Dose ◽  
Healthy Volunteers ◽  
Mrna Expression ◽  
D2 Receptor ◽  
Controlled Study ◽  
Binding Potential ◽  
Expression Data ◽  
Spatial Coupling

AbstractAs a result of neuro-vascular coupling, the functional effects of antipsychotics in human brain have been investigated in both healthy and clinical populations using haemodynamic markers such as regional Cerebral Blood Flow (rCBF). However, the relationship between observed haemodynamic effects and the pharmacological action of these drugs has not been fully established. Here, we analysed MRI-based rCBF data from a placebo-controlled study in healthy volunteers, who received a single dose of three different D2 receptor antagonists and tested the association of the main effects of the drugs on rCBF against normative population maps of D2R protein density and gene-expression data. In particular, we correlated CBF changes after antipsychotic administration with non-displaceable binding potential (BPND) template maps of the high affinity D2-antagonist Positron Emission Tomography (PET) ligand [18F]Fallypride and brain post-mortem microarray mRNA expression data for the DRD2 gene. For all antipsychotics, rCBF changes were directly proportional to brain D2R densities and DRD2 mRNA expression measures, although PET BPND spatial profiles explained more variance as compared with mRNA profiles (PET R2 range= 0.20-0.60, mRNA PET R2 range 0.04-0.20, pairwise-comparisons all p<0.05). In addition, the spatial coupling between ΔCBF and D2R profiles varied between the different antipsychotics tested, possibly reflecting differential affinities. Overall, these results indicate that the functional effects of antipsychotics as measured with rCBF are tightly correlated with the distribution of their target receptors in striatal and extra-striatal regions. Our results further demonstrate the link between neurotransmitter targets and haemodynamic changes reinforcing rCBF as a robust in-vivo marker of drug effects. This work is important in bridging the gap between pharmacokinetic and pharmacodynamics of novel and existing compounds.

scholarly journals Increased cerebral blood flow after single dose of antipsychotics in healthy volunteers depends on dopamine D2 receptor density profiles

NeuroImage ◽  
2019 ◽  
Vol 188 ◽  
pp. 774-784 ◽  
Author(s):  
Pierluigi Selvaggi ◽  
Peter C.T. Hawkins ◽  
Ottavia Dipasquale ◽  
Gaia Rizzo ◽  
Alessandro Bertolino ◽  
...  
Keyword(s):  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Single Dose ◽  
Healthy Volunteers ◽  
Dopamine D2 Receptor ◽  
D2 Receptor ◽  
Receptor Density ◽  
Density Profiles ◽  
Dopamine D2

scholarly journals 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

Nutrients ◽  
2019 ◽  
Vol 11 (12) ◽  
pp. 3022 ◽  
Author(s):  
David Kennedy ◽  
Emma Wightman ◽  
Julie Khan ◽  
Torsten Grothe ◽  
Philippa Jackson
Keyword(s):  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Single Dose ◽  
Frontal Cortex ◽  
Task Performance ◽  
Performance Measure ◽  
Controlled Study ◽  
Double Blind ◽  
Zanthoxylum Armatum ◽  
Healthy Humans

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 h 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 h 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.

Effect of resolution recovery using graph plots on regional cerebral blood flow in healthy volunteers

2017 ◽  
Vol 31 (7) ◽  
pp. 553-562
Author(s):  
Nobuhiro Yada ◽  
Hideo Onishi ◽  
Masahiro Miyai ◽  
Kentarou Ozasa ◽  
Takashi Katsube ◽  
...  
Keyword(s):  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Healthy Volunteers ◽  
Regional Cerebral Blood Flow ◽  
Regional Cerebral Blood ◽  
Resolution Recovery

scholarly journals Cerebral blood flow autoregulation in ischemic heart failure

2017 ◽  
Vol 312 (1) ◽  
pp. R108-R113 ◽  
Author(s):  
J. R. Caldas ◽  
R. B. Panerai ◽  
V. J. Haunton ◽  
J. P. Almeida ◽  
G. S. R. Ferreira ◽  
...  
Keyword(s):  
Heart Failure ◽  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Healthy Volunteers ◽  
Neurological Complications ◽  
Ischemic Heart ◽  
Step Response ◽  
Ischemic Heart Failure ◽  
Arterial Blood ◽  
End Tidal

