scholarly journals Neurovascular Coupling in Development and Disease: Focus on Astrocytes

2021 ◽  
Vol 9 ◽  
Author(s):  
Teresa L. Stackhouse ◽  
Anusha Mishra
Keyword(s):  
Blood Flow ◽  
Energy Demand ◽  
Neurovascular Unit ◽  
Neurovascular Coupling ◽  
Time Frame ◽  
Blood Oxygen Level Dependent ◽  
High Energy ◽  
Neural Activation ◽  
Blood Oxygen Level ◽  
Similar Time

Neurovascular coupling is a crucial mechanism that matches the high energy demand of the brain with a supply of energy substrates from the blood. Signaling within the neurovascular unit is responsible for activity-dependent changes in cerebral blood flow. The strength and reliability of neurovascular coupling form the basis of non-invasive human neuroimaging techniques, including blood oxygen level dependent (BOLD) functional magnetic resonance imaging. Interestingly, BOLD signals are negative in infants, indicating a mismatch between metabolism and blood flow upon neural activation; this response is the opposite of that observed in healthy adults where activity evokes a large oversupply of blood flow. Negative neurovascular coupling has also been observed in rodents at early postnatal stages, further implying that this is a process that matures during development. This rationale is consistent with the morphological maturation of the neurovascular unit, which occurs over a similar time frame. While neurons differentiate before birth, astrocytes differentiate postnatally in rodents and the maturation of their complex morphology during the first few weeks of life links them with synapses and the vasculature. The vascular network is also incomplete in neonates and matures in parallel with astrocytes. Here, we review the timeline of the structural maturation of the neurovascular unit with special emphasis on astrocytes and the vascular tree and what it implies for functional maturation of neurovascular coupling. We also discuss similarities between immature astrocytes during development and reactive astrocytes in disease, which are relevant to neurovascular coupling. Finally, we close by pointing out current gaps in knowledge that must be addressed to fully elucidate the mechanisms underlying neurovascular coupling maturation, with the expectation that this may also clarify astrocyte-dependent mechanisms of cerebrovascular impairment in neurodegenerative conditions in which reduced or negative neurovascular coupling is noted, such as stroke and Alzheimer’s disease.

scholarly journals Transmural distribution of metabolic abnormalities and glycolytic activity during dobutamine-induced demand ischemia

2008 ◽  
Vol 294 (6) ◽  
pp. H2680-H2686 ◽  
Author(s):  
Mohammad N. Jameel ◽  
Xiaohong Wang ◽  
Marcel H. J. Eijgelshoven ◽  
Abdul Mansoor ◽  
Jianyi Zhang
Keyword(s):  
Blood Flow ◽  
Coronary Stenosis ◽  
Energy Demand ◽  
Weight Ratio ◽  
Dry Weight ◽  
High Energy ◽  
Left Ventricular ◽  
Cardiac Work ◽  
Induced Demand ◽  
Systolic Thickening

The heterogeneity across the left ventricular wall is characterized by higher rates of oxygen consumption, systolic thickening fraction, myocardial perfusion, and lower energetic state in the subendocardial layers (ENDO). During dobutamine stimulation-induced demand ischemia, the transmural distribution of energy demand and metabolic markers of ischemia are not known. In this study, hemodynamics, transmural high-energy phosphate (HEP), 2-deoxyglucose-6-phosphate (2-DGP) levels, and myocardial blood flow (MBF) were determined under basal conditions, during dobutamine infusion (DOB: 20 μg·kg−1·min−1 iv), and during coronary stenosis + DOB + 2-deoxyglucose (2-DG) infusion. DOB increased rate pressure products (RPP) and MBF significantly without affecting the subendocardial-to-subepicardial blood flow ratio (ENDO/EPI) or HEP levels. During coronary stenosis + DOB + 2-DG infusion, RPP, ischemic zone (IZ) MBF, and ENDO/EPI decreased significantly. The IZ ratio of creatine phosphate-to-ATP decreased significantly [2.30 ± 0.14, 2.06 ± 0.13, and 2.04 ± 0.11 to 1.77 ± 0.12, 1.70 ± 0.11, and 1.72 ± 0.12 for EPI, midmyocardial (MID), and ENDO, respectively], and 2-DGP accumulated in all layers, as evidenced by the 2-DGP/PCr (0.55 ± 0.12, 0.52 ± 0.10, and 0.37 ± 0.08 for EPI, MID, and ENDO, respectively; P < 0.05, EPI > ENDO). In the IZ the wet weight-to-dry weight ratio was significantly increased compared with the normal zone (5.9 ± 0.5 vs. 4.4 ± 0.4; P < 0.05). Thus, in the stenotic perfused bed, during dobutamine-induced high cardiac work state, despite higher blood flow, the subepicardial layers showed the greater metabolic changes characterized by a shift toward higher carbohydrate metabolism, suggesting that a homeostatic response to high-cardiac work state is characterized by more glucose utilization in energy metabolism.

