scholarly journals In Vivo Measurements of Brain Glucose Transport Using the Reversible Michaelis–Menten Model and Simultaneous Measurements of Cerebral Blood Flow Changes during Hypoglycemia

2001 ◽  
Vol 21 (6) ◽  
pp. 653-663 ◽  
Author(s):  
In-Young Choi ◽  
Sang-Pil Lee ◽  
Seong-Gi Kim ◽  
Rolf Gruetter
Keyword(s):  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Glucose Transport ◽  
Plasma Glucose ◽  
Glucose Concentration ◽  
Defense Mechanisms ◽  
Normal Brain ◽  
Brain Glucose ◽  
The Brain

Glucose is the major substrate that sustains normal brain function. When the brain glucose concentration approaches zero, glucose transport across the blood–brain barrier becomes rate limiting for metabolism during, for example, increased metabolic activity and hypoglycemia. Steady-state brain glucose concentrations in α-chloralose anesthetized rats were measured noninvasively as a function of plasma glucose. The relation between brain and plasma glucose was linear at 4.5 to 30 mmol/L plasma glucose, which is consistent with the reversible Michaelis–Menten model. When the model was fitted to the brain glucose measurements, the apparent Michaelis-Menten constant, Kt, was 3.3 ± 1.0 mmol/L, and the ratio of the maximal transport rate relative to CMRglc, Tmax/CMRglc, was 2.7 ± 0.1. This Kt is comparable to the authors' previous human data, suggesting that glucose transport kinetics in humans and rats are similar. Cerebral blood flow (CBF) was simultaneously assessed and constant above 2 mmol/L plasma glucose at 73 ± 6 mL 100 g−1 min−1. Extrapolation of the reversible Michaelis–Menten model to hypoglycemia correctly predicted the plasma glucose concentration (2.1 ± 0.6 mmol/L) at which brain glucose concentrations approached zero. At this point, CBF increased sharply by 57% ± 22%, suggesting that brain glucose concentration is the signal that triggers defense mechanisms aimed at improving glucose delivery to the brain during hypoglycemia.

Ex Vivo MuEtinuciear NMR Spectroscopy of Perfused, Respiring Rat Brain Slices: Model Studies of Hypoxia, Ischemia, and Excitotoxscit

1997 ◽  
Author(s):  
L. Litt ◽  
M.T. Espanol
Keyword(s):  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Nmr Spectroscopy ◽  
Clinical Care ◽  
Brain Slices ◽  
In Vivo Nmr ◽  
In Vivo Nmr Spectroscopy ◽  
Permanent Brain Damage ◽  
The Brain

We believe there are important roles for in vivo NMR spectroscopy techniques in studies of protection and treatment in stroke. Perhaps the primary utility of in vivo NMR spectroscopy is to establish the relevance of metabolic integrity, intracellular pH, and intracellular energy stores to concurrent changes occurring both at gross physiological levels (e.g., changes in cerebral blood flow, or blood oxygenation), and at microscopic or cellular levels. It has long been known that the brain is exquisitely sensitive to deprivations of oxygen, glucose, and cerebral blood flow. Routine human surgery on a limb takes place every day with tourniquets stopping all blood flow for up to two hours. In contrast, the deprivation of all blood flow to the brain (global ischemia) for approximately 5 minutes can result in severe, permanent brain damage. Research has gone on for more than 30 years to understand why the brain’s revival time is so much shorter, and to discover brain biochemical interventions that might dramatically extend the brain’s intolerance beyond 5 minutes, and therefore be relevant to protection and treatment of stroke. (Kogure and Hossmann, 1985; 1993) Stroke, defined as a permanent neurologic deficit arising from the death of brain cells, kills ∼ 150,000 people in the U.S.A. each year, and is the third leading cause of death (Feinleib et al., 1993). It is the next malady to escape, once one has dodged death