Cerebral Blood Flow Levels Research Articles

Effects of bolus injection duration on perfusion estimates in dynamic CT and dynamic susceptibility contrast MRI

Estimates of cerebral blood flow (CBF) and tissue mean transit time (MTT) have been shown to differ between dynamic CT perfusion (CTP) and dynamic susceptibility contrast MRI (DSC-MRI). This study investigates whether these discrepancies regarding CBF and MTT between CTP and DSC-MRI can be attributed to the different injection durations of these techniques. Five subjects were scanned using CTP and DSC-MRI. Region-wise estimates of CBF, MTT, and cerebral blood volume (CBV) were derived based on oscillatory index regularized singular value decomposition. A parametric model that reproduced the shape of measured time curves and characteristics of resulting perfusion parameter estimates was developed and used to simulate data with injection durations typical for CTP and DSC-MRI for a clinically relevant set of perfusion scenarios and noise levels. In simulations, estimates of CBF/MTT showed larger negative/positive bias and increasing variability for CTP when compared to DSC-MRI, especially for high CBF levels. While noise also affected estimates, at clinically relevant levels, the injection duration effect was larger. There are several methodological differences between CTP and DSC-MRI. The results of this study suggest that the injection duration is among those that can explain differences in estimates of CBF and MTT between these bolus tracking techniques.

A-131 Measuring the Effect of CPT-3 Administration on Regional Cerebral Blood Flow with Single-Photon Emission Computed Tomography (SPECT) in ADHD

Abstract Objective: The aim of this study is to investigate the effect of the administration of the Conners Continuous Performance Test (CPT-3) on cerebral blood flow (CBF) in children with ADHD. Methods: The data for this study was derived from a large - database. Participants in the ADHD group (n = 1853, Mage = 12.01) were similar to those in the healthy control group (n = 38, Mage = 11.70). All participants were assessed for cerebral blood flow levels before and after CPT-3 administration. Results: Multiple 2-by-2 ANOVAs with repeated measures were conducted with sphericity assumed. The overall effect of CPT-3 administration on CBF levels was significant in the right cingulate left and right sides of the frontal lobe left and right sides of the occipital, left and right sides of the parietal lobe, left and right sides of the subcortical region. Post hoc analysis with a Bonferroni adjustment revealed that there was a statistically significant increase in CBF levels from baseline to following CPT-3 administration in both the ADHD and control groups. The interaction between CPT-3 administration and ADHD diagnosis was not significant. The overall effect of ADHD diagnosis on CBF levels was not significant. Conclusions: All individuals had higher levels of CBF following the administration of CPT-3. Without an interaction, we can infer that ADHD diagnosis does not change the effect of CPT-3 administration on CBF levels. This is counterintuitive considering that CPT-3 is a test of sustained attention, a common challenge for children with ADHD. These findings need to be replicated.

A-130 Measuring Baseline Regional Cerebral Blood Flow with Single-Photon Emission Computed Tomography (SPECT) in ADHD

Abstract Objective: The aim of this study is to determine whether differences exist between children with ADHD and a healthy control group in cerebral blood flow (CBF) t-scores at baseline with no external stimuli. Methods: The data for this study was derived from a large de-identified single-photon emission computed tomography (SPECT) database. Inclusion criteria required all individuals to be under the age of 18 and assessed for CBF. Participants in the ADHD group (n = 1853, Mage = 12.01) included individuals with a formal ADHD diagnosis. Participants with co-morbid diagnoses were included. Participants in the control group (n = 38, Mage = 11.70) were healthy individuals with no prior mental health diagnoses. Race, gender, and age were considered covariates. An ANCOVA analysis was performed using t-scores of CBF levels. Results: The results of an univariate ANCOVA revealed no statistically significant differences between a healthy control group and an ADHD group in t-scores of CBF levels in the cerebellum, cingulum, frontal lobe, occipital lobe, parietal lobe, temporal lobe, vermis, or subcortical regions at baseline (all p-values<0.05). Conclusion(s): These findings contradict current literature, which has found decreased perfusion in adults with ADHD on the left side of the amygdala when compared to healthy controls and in children with ADHD in the orbitofrontal cortex and middle temporal gyrus. This disparity in findings may be due to gaps in current literature, which fail to control for gender, age, and/or race. Future studies should look at whether these results differ based on the specific subtype of ADHD are measured.