scholarly journals BOLD and Perfusion Response to Finger-Thumb Apposition after Acetazolamide Administration: Differential Relationship to Global Perfusion

2003 ◽  
Vol 23 (7) ◽  
pp. 829-837 ◽  
Author(s):  
Gregory G. Brown ◽  
Lisa T. Eyler Zorrilla ◽  
Bassem Georgy ◽  
Sandra S. Kindermann ◽  
Eric C. Wong ◽  
...  
Keyword(s):  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Blood Oxygen Level Dependent ◽  
Bold Response ◽  
Blood Oxygen Level ◽  
Individual Subject ◽  
Cerebrovascular Reserve ◽  
Global Cerebral Blood Flow ◽  
Hand Area ◽  
Cortical Perfusion

The authors studied the effects of altering global cerebral blood flow on both blood oxygen level–dependent (BOLD) response and perfusion response to finger-thumb apposition. A PICORE/QUIPSS II protocol was used to collect interleaved BOLD-weighted and perfusion-weighted images on eight finger-thumb apposition trials. Subjects were studied on a drug-free day and on a day when acetazolamide was administered between the second and third trials. After acetazolamide administration, resting cortical perfusion increased an average of 20% from preadministration levels, whereas the BOLD response to finger-thumb apposition decreased by an average of 35% in the S1M1 hand area. Contrary to predictions from the exhausted cerebrovascular reserve hypothesis and the oxygen limitation model, an effect of acetazolamide on cerebral blood flow response in the S1M1 hand area was not observed. Across the acetazolamide trials, BOLD response was inversely correlated with resting cortical perfusion for individual subject data. These results suggest that resting perfusion affects the magnitude of the BOLD response and is thus an important confounding factor in fMRI studies, and that the physiologic systems that increase cerebral blood flow in response to acetazolamide administration and systems that increase cerebral blood flow in response to altered neural activity appear to have additive effects.

scholarly journals Peritubular Capillary Oxygen Consumption in Sepsis-Induced AKI: Multi-Parametric Photoacoustic Microscopy

Nephron ◽  
2020 ◽  
Vol 144 (12) ◽  
pp. 621-625
Author(s):  
Nabin Poudel ◽  
Shuqiu Zheng ◽  
Colleen M. Schinderle ◽  
Naidi Sun ◽  
Song Hu ◽  
...  
Keyword(s):  
Blood Flow ◽  
Oxygen Consumption ◽  
Energy Demand ◽  
Oxygen Metabolism ◽  
High Energy ◽  
Renal Hemodynamics ◽  
Metabolic Reprogramming ◽  
Acoustic Microscopy ◽  
Physiological Status ◽  
Outer Medulla

