The effect of hyperglycemia on neurovascular coupling and cerebrovascular patterning in zebrafish.
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ABSTRACT:
SUBMITTER: Chhabria K
PROVIDER: S-EPMC6985997 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:To date, the majority of neurovascular coupling studies focused on the thalamic afferents' activity in layer IV and the corresponding large spiking activity as responsible for functional hyperemia. This paper highlights the role of the secondary and late cortico-cortical transmission in neurovascular coupling. Simultaneous scalp electroencephalography (EEG) and diffuse optical imaging (DOI) measurements were obtained during multiple conditions of event-related electrical forepaw stimulation in 33 male Sprague-Dawley rats divided into 6 groups depending on the maintaining anesthetic - alpha-chloralose, pentobarbital, ketamine-xylazine, fentanyl-droperidol, isoflurane, or propofol. The somatosensory evoked potentials (SEP) were decomposed into four components and the question of which best predicts the hemodynamic responses was investigated. Results of the linear regression analysis show that the hemodynamic response is best correlated with the secondary and late cortico-cortical transmissions and not with the initial thalamic input activity in layer IV. Baseline cerebral blood flow (CBF) interacts with neural activity and influences the evoked hemodynamic responses. Finally, neurovascular coupling appears to be the same across all anesthetics used.
| S-EPMC2879067 | biostudies-literature
Project description:A numerical model of neurovascular coupling (NVC) is presented based on neuronal activity coupled to vasodilation/contraction models via the astrocytic mediated perivascular K(+) and the smooth muscle cell (SMC) Ca(2+) pathway termed a neurovascular unit (NVU). Luminal agonists acting on P2Y receptors on the endothelial cell (EC) surface provide a flux of inositol trisphosphate (IP3) into the endothelial cytosol. This concentration of IP3 is transported via gap junctions between EC and SMC providing a source of sarcoplasmic derived Ca(2+) in the SMC. The model is able to relate a neuronal input signal to the corresponding vessel reaction (contraction or dilation). A tissue slice consisting of blocks, each of which contain an NVU is connected to a space filling H-tree, simulating a perfusing arterial tree (vasculature) The model couples the NVUs to the vascular tree via a stretch mediated Ca(2+) channel on both the EC and SMC. The SMC is induced to oscillate by increasing an agonist flux in the EC and hence increased IP3 induced Ca(2+) from the SMC stores with the resulting calcium-induced calcium release (CICR) oscillation inhibiting NVC thereby relating blood flow to vessel contraction and dilation following neuronal activation. The coupling between the vasculature and the set of NVUs is relatively weak for the case with agonist induced where only the Ca(2+) in cells inside the activated area becomes oscillatory however, the radii of vessels both inside and outside the activated area oscillate (albeit small for those outside). In addition the oscillation profile differs between coupled and decoupled states with the time required to refill the cytosol with decreasing Ca(2+) and increasing frequency with coupling. The solution algorithm is shown to have excellent weak and strong scaling. Results have been generated for tissue slices containing up to 4096 blocks.
| S-EPMC4569750 | biostudies-literature
Project description:BACKGROUND AND PURPOSE: Hyperglycemia can lead to an increased rate of apoptosis of microglial cells and to damaged neurons. The relation between hyperglycemia and cerebrovascular markers on MRI is unknown. Our aim was to study the association between intraoperative hyperglycemia and cerebrovascular markers. METHODS: In this further analysis of a subgroup investigation of the BIOCOG study, 65 older non-demented patients (median 72 years) were studied who underwent elective surgery of ≥ 60 minutes. Intraoperative blood glucose maximum was determined retrospectively in each patient. In these patients, preoperatively and at 3 months follow-up a MRI scan was performed and white matter hyperintensity (WMH) volume and shape, infarcts, and perfusion parameters were determined. Multivariable logistic regression analyses were performed to determine associations between preoperative cerebrovascular markers and occurrence of intraoperative hyperglycemia. Linear regression analyses were performed to assess the relation between intraoperative hyperglycemia and pre- to postoperative changes in WMH volume. Associations between intraoperative hyperglycemia and postoperative WMH volume at 3 months follow-up were also assessed by linear regression analyses. RESULTS: Eighteen patients showed intraoperative hyperglycemia (glucose maximum ≥ 150 mg/dL). A preoperative more smooth shape of periventricular and confluent WMH was related to the occurrence of intraoperative hyperglycemia [convexity: OR 33.318 (95 % CI (1.002 - 1107.950); p = 0.050]. Other preoperative cerebrovascular markers were not related to the occurrence of intraoperative hyperglycemia. Intraoperative hyperglycemia showed no relation with pre- to postoperative changes in WMH volume nor with postoperative WMH volume at 3 months follow-up. CONCLUSIONS: We found that a preoperative more smooth shape of periventricular and confluent WMH was related to the occurrence of intraoperative hyperglycemia. These findings may suggest that a similar underlying mechanism leads to a certain pattern of vascular brain abnormalities and an increased risk of hyperglycemia.