Qinzhi Zhudan formula improves memory and alleviates neuroinflammation in vascular dementia rats partly by inhibiting the TNFR1-mediated TNF pathway

The Qinzhi Zhudan formula (QZZD) exhibits a prominent therapeutic effect in the treatment of vascular dementia (VaD). This study combined a network pharmacology approach and experimental validation to identify the underlying biological mechanism of QZZD against VaD. Male Wistar rats received bilateral common carotid artery occlusion (BCCAO) surgery, and after 4 weeks of intragastric administration of QZZD, the therapeutic effect was assessed using the Morris water maze test and cerebral blood flow (CBF) assessment. Hematoxylin and eosin staining, Nissl staining, and electron microscopy were used to measure the histopathological changes in the neurons of rats. The effect of QZZD treatment on hippocampal neurotransmitters was assessed by high-performance liquid chromatography with electrochemical detection and liquid chromatography mass spectrometry. Immunofluorescence was used to observe VaD-induced microglia activation. The inflammatory cytokine levels were assessed by enzyme linked immunosorbent assay. Western blot was used to examine the TNFR1-mediated TNF pathway, which was screened out by network pharmacology analysis. QZZD treatment alleviated pathological changes and neuronal damage in VaD rats and attenuated their cognitive impairment. In addition, QZZD increased CBF and the expression of acetylcholine and 5-hydroxytryptamine in the hippocampal region. Notably, QZZD inhibited microglial activation and the expression of IL-6 and TNF-α. Network pharmacology and western blot indicated that QZZD inhibited the levels of TNFR1, NF-κBp65, p-ERK, TNF-α, and IL-6, which are related to the TNFR1-mediated TNF signaling pathway. QZZD clearly improved learning and memory function, reduced brain pathological damage, elevated CBF and hippocampal neurotransmitter levels, and alleviated neuroinflammation of VaD rats partly by inhibiting the TNFR1-mediated TNF pathway, indicating its potential value in the clinical therapy of VaD.

Painless Gastrointestinal Endoscopy Assisted with Computed Tomography Image Information Data Monitoring in Postoperative Neurocognitive Dysfunction in Patients with Combined Anesthesia of Propofol and Butorphanol Tartrate under Electronic Health.

The aim of this study was to explore the value of computed tomography (CT) images based on electronic health (E-health) combined with painless gastrointestinal endoscopy (PGE) in the diagnosis of neurocognitive function in patients with combined anesthesia of propofol and butorphanol tartrate. 126 patients undergoing PGE were selected as the research objects, and all were performed with CT perfusion imaging before and after anesthesia to obtain the cerebral blood volume (CBV), cerebral blood flow (CBF), mean transit time (MTT), and time to peak (TTP). The Montreal Cognitive Assessment (MoCA) was adopted to evaluate the cognitive function of patients. The results showed that after anesthesia, the levels of CBF and CBV in the left and right thalami, frontal lobe, and temporal lobe of the patients were lower than those before anesthesia, while TTP and MTT were higher than those before anesthesia (P < 0.05). The MoCA score after anesthesia was lower than that before anesthesia (P < 0.05). After anesthesia, the CBF, CBV, TTP, and MTT values of the left and right frontal lobes and left and right temporal lobes were significantly positively correlated with MoCA (P < 0.05). In conclusion, the brain CT image parameters based on E-health can clearly display the blood perfusion in the lesion area of the patient, which was beneficial to the PGE-assisted judgment of cognitive dysfunction in patients with propofol tartrate and butorphanol tartrate anesthesia. Therefore, CT-assisted PGE examination based on E-health had a certain clinical value in evaluating the neurocognitive function of patients.