Understanding and measuring parameters responsible for the pathogenesis of sepsis-induced AKI (SI-AKI) is critical in developing therapies. Blood flow to the kidney is heterogeneous, partly due to the existence of dynamic networks of capillaries in various regions, responding differentially to oxygen demand in cortex versus medulla. High energy demand regions, especially the outer medulla, are susceptible to hypoxia and subject to damage during SI-AKI. Proximal tubule epithelial cells in the cortex and the outer medulla can also undergo metabolic reprogramming during SI-AKI to maintain basal physiological status and to avoid potential damage. Current data on the assessment of renal hemodynamics and oxygen metabolism during sepsis is limited. Preclinical and clinical studies show changes in renal hemodynamics associated with SI-AKI, and in clinical settings, interventions to manage renal hemodynamics seem to help improve disease outcomes in some cases. Lack of proper tools to assess temporospatial changes in peritubular blood flow and tissue oxygen metabolism is a barrier to our ability to understand microcirculatory dynamics and oxygen consumption and their role in the pathogenesis of SI-AKI. Current tools to assess renal oxygenation are limited in their usability as these cannot perform continuous simultaneous measurement of renal hemodynamics and oxygen metabolism. Multi-parametric photo-acoustic microscopy (PAM) is a new tool that can measure real-time changes in microhemodynamics and oxygen metabolism. Use of multi-parametric PAM in combination with advanced intravital imaging techniques has the potential to understand the contribution of microhemodynamic and tissue oxygenation alterations to SI-AKI.

scholarly journals Renal Medullary Oxygenation decreases with Lower Body Negative Pressure in Healthy Young Adults

2020 ◽  
Author(s):  
Danielle Jin-Kwang Kim ◽  
Rachel C. Drew ◽  
Christopher T. Sica ◽  
Qing X. Yang ◽  
Amanda J. Miller ◽  
...  
Keyword(s):  
Blood Flow ◽  
Renal Blood Flow ◽  
Negative Pressure ◽  
Lower Body Negative Pressure ◽  
Kidney Diseases ◽  
Blood Oxygen Level Dependent ◽  
Lower Body ◽  
Sympathetic Activation ◽  
Blood Oxygen Level ◽  
Bold Mri

One in three Americans suffer from kidney diseases such as chronic kidney disease, and one of the etiologies is suggested to be the long-term renal hypoxia. Interestingly, sympathetic nervous system activation evokes a renal vasoconstrictor effect that may limit oxygen delivery to the kidney. In this report, we sought to determine if sympathetic activation evoked by lower body negative pressure (LBNP) would decrease cortical and medullary oxygenation in humans. LBNP was activated in a graded fashion (LBNP; -10, -20, and -30 mmHg), as renal oxygenation was measured (T2*, Blood Oxygen Level Dependent, BOLD MRI; n = 8). At a separate time, renal blood flow velocity (RBV) to the kidney was measured (n = 13) as LBNP was instituted. LBNP significantly reduced RBV (P = 0.041) at -30 mmHg of LBNP (Δ-8.17 ± 3.75 cm/s). Moreover, both renal medullary and cortical T2* were reduced with the graded LBNP application (main effect for the level of LBNP P = 0.0008). During recovery, RBV rapidly returned to baseline, whereas medullary T2* remained depressed into the first min of the recovery. In conclusion, sympathetic activation reduces renal blood flow and leads to a significant decrease in oxygenation in the renal cortex and medulla.

Inefficient cerebral recruitment as a vulnerability marker for schizophrenia

2012 ◽  
Vol 43 (1) ◽  
pp. 169-182 ◽  
Author(s):  
E. B. Liddle ◽  
A. T. Bates ◽  
D. Das ◽  
T. P. White ◽  
M. J. Groom ◽  
...  
Keyword(s):  
Frontal Cortex ◽  
Reaction Times ◽  
Blood Oxygen Level Dependent ◽  
Medial Frontal Cortex ◽  
Auditory Target ◽  
Neural Activation ◽  
Healthy Controls ◽  
Blood Oxygen Level ◽  
Brain Areas ◽  
Bold Responses