| S-EPMC7893564 | biostudies-literature
Project description:BackgroundAltered cerebral blood flow (CBF) and amplitude of low-frequency fluctuation (ALFF) have been reported in hemodialysis patients. However, neurovascular coupling impairments, which provide a novel insight into the human brain, have not been reported in hemodialysis patients.MethodsWe combined arterial spin labeling (ASL) and blood oxygen level dependent (BOLD) techniques to investigate neurovascular coupling alterations and its relationships with demographic and clinical data in 46 hemodialysis patients and 47 healthy controls. To explore regional neuronal activity, ALFF was obtained from resting-state functional MRI. To measure cerebral vascular response, CBF was calculated from ASL. The across-voxel CBF-ALFF correlations for global neurovascular coupling and CBF/ALFF ratio for regional neurovascular coupling were compared between hemodialysis patients and healthy controls. Two-sample t-tests were used to compare the intergroup differences in CBF and ALFF. Multiple comparisons were corrected using a voxel-wise false discovery rate (FDR) method (P < 0.05).ResultsAll hemodialysis patients and healthy controls showed significant across-voxel correlations between CBF and ALFF. Hemodialysis patients showed a significantly reduced global CBF-ALFF coupling (P = 0.0011) compared to healthy controls at the voxel-level. Of note, decreased CBF/ALFF ratio was exclusively located in the bilateral amygdala involved in emotional regulation and cognitive processing in hemodialysis patients. In hemodialysis patients, the decreased CBF (right olfactory cortex, anterior cingulate gyrus and bilateral insula) and ALFF (bilateral precuneus and superior frontal gyrus) were mainly located in the default mode network and salience network-related regions as well as increased CBF in the bilateral thalamus.ConclusionsThese novel findings reveal that disrupted neurovascular coupling may be a potential neural mechanism in hemodialysis patients.
| S-EPMC7166048 | biostudies-literature
Project description:OBJECTIVE:We previously showed that MELAS patients have decreased cerebrovascular reactivity (CVR) (p? 0.002) and increased cerebral blood flow (CBF) (p<0.0026); changes correlated with disease severity and % mutant mtDNA (inversely for CVR; directly for CBF). We ran a prospective pilot in 3 MELAS sibs (m.3243A>G tRNALeu(UUR)) with variable % mutant blood mtDNA to assess effects of L-Arginine (L-Arg) (single dose and 6-wk steady-state trial) on regional CBF, arterial CVR and neurovascular coupling. METHODS:Patients were studied with 3T MRI using arterial spin labeling (ASL) to measure CBF and changes in % Blood Oxygen Level Dependent (BOLD) signal to changes in arterial partial pressure of CO2 to measure CVR. Task fMRI consisted of an alternating black and white checkerboard to evaluate visual cortex response in MELAS and controls. RESULTS:Following L-Arg, there was restoration of serum Arg (76-230 ?M) in MELAS sibs and a trend towards increasing CVR in frontal and corresponding decrease in occipital cortex; CVR was unchanged globally. There was a 29-37% reduction in baseline CBF in one patient following 6 wks of L-Arg. Pre-treatment fMRI activation in response to visual cortex stimulus was markedly decreased in the same patient compared to controls in primary visual striate cortex V1 and extrastriate regions V2 to V5 with a marked increase toward control values following a single dose and 6 wks of L-Arg. CONCLUSION:Proposed "healing" effect may be due to more efficient utilization of energy substrates with increased cellular energy balances and ensuing reduction in signalling pathways that augment flow in the untreated state. CLASSIFICATION OF EVIDENCE:This prospective pilot study provides Class III evidence that oral L-Arginine (100 mg/kg single dose or 100 mg/kg three times daily po X 6 weeks) normalizes resting blood flow from elevated pre-treatment levels in patients with MELAS syndrome, selectively increases their CVR from reduced pre-treatment levels in regions most impaired at the expense of less abnormal regions, and normalizes reduced BOLD fMRI activation in response to visual cortex stimulus. CLINICAL TRIALS.GOV (NIH):NCT01603446.
| S-EPMC7470264 | biostudies-literature
Project description:The coupling of cerebral blood flow (CBF) to neuronal activity is well preserved during evolution. Upon changes in the neuronal activity, an incompletely understood coupling mechanism regulates diameter changes of supplying blood vessels, which adjust CBF within seconds. The physiologic brain tissue oxygen content would sustain unimpeded brain function for only 1 second if continuous oxygen supply would suddenly stop. This suggests that the CBF response has evolved to balance oxygen supply and demand. Surprisingly, CBF increases surpass the accompanying increases of cerebral metabolic rate of oxygen (CMRO2). However, a disproportionate CBF increase may be required to increase the concentration gradient from capillary to tissue that drives oxygen delivery. However, the brain tissue oxygen content is not zero, and tissue pO2 decreases could serve to increase oxygen delivery without a CBF increase. Experimental evidence suggests that CMRO2 can increase with constant CBF within limits and decreases of baseline CBF were observed with constant CMRO2. This conflicting evidence may be viewed as an oxygen paradox of neurovascular coupling. As a possible solution for this paradox, we hypothesize that the CBF response has evolved to safeguard brain function in situations of moderate pathophysiological interference with oxygen supply.