Looking for “fNIRS Signature” in Autism Spectrum: A Systematic Review Starting From Preschoolers

Accumulating evidence suggests that functional Near-Infrared Spectroscopy (fNIRS) can provide an essential bridge between our current understanding of neural circuit organization and cortical activity in the developing brain. Indeed, fNIRS allows studying brain functions through the measurement of neurovascular coupling that links neural activity to subsequent changes in cerebral blood flow and hemoglobin oxygenation levels. While the literature offers a multitude of fNIRS applications to typical development, only recently this tool has been extended to the study of neurodevelopmental disorders (NDDs). The exponential rise of scientific publications on this topic during the last years reflects the interest to identify a “fNIRS signature” as a biomarker of high translational value to support both early clinical diagnosis and treatment outcome. The purpose of this systematic review is to describe the updating clinical applications of fNIRS in NDDs, with a specific focus on preschool population. Starting from this rationale, a systematic search was conducted for relevant studies in different scientific databases (Pubmed, Scopus, and Web of Science) resulting in 13 published articles. In these studies, fNIRS was applied in individuals with Autism Spectrum Disorder (ASD) or infants at high risk of developing ASD. Both functional connectivity in resting-state conditions and task-evoked brain activation using multiple experimental paradigms were used in the selected investigations, suggesting that fNIRS might be considered a promising method for identifying early quantitative biomarkers in the autism field.

Obesity and Cerebral Blood Flow in the Reward Circuitry of Youth With Bipolar Disorder.

BackgroundBipolar disorder (BD) is associated with elevated body mass index (BMI) and increased rates of obesity. Obesity among individuals with BD is associated with more severe course of illness. Motivated by previous research on BD and BMI in youth as well as brain findings in the reward circuit, the current study investigates differences in cerebral blood flow (CBF) in youth BD with and without comorbid overweight/obesity (OW/OB).MethodsParticipants consisted of youth, ages 13–20 years, including BD with OW/OB (BDOW/OB; n = 25), BD with normal weight (BDNW; n = 55), and normal-weight healthy controls (HC; n = 61). High-resolution T1-weighted and pseudo-continuous arterial spin labeling images were acquired using 3 Tesla magnetic resonance imaging. CBF differences were assessed using both region of interest and whole-brain voxel-wise approaches.ResultsVoxel-wise analysis revealed significantly higher CBF in reward-associated regions in the BDNW group relative to the HC and BDOW/OB groups. CBF did not differ between the HC and BDOW/OB groups. There were no significant region of interest findings.ConclusionsThe current study identified distinct CBF levels relating to BMI in BD in the reward circuit, which may relate to underlying differences in cerebral metabolism, compensatory effects, and/or BD severity. Future neuroimaging studies are warranted to examine for changes in the CBF-OW/OB link over time and in relation to treatment.

Sex Differences in Cerebral Blood Flow and Serum Inflammatory Cytokines and Their Relationships in Mild Traumatic Brain Injury.

This study aimed to investigate sex differences in cerebral blood flow (CBF) and serum inflammatory cytokines, as well as their correlations in patients with acute-stage mild traumatic brain injury (mTBI). Forty-one patients with mTBI and 23 matched healthy controls underwent 3D-pseudo-continuous arterial spin labeling imaging on 3T magnetic resonance imaging. The patients underwent cognitive evaluations and measurement of a panel of ten serum cytokines: interleukin (IL)-1I, IL-4, IL-6, IL-8, IL-10, IL-12, C–C motif chemokine ligand 2, interferon-gamma, nerve growth factor-beta (β-NGF), and tumor necrosis factor-alpha (TNF-α). Spearman rank correlation analysis was performed to evaluate the relationship between inflammation levels and CBF. We found that both male and female patients showed increased IL-1L and IL-6 levels. Female patients also demonstrated overexpression of IL-8 and low expression of IL-4. As for CBF levels, three brain regions [the right superior frontal gyrus (SFG_R), left putamen, and right precuneus] increased in male patients while three brain regions [the right superior temporal gyrus (STG_R), left middle occipital gyrus, and right postcentral (PoCG_R)] decreased in female patients. Furthermore, the STG_R in female controls was positively correlated with β-NGF while the right PoCG_R in female patients was negatively correlated with IL-8. In addition, compared with male patients, female patients showed decreased CBF in the right pallidum, which was negatively correlated with IL-8. These findings revealed abnormal expression of serum inflammatory cytokines and CBF levels post-mTBI. Females may be more sensitive to inflammatory and CBF changes and thus more likely to get cognitive impairment. This may suggest the need to pay closer attention to the female mTBI group.

Prehospital Traumatic Brain Injury Management Clinical Pearls and Pathophysiology.

Traumatic brain injury (TBI) management is complex. The brain is a sensitive, high-maintenance organ that loses its ability to take care of itself upon injury, and our primary mission is to achieve and maintain optimal levels of cerebral blood flow (CBF) from the moment of injury until recovery. The authors provide a case and discuss prehospital patient management, including adequate oxygen saturation and blood pressure, early recognition of TBI, frequent exams, detailed charting and hand-off, and fast transport to the next echelon of care.