BackgroundPatients with schizophrenia and their first-degree relatives exhibit both abnormally diminished and increased neural activation during cognitive tasks. In particular, excessive task-related activity is often observed when tasks are easy, suggesting that inefficient cerebral recruitment may be a marker of vulnerability for schizophrenia. This hypothesis might best be tested using a very easy task, thus avoiding confounding by individual differences in task difficulty.MethodEighteen people with schizophrenia, 18 unaffected full siblings of patients with schizophrenia and 26 healthy controls performed an easy auditory target-detection task in a 3-T magnetic resonance imaging (MRI) scanner. Groups were matched for accuracy on the task. Blood oxygen level-dependent (BOLD) responses to non-target stimuli in participants with vulnerability for schizophrenia (siblings and patients) were compared with those of healthy controls, and those of patients with those of unaffected siblings. BOLD responses to targets were compared with baseline, across groups.ResultsSubjects with vulnerability for schizophrenia showed significant hyperactivation to non-targets in brain areas activated by targets in all groups, in addition to reduced deactivation to non-targets in areas suppressed by targets in all groups. Siblings showed greater activation than patients to non-targets in the medial frontal cortex. Patients exhibited significantly longer reaction times (RTs) than unaffected siblings and healthy controls.ConclusionsInefficient cerebral recruitment is a vulnerability marker for schizophrenia, marked by reduced suppression of brain areas normally deactivated in response to task stimuli, and increased activation of areas normally activated in response to task stimuli. Moreover, siblings show additional activation in the medial frontal cortex that may be protective.

scholarly journals Interictal cortical hyperresponsiveness in migraine is directly related to the presence of aura

Cephalalgia ◽  
2013 ◽  
Vol 33 (6) ◽  
pp. 365-374 ◽  
Author(s):  
Ritobrato Datta ◽  
Geoffrey K Aguirre ◽  
Siyuan Hu ◽  
John A Detre ◽  
Brett Cucchiara
Keyword(s):  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Visual Stimulus ◽  
Visual Stimulation ◽  
Blood Oxygen Level Dependent ◽  
Blood Oxygen Level ◽  
Visual Discomfort ◽  
Bold Fmri ◽  
Control Subjects ◽  
And Control

Objective The objective of this study was to compare the interictal cortical response to a visual stimulus between migraine with aura (MWA), migraine without aura (MwoA), and control subjects. Methods In a prospective case-control study, blood oxygen level-dependent functional magnetic resonance imaging (BOLD fMRI) was used to assess the response to a visual stimulus and arterial spin labeled perfusion MR to determine resting cerebral blood flow. A standardized questionnaire was used to assess interictal visual discomfort. Results Seventy-five subjects (25 MWA, 25 MwoA, and 25 controls) were studied. BOLD fMRI response to visual stimulation within primary visual cortex was greater in MWA (3.09 ± 0.15%) compared to MwoA (2.36 ± 0.13%, p = 0.0008) and control subjects (2.47 ± 0.11%, p = 0.002); responses were also greater in the lateral geniculate nuclei in MWA. No difference was found between MwoA and control groups. Whole brain analysis showed that increased activation in MWA was confined to the occipital pole. Regional resting cerebral blood flow did not differ between groups. MWA and MwoA subjects had significantly greater levels of interictal visual discomfort compared to controls ( p = 0.008 and p = 0.005, respectively), but this did not correlate with BOLD response. Conclusions Despite similar interictal symptoms of visual discomfort, only MWA subjects have cortical hyperresponsiveness to visual stimulus, suggesting a direct connection between cortical hyperresponsiveness and aura itself.

scholarly journals Insights Into Cerebral Tissue-Specific Response to Respiratory Challenges at 7T: Evidence for Combined Blood Flow and CO2-Mediated Effects

2021 ◽  
Vol 12 ◽  
Author(s):  
Allen A. Champagne ◽  
Alex A. Bhogal
Keyword(s):  
Blood Flow ◽  
Arrival Time ◽  
Vascular Diseases ◽  
Response Speed ◽  
Blood Oxygen Level Dependent ◽  
Cerebrovascular Reactivity ◽  
Specific Response ◽  
Vascular Networks ◽  
Blood Oxygen Level ◽  
Arterial Transit Time