Patients with ischemic heart failure (iHF) have a high risk of neurological complications such as cognitive impairment and stroke. We hypothesized that iHF patients have a higher incidence of impaired dynamic cerebral autoregulation (dCA). Adult patients with iHF and healthy volunteers were included. Cerebral blood flow velocity (CBFV, transcranial Doppler, middle cerebral artery), end-tidal CO2 (capnography), and arterial blood pressure (Finometer) were continuously recorded supine for 5 min at rest. Autoregulation index (ARI) was estimated from the CBFV step response derived by transfer function analysis using standard template curves. Fifty-two iHF patients and 54 age-, gender-, and BP-matched healthy volunteers were studied. Echocardiogram ejection fraction was 40 (20–45) % in iHF group. iHF patients compared with control subjects had reduced end-tidal CO2 (34.1 ± 3.7 vs. 38.3 ± 4.0 mmHg, P < 0.001) and lower ARI values (5.1 ± 1.6 vs. 5.9 ± 1.0, P = 0.012). ARI <4, suggestive of impaired CA, was more common in iHF patients (28.8 vs. 7.4%, P = 0.004). These results confirm that iHF patients are more likely to have impaired dCA compared with age-matched controls. The relationship between impaired dCA and neurological complications in iHF patients deserves further investigation.

Changes in SPECT Cerebral Blood Flow Following Japanese Style, Superficial Acupuncture at LI-4 and LI-11 in Healthy Volunteers

2011 ◽  
Vol 17 (4) ◽  
pp. 357-362 ◽  
Author(s):  
Woo-Sang Jung ◽  
Seong-Uk Park ◽  
Jung-Mi Park ◽  
Deog-Yoon Kim ◽  
Il-Ki Hong ◽  
...  
Keyword(s):  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Healthy Volunteers

Surfactant Therapy and Intracranial Hemorrhage: Review of the Literature and Results of New Analyses

PEDIATRICS ◽  
1993 ◽  
Vol 92 (6) ◽  
pp. 775-786
Author(s):  
J. Harry Gunkel ◽  
Phillip L.C. Banks
Keyword(s):  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Birth Weight ◽  
Intracranial Hemorrhage ◽  
Incidence Rates ◽  
Surfactant Therapy ◽  
Controlled Study ◽  
Hemodynamic Changes ◽  
Increased Risk ◽  
Risk Of Hemorrhage

Background and objective. Surfactant replacement is a powerful therapy for newborns with respiratory distress syndrome, but limited observations suggest that alterations of cerebral blood flow can accompany the use of several available surfactants. An early European multicenter controlled study with beractant demonstrated an increased rate of intracranial hemorrhage in treated patients. Nine additional controlled studies were subsequently performed and included follow-up evaluations through 2 years adjusted age. This clinical experience provided a database of approximately 1700 infants to examine retrospectively for any relationship between surfactant therapy and intracranial hemorrhage. Methods. Cumulative incidence rates, hazard ratios, and 95% confidence intervals for intracranial hemorrhage were computed for each study and for appropriately pooled studies of similar design. Where an association between surfactant and the risk of intracranial hemorrhage was found, additional analyses were performed to attempt to identify intermediate physiologic events that might link administration of surfactant to the occurrence of intracranial hemorrhage. These analyses were guided by literature reports of hemodynamic changes observed in association with surfactant therapy. Results. During the controlled studies with beractant, treated newborns of 600 to 750 g birth weight were at higher risk for grades I and II intracranial hemorrhage than control newborns. There was no increased risk for grades III and IV hemorrhage among these newborns, nor was there increased risk of hemorrhage among any other patient groups. This finding did not result in increased morbidity for the affected patients; at 2 years adjusted age, they were not different from the control infants of 600 to 750 g birth weight. Retrospective examination of the database could not pinpoint the mechanism behind the finding, but it might have been related to changes in cerebral blood flow after surfactant uncompensated by ventilator management of oxygenation and ventilation. Conclusion. Surfactant therapy may set in motion hemodynamic changes that could predispose to intracranial hemorrhage in certain circumstances, but this can probably be compensated by careful management of oxygenation and ventilation. A relationship between surfactant therapy and intracranial hemorrhage is probably not isolated to any particular surfactant preparation or method of delivery; studies comparing surfactants have shown no differences in rates of intracranial hemorrhage.

Effect of labetalol on cerebral blood flow and middle cerebral arterial flow velocity in healthy volunteers

1991 ◽  
Vol 13 (1) ◽  
pp. 10-12 ◽  
Author(s):  
Torben Schroeder ◽  
Jens Schierbeck ◽  
Paul Howardy ◽  
Lisbet Knudsen ◽  
Philipp Skafte-Holm ◽  
...  
Keyword(s):  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Healthy Volunteers ◽  
Flow Velocity ◽  
Arterial Flow
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