Interrelation of cognitive functions and neural networks with blood flow velocity through the internal jugular vein in patients with chronic cerebral ischemia

Understanding age-related and functional changes in cerebral venous circulation is critical for the development of new preventive, diagnostic and therapeutic approaches to maintaining brain health in the elderly. Chronic cerebral ischemia is one of the widespread socially significant vascular diseases caused by a decrease in the level of blood circulation. To assess the role of venous outflow through the internal jugular veins in cognitive decline and neural networks in patients with chronic cerebral ischemia, 30 men and 40 women (average age 66.5 years), cognitive functions and organization of neural networks were studied at high and low levels of cerebral venous blood flow through the internal jugular veins. To assess the venous outflow, the systolic blood flow rate was measured by the internal jugular veins. A higher rate of venous outflow through internal jugular veins is associated with a more successful performance of the Luria test for verbal memory. A higher or lower blood flow rate affects the formation of neural networks of the brain. At a higher blood flow rate, the predominant areas of the resting neural networks (the passive mode network of the brain and the salient network) are localized in the frontal regions, at a low blood flow rate, the predominant neural network (frontal-parietal) is located in the left hemisphere. The state of faster and slower venous outflow forms neural networks using different neural formations that affect verbal memory. Reorganization of neural networks in this case, apparently, is the central mechanism responsible for cognitive decline in chronic cerebral ischemia (2 figs, 1 table, bibliography: 10 refs)

The relationship between blood‐brain barrier permeability and cerebral blood flow in cognitive impairment

AbstractBackgroundThe contribution of cerebral microvascular dysfunction to early cognitive impairment and dementia is increasingly recognized. Here we investigated cerebral blood flow (CBF) and blood–brain barrier (BBB) permeability in relation to early cognitive decline in APOE3‐homozygotes (ε3/ε3) and APOE4‐carriers (ε3/ε4; ε4/ε4).MethodA total of 237 participants underwent neuropsychological evaluations, venipuncture, and magnetic resonance imaging (MRI). The global Clinical Dementia Rating (CDR) was used to classify participants in cognitively unimpaired (CU, CDR=0) and mild cognitive impairment (CDR=0.5). APOE genotyping was performed via polymerase chain reaction‐based retention fragment length polymorphism analysis on DNA extracted from buffy coat. BBB permeability and CBF were estimated from dynamic contrast‐enhanced and 3D pseudo‐continuous arterial spin labeling (pCASL) MRI data, respectively, using in‐house pipelines. After excluding APOE2‐carriers and participants with CDR&gt;0.5, 143 participants (86 females [60.1%]) were included in the analysis. (Table 1)ResultStandardized CBF levels in grey matter (GM), hippocampus (HC), and parahippocampal gyrus (PHG) were not significantly different in APOE3‐homozygotes and APOE4‐carriers, after controlling for age and sex. (Figure 1) Our results of BBB permeability in 52 CU participants (27 APOE3‐homozygotes and 25 APOE4‐carriers) confirm a significantly higher BBB permeability in the HC of APOE4‐carriers compared with APOE3‐homozygotes (p&lt;0.001), as previously reported (Montagne et al., Nature, 2020), and show no relationship between BBB permeability and CBF. (Figure 2) In a subgroup of 46 participants (21 CU APOE3‐homozygotes, 18 CU APOE4‐carriers, and 7 APOE4‐carriers with CDR=0.5) who underwent a second MRI approximately 2 years after the first MRI, we observed a significant reduction (p=0.008) of CBF in APOE4‐carriers with mild cognitive impairment, but not in CU individuals.ConclusionAPOE4 is associated with higher BBB permeability in CU participants compared with APOE3‐homozygotes, but CBF is not different between the two genotypes. In the future, longitudinal data will be collected to confirm whether BBB breakdown precedes CBF alterations and to assess their relationship with cognitive decline, amyloid‐β and tau pathology.

Analgesia Effect of Verum and Sham Acupuncture Treatments in Primary Dysmenorrhea: A MRI Pilot Study.