Cerebrovascular reactivity (CVR) mapping is finding increasing clinical applications as a non-invasive probe for vascular health. Further analysis extracting temporal delay information from the CVR response provide additional insight that reflect arterial transit time, blood redistribution, and vascular response speed. Untangling these factors can help better understand the (patho)physiology and improve diagnosis/prognosis associated with vascular impairments. Here, we use hypercapnic (HC) and hyperoxic (HO) challenges to gather insight about factors driving temporal delays between gray-matter (GM) and white-matter (WM). Blood Oxygen Level Dependent (BOLD) datasets were acquired at 7T in nine healthy subjects throughout BLOCK- and RAMP-HC paradigms. In a subset of seven participants, a combined HC+HO block, referred as the “BOOST” protocol, was also acquired. Tissue-based differences in Rapid Interpolation at Progressive Time Delays (RIPTiDe) were compared across stimulus to explore dynamic (BLOCK-HC) versus progressive (RAMP-HC) changes in CO2, as well as the effect of bolus arrival time on CVR delays (BLOCK-HC versus BOOST). While GM delays were similar between the BLOCK- (21.80 ± 10.17 s) and RAMP-HC (24.29 ± 14.64 s), longer WM lag times were observed during the RAMP-HC (42.66 ± 17.79 s), compared to the BLOCK-HC (34.15 ± 10.72 s), suggesting that the progressive stimulus may predispose WM vasculature to longer delays due to the smaller arterial content of CO2 delivered to WM tissues, which in turn, decreases intravascular CO2 gradients modulating CO2 diffusion into WM tissues. This was supported by a maintained ∼10 s offset in GM (11.66 ± 9.54 s) versus WM (21.40 ± 11.17 s) BOOST-delays with respect to the BLOCK-HC, suggesting that the vasoactive effect of CO2 remains constant and that shortening of BOOST delays was be driven by blood arrival reflected through the non-vasodilatory HO contrast. These findings support that differences in temporal and magnitude aspects of CVR between vascular networks reflect a component of CO2 sensitivity, in addition to redistribution and steal blood flow effects. Moreover, these results emphasize that the addition of a BOOST paradigm may provide clinical insights into whether vascular diseases causing changes in CVR do so by way of severe blood flow redistribution effects, alterations in vascular properties associated with CO2 diffusion, or changes in blood arrival time.

scholarly journals A Model of the Dynamic Relationship between Blood Flow and Volume Changes during Brain Activation

2004 ◽  
Vol 24 (12) ◽  
pp. 1382-1392 ◽  
Author(s):  
Yazhuo Kong ◽  
Ying Zheng ◽  
David Johnston ◽  
John Martindale ◽  
Myles Jones ◽  
...  
Keyword(s):  
Blood Flow ◽  
Cerebral Blood Volume ◽  
Temporal Dynamics ◽  
Blood Oxygen Level Dependent ◽  
Extended Model ◽  
Biophysical Modeling ◽  
Blood Oxygen Level ◽  
Windkessel Model ◽  
Dynamic Relationship ◽  
Dependent Signal

The temporal relationship between changes in cerebral blood flow (CBF) and cerebral blood volume (CBV) is important in the biophysical modeling and interpretation of the hemodynamic response to activation, particularly in the context of magnetic resonance imaging and the blood oxygen level–dependent signal. Grubb et al. (1974) measured the steady state relationship between changes in CBV and CBF after hypercapnic challenge. The relationship CBVαCBFΦ has been used extensively in the literature. Two similar models, the Balloon ( Buxton et al., 1998 ) and the Windkessel ( Mandeville et al., 1999 ), have been proposed to describe the temporal dynamics of changes in CBV with respect to changes in CBF. In this study, a dynamic model extending the Windkessel model by incorporating delayed compliance is presented. The extended model is better able to capture the dynamics of CBV changes after changes in CBF, particularly in the return-to-baseline stages of the response.

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