| S-EPMC3887356 | biostudies-other
Project description:The C-X-C motif ligand 14 (CXCL14) is a recently discovered chemokine that is highly conserved in vertebrates and expressed in various embryonic and adult tissues. CXCL14 signaling has been implicated to function as an antiangiogenic and anticancer agent in adults. However, its function during development is unknown. We previously identified novel expression of CXCL14 mRNA in various ocular tissues during development. Here, we show that CXCL14 protein is expressed in the anterior eye at a critical time during neurovascular development and in the retina during neurogenesis. We report that RCAS-mediated knockdown of CXCL14 causes severe neural defects in the eye including precocious and excessive innervation of the cornea and iris. Absence of CXCL14 results in the malformation of the neural retina and misprojection of the retinal ganglion neurons. The ocular neural defects may be due to loss of CXCL12 modulation since recombinant CXCL14 diminishes CXCL12-induced axon growth in vitro. Furthermore, we show that knockdown of CXCL14 causes neovascularization of the cornea. Altogether, our results show for the first time that CXCL14 plays a critical role in modulating neurogenesis and inhibiting ectopic vascularization of the cornea during ocular development.
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Project description:Perturbations in cerebral blood flow and abnormalities in blood vessel structure are the hallmarks of cerebrovascular disease. While there are many genetic and environmental factors that affect these entities through a heterogeneous group of disease processes, the ultimate final pathologic insult in humans is defined as a stroke, or damage to brain parenchyma. In the case of ischemic stroke, blood fails to reach its target destination whereas in hemorrhagic stroke, extravasation of blood occurs outside of the blood vessel lumen, resulting in direct damage to brain parenchyma. As these acute events can be neurologically devastating, if not fatal, development of novel therapeutics are urgently needed. The zebrafish (Danio rerio) is an attractive model for the study of cerebrovascular disease because of its morphological and physiological similarity to human cerebral vasculature, its ability to be genetically manipulated, and its fecundity allowing for large-scale, phenotype-based screens.
| S-EPMC3982096 | biostudies-literature
Project description:Proper brain function depends on neurovascular coupling: neural activity rapidly increases local blood flow to meet moment-to-moment changes in regional brain energy demand1. Neurovascular coupling is the basis for functional brain imaging2, and impaired neurovascular coupling is implicated in neurodegeneration1. The underlying molecular and cellular mechanisms of neurovascular coupling remain poorly understood. The conventional view is that neurons or astrocytes release vasodilatory factors that act directly on smooth muscle cells (SMCs) to induce arterial dilation and increase local blood flow1. Here, using two-photon microscopy to image neural activity and vascular dynamics simultaneously in the barrel cortex of awake mice under whisker stimulation, we found that arteriolar endothelial cells (aECs) have an active role in mediating neurovascular coupling. We found that aECs, unlike other vascular segments of endothelial cells in the central nervous system, have abundant caveolae. Acute genetic perturbations that eliminated caveolae in aECs, but not in neighbouring SMCs, impaired neurovascular coupling. Notably, caveolae function in aECs is independent of the endothelial NO synthase (eNOS)-mediated NO pathway. Ablation of both caveolae and eNOS completely abolished neurovascular coupling, whereas the single mutants exhibited partial impairment, revealing that the caveolae-mediated pathway in aECs is a major contributor to neurovascular coupling. Our findings indicate that vasodilation is largely mediated by endothelial cells that actively relay signals from the central nervous system to SMCs via a caveolae-dependent pathway.
| S-EPMC7060132 | biostudies-literature
Project description:Standard practices for quantifying neurovascular coupling (NVC) with transcranial Doppler ultrasound (TCD) require participants to complete one-to-ten repetitive trials. However, limited empirical evidence exists regarding how the number of trials completed influences the validity and reliability of temporally derived NVC metrics. Secondary analyses was performed on 60 young healthy participants (30 females/30 males) who completed eight cyclical eyes-closed (20-seconds), eyes-open (40-seconds) NVC trials, using the "Where's Waldo?" visual paradigm. TCD data was obtained in posterior and middle cerebral arteries (PCA and MCA, respectively). The within-day (n = 11) and between-day (n = 17) reliability were assessed at seven- and three-time points, respectively. Repeat testing from the reliability aims were also used for the concurrent validity analysis (n = 160). PCA metrics (i.e., baseline, peak, percent increase, and area-under-the-curve) demonstrated five trials produced excellent intraclass correlation coefficient (ICC) 95% confidence intervals for validity and within-day reliability (>0.900), whereas between-day reliability was good-to-excellent (>0.750). Likewise, 95% confidence intervals for coefficient of variation (CoV) measures ranged from acceptable (<20%) to excellent (<5%) with five-or-more trials. Employing fewer than five trials produced poor/unacceptable ICC and CoV metrics. Future NVC, TCD-based research should therefore have participants complete a minimum of five trials when quantifying the NVC response with TCD via a "Where's Waldo?" paradigm.
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