Acupuncture is an alternative treatment for primary dysmenorrhea (PDM). However, mechanisms by which acupuncture exerts its analgesic properties are still unclear. This study aimed to explore the cerebral blood flow (CBF) response to verum and sham acupuncture treatments, and further investigate whether pre-treatment CBF is capable of assessing symptom changes after interventions. A total of 11 PDM patients in the verum group and 12 patients in the sham group participated in this study. Pain rating index (PRI), CBF, and gonadal hormone levels were acquired before and after 8-week treatments. Both verum and sham acupuncture treatments exert its analgesic effect on PDM after intervention as PRI reduced (p < 0.05). Blood gonadal levels were not significantly different after acupuncture in both groups (all p > 0.05). In the verum group, intervention-related decreases in CBF were observed in the right dorsal anterior cingulate cortex. In the sham group, regions identified as showing reductions in CBF after acupuncture included the left ventromedial prefrontal cortex, left caudate, and left insula. Patients with higher baseline CBF in the left precuneus and right hippocampus were accompanied with worse treatment response to acupuncture intervention. Mechanisms of verum and sham acupuncture treatments are dissimilar as manifested by different brain responses.

Assessment of Functional Shunting in Patients with Sickle Cell Disease

IntroductionSilent cerebral infarcts (SCI) are common in patients with sickle cell disease (SCD) and thought to be caused by a mismatch between oxygen delivery and consumption. The mechanism underlying insufficient oxygen utilization is related to severity of anemia, and paradoxically, to the elevated cerebral blood flow (CBF) observed in SCD patients. CBF is elevated as a compensatory mechanism to maintain oxygen delivery, but high CBF levels can result in rapid transit of blood through the brain capillaries, limiting offloading of oxygen to the tissue; a process called arteriovenous shunting. One way to assess functional arteriovenous shunting is to use noncontrast perfusion MRI techniques in which we can assess the signal intensity of an endogenous blood tracer when it reaches the sagittal sinus. This venous signal (VS) reflects the amount of labeled blood that has not exchanged with the brain parenchyma. Under normal physiological conditions, the VS intensity will increase approximately proportionally with CBF as we expect only some of the water to exchange with tissue as it flows by. However, it is unknown whether functional shunting scales with CBF only, or whether other hemodynamic processes play a role in patients with SCD. We hypothesize that, under pathophysiological conditions such as in SCD patients, more labeled blood may pass unexchanged through the capillaries, which results in higher VS. In the present study, we investigated functional shunting by quantifying VS and assessed its association with hemodynamic, demographic and laboratory parameters in both pediatric and adult SCD patients, and controls. In addition, VS-CBF relationship was studied by further increasing CBF after a vasodilatory challenge.MethodsWe included 28 children (mean age 12.7 ± 2.3, 9 F) and 38 adults (mean age 32.1 ± 11.2, 14 F) with SCD (HbSS and HbS), and 10 healthy race-matched adult controls (mean age 36.4 ± 15.9, 4 F). For the CBF and VS measurements, pseudo-continuous arterial spin labelling (pCASL) data were acquired using 3T MRI. We segmented the ASL blood pool in the sagittal sinus to determine a common region of interest for each group. We used these images as masks to calculate average VS. Notably, for the comparison between children and adults the ratio between VS to gray matter CBF was used (VGR) instead of the VS, to take into account higher CBF in children. To get more insight into the oxygen utilization, oxygen extraction fraction (OEF) and cerebral metabolic rate of oxygen (CMRO 2) were calculated. In adult participants acetazolamide (ACZ) was used as a vasodilatory challenge. The hematologic laboratory parameters hemoglobin (Hb) and LDH were used as markers of anemia and hemolysis, respectively.ResultsVS as a marker of cerebral shunting was higher in both adult and pediatric patients with SCD as compared to controls (p<0.01) and increased after ACZ administration in all groups (p<0.01) (Fig. 1A). VS was significantly associated with CBF both before (R 2=0.59, p<0.001) and after ACZ administration (R 2=0.57, p<0.001) in all groups (Fig. 1B). To test the impact of demographics and hematological parameters on the presence of shunting, VS was corrected for CBF (VS CBF) and the residuals were used in multiple linear regression analysis against age, sex, blood flow velocity in the brain feeding arteries, participant groups, hydroxyurea, Hb and LDH. Cerebral shunting, reflected by VS CBF showed significant association with Hb (Fig. 1C). In addition, we added OEF, CMRO 2 and ACZ condition as additional parameters in adults and used a linear mixed model to accommodate the repeated measures dependencies. A negative association between the level of cerebral shunting (VS CBF) and CMRO 2 was found (β=-0.79, p<0.001) in all groups (Fig. 1C), and in adult patients with SCD, CMRO 2, Hb (β=-14.2 p<0.001) and LDH (β=0.13, p=0.002) were significant predictors of VS CBF.ConclusionOur results show that the VS in the sagittal sinus on ASL images can be used to assess functional arteriovenous shunting in the brain. Given its negative association with CMRO 2 in combination with the negative association with hemoglobin and positive correlation with LDH, this functional shunting seems to reflect pathophysiologic shunting related to higher disease severity. Future studies will focus on the relation between functional shunting and the prevalence of SCI, investigating its link to aberrant capillary oxygen exchange in SCD. [Display omitted] DisclosuresVaclavu: Philips Healthcare: Research Funding. Biemond: GBT: Honoraria, Research Funding, Speakers Bureau; Novo Nordisk: Honoraria; Novartis: Honoraria, Research Funding, Speakers Bureau; Celgene: Honoraria; Sanquin: Research Funding.

Regulation and Intervention of Intracranial Pressure

Intracranial pressure is the total amount of pressure exerted by the brain, blood and cerebrocinal fluid in the rigid cranial space. Compliance is an indicator of the brain's tolerance for increased ICP, when compliance is exceeded, there will be a dramatic increase in the pressure/volume curve so that ICP will increase rapidly. In the injured brain, cerebral blood flow (CBF) is regulated to supply sufficient oxygen and substrates to the brain. Certain physiological factors such as hypercarbia, acidosis and hypoxemia cause vasodilation which causes an increase in CBF, seizure activity and fever will increase the level of brain metabolism and CBF. Cerebral edema is the most common cause of non-traumatic brain injury such as central nervous system infections, metabolic and systemic encephalopathy. Vasogenic brain edema occurs due to injury to the blood-brain barrier and increased capillary permeability in the area around the injury, or to inflammation, especially in CNS infections. Medical management of elevated intracranial pressure includes sedation, cerebrospinal fluid drainage, and osmotherapy with either mannitol or hypertonic salts.

Treatment evaluation of Kami Guibi-tang on participants with amnestic mild cognitive impairment using magnetic resonance imaging on brain metabolites, gamma-aminobutyric acid, and cerebral blood flow.

PurposeTo evaluate the effectiveness of Kami Guibi‐tang (KGT) in the treatment of mild cognitive impairment (MCI) using magnetic resonance imaging (MRI) on brain metabolites, neurotransmitter, and cerebral blood flow (CBF).MethodsWe randomly allocated a total of 30 MCI patients to a KGT (N = 16) or a placebo (N = 14) group and performed MRI scans before and after 24 weeks of treatment. The participants underwent brain magnetic resonance spectroscopy and MRI scans to obtain brain metabolites using Point‐RESolved Spectroscopy (PRESS) single‐voxel spectroscopy, gamma‐aminobutyric acid (GABA) neurotransmitter using Mescher–Garwood PRESS, and CBF using pseudocontinuous arterial spin labeling sequences using a 3.0 Tesla MRI system. We analyzed metabolite and neurotransmitter levels and CBF using repeated‐measure analysis of variance to evaluate between‐subject group effect, within‐subject treatment condition effect, and interaction of group by condition (group x condition).ResultsThe GABA+/creatine (Cr) ratio values were not significantly different between the before and after treatment conditions. The glutamate complex/Cr ratio difference before and after treatment was lower in the KGT group than in the placebo group, but was not statistically significant (p = 0.077). The result of region of interest–based CBF measurement showed that CBF values were significantly lower after treatment at Cluster 2 for the KGT group (p = 0.003) and the placebo group (p = 0.011), at hippocampus for the KGT group (p = 0.004) and the placebo group (p = 0.008), and at the fusiform gyrus for the KGT group (p = 0.002). Furthermore, the absolute CBF difference before and after treatment in the fusiform gyrus was significantly lower in the KGT group than in the placebo group (p = 0.024).ConclusionsAlthough a KGT treatment of 24 weeks showed some significant impact on the level of CBF, the Korean version of the mini‐mental state examination score was not significantly different between before and after treatment conditions, indicating that there was no memory function improvement after treatment in amnestic MCI patients. Therefore, further studies should be performed with a relatively larger population and extending the duration of the KGT treatment.

A functional cerebral endothelium is necessary to protect against cognitive decline

A vascular insult occurring early in disease onset may initiate cognitive decline leading to dementia, while pharmacological and lifestyle interventions can prevent this progression. Mice with a selective, tamoxifen-inducible deletion of NF-κB essential modulator (Nemo) in brain endothelial cells were studied as a model of vascular cognitive impairment. Groups included NemoFl controls and three NemobeKO groups: One untreated, and two treated with simvastatin or exercise. Social preference and nesting were impaired in NemobeKO mice and were not countered by treatments. Cerebrovascular function was compromised in NemobeKO groups regardless of treatment, with decreased changes in sensory-evoked cerebral blood flow and total hemoglobin levels, and impaired endothelium-dependent vasodilation. NemobeKO mice had increased string vessel pathology, blood-brain barrier disruption, neuroinflammation, and reduced cortical somatostatin-containing interneurons. These alterations were reversed when endothelial function was recovered. Findings strongly suggest that damage to the cerebral endothelium can trigger pathologies associated with dementia and its functional integrity should be an effective target in future therapeutic efforts.

Neuroprotective Effects of Resveratrol in Ischemic Brain Injury

Cerebral ischemia represents the third cause of death and the first cause of disability in adults. This process results from decreasing cerebral blood flow levels as a result of the occlusion of a major cerebral artery. This restriction in blood supply generates low levels of oxygen and glucose, which leads to a decrease in the energy metabolism of the cell, producing inflammation, and finally, neurological deterioration. Currently, blood restoration of flow is the only effective approach as a therapy in terms of ischemic stroke. However, a significant number of patients still have a poor prognosis, probably owing to the increase in the generation of reactive oxygen species (ROS) during the reperfusion of damaged tissue. Oxidative stress and inflammation can be avoided by modulating mitochondrial function and have been identified as potential targets for the treatment of cerebral ischemia. In recent years, the beneficial actions of flavonoids and polyphenols against cerebrovascular diseases have been extensively investigated. The use of resveratrol (RSV) has been shown to markedly decrease brain damage caused by ischemia in numerous studies. According to in vitro and in vivo experiments, there is growing evidence that RSV is involved in several pathways, including cAMP/AMPK/SIRT1 regulation, JAK/ERK/STAT signaling pathway modulation, TLR4 signal transduction regulation, gut/brain axis modulation, GLUT3 up-regulation inhibition, neuronal autophagy activation, and de novo SUR1 expression inhibition. In this review, we summarize the recent outcomes based on the neuroprotective effect of RSV itself and RSV-loaded nanoparticles in vitro and in vivo models focusing on such mechanisms of action as well as describing the potential therapeutic strategies in which RSV plays an active role in cases of ischemic brain injury.

Stuttering: A Disorder of Energy Supply to Neurons?

Stuttering is a disorder characterized by intermittent loss of volitional control of speech movements. This hypothesis and theory article focuses on the proposal that stuttering may be related to an impairment of the energy supply to neurons. Findings from electroencephalography (EEG), brain imaging, genetics, and biochemistry are reviewed: (1) Analyses of the EEG spectra at rest have repeatedly reported reduced power in the beta band, which is compatible with indications of reduced metabolism. (2) Studies of the absolute level of regional cerebral blood flow (rCBF) show conflicting findings, with two studies reporting reduced rCBF in the frontal lobe, and two studies, based on a different method, reporting no group differences. This contradiction has not yet been resolved. (3) The pattern of reduction in the studies reporting reduced rCBF corresponds to the regional pattern of the glycolytic index (GI; Vaishnavi et al., 2010). High regional GI indicates high reliance on non-oxidative metabolism, i.e., glycolysis. (4) Variants of the gene ARNT2 have been associated with stuttering. This gene is primarily expressed in the brain, with a pattern roughly corresponding to the pattern of regional GI. A central function of the ARNT2 protein is to act as one part of a sensor system indicating low levels of oxygen in brain tissue and to activate appropriate responses, including activation of glycolysis. (5) It has been established that genes related to the functions of the lysosomes are implicated in some cases of stuttering. It is possible that these gene variants result in a reduced peak rate of energy supply to neurons. (6) Lastly, there are indications of interactions between the metabolic system and the dopamine system: for example, it is known that acute hypoxia results in an elevated tonic level of dopamine in the synapses. Will mild chronic limitations of energy supply also result in elevated levels of dopamine? The indications of such interaction effects suggest that the metabolic theory of stuttering should be explored in parallel with the exploration of the dopaminergic theory.

Effect of Advanced Glycation End Products on Cognition in Older Adults with Type 2 Diabetes: Results from a Pilot Clinical Trial

Background: Dietary advanced glycation end-products (AGEs) are linked to cognitive decline. However, clinical trials have not tested the effect of AGEs on cognition in older adults. Objective: The aim of the current pilot trial was to examine the feasibility of an intervention to reduce dietary AGEs on cognition and on cerebral blood flow (CBF). Methods: The design is a pilot randomized controlled trial of dietary AGEs reduction in older adults with type 2 diabetes. Seventy-five participants were randomized to two arms. The control arm received standard of care (SOC) guidelines for good glycemic control; the intervention arm, in addition to SOC guidelines, were instructed to reduce their dietary AGEs intake. Global cognition and CBF were assessed at baseline and after 6 months of intervention. Results: At baseline, we found a reverse association between AGEs and cognitive functioning, possibly reflecting the long-term toxicity of AGEs on the brain. There was a significant improvement in global cognition at 6 months in both the intervention and SOC groups which was more prominent in participants with mild cognitive impairment. We also found that at baseline, higher AGEs were associated with increased CBF in the left inferior parietal cortex; however, 6 months of the AGEs lowering intervention did not affect CBF levels, despite lowering AGEs exposure in blood. Conclusion: The current pilot trial focused on the feasibility and methodology of intervening through diet to reduce AGEs in older adults with type 2 diabetes. Our results suggest that participants with mild cognitive impairment may benefit from an intensive dietary intervention.

Trans-Ocular Brain Impedance Indices Predict Pressure Reactivity Index Changes in a Porcine Model of Hypotension and Cerebral Autoregulation Perturbation.

Cerebrovascular autoregulation (CA) is a protective mechanism that enables the cerebral vasculature to automodulate tone in response to changes in cerebral perfusion pressure to ensure constant levels of cerebral blood flow (CBF) and oxygen delivery. CA can be impaired after neurological injury and contributes to secondary brain injury. In this study, we report novel impedance indices using trans-ocular brain impedance (TOBI) during controlled systemic hemorrhage and hypotension to assess CA in comparison with pressure reactivity index (PRx). Yorkshire swine were instrumented to record intracranial pressure (ICP), mean arterial pressure (MAP), and CBF. TOBI was recorded using electrocardiographic electrodes placed on the closed eyelids. Impedance changes (dz) were recorded in response to introducing an alternating current (0.4mA) through the electrodes. MAP, ICP, and CBF were also measured. Animals were subjected to a controlled hemorrhage to remove 30-40% of each animal's total blood volume over 25-35min. Hemorrhage was titrated to reach an MAP of approximately 35mm Hg and end-tidal carbon dioxide above 28mm Hg. PRx was calculated as a moving Pearson correlation between MAP and ICP. TOBI indices were calculated as the amplitude of the respiratory-induced changes in dz. DZx was calculated as a moving Pearson correlation between dz and MAP. TOBI indices (dz and DZx) were compared with hemodynamic indicators and PRx. dz was shown to be highly correlated with MAP, ICP, cerebral perfusion pressure, and CBF (r = - 0.823, - 0.723, - 0.813, and - 0.726), respectively (p < 0.0001). During hemorrhage, cerebral perfusion pressure and CBF had a mean percent decrease (standard deviation) from baseline of - 54.2% (12.5%) and - 28.3% (14.7%), respectively, whereas dz increased by 277% (268%). Receiver operator characteristics and precision-recall curves demonstrated high predictive performance of DZx when compared with PRx with an area under the curve above 0.82 and 0.89 for receiver operator characteristic and precision-recall curves, respectively, with high sensitivity and positive predictive power. TOBI indices appear to track changes in PRx and hemodynamics that affect CA during hemorrhage-induced hypotension. TOBI may offer a suitable, less invasive surrogate to PRx for monitoring and assessing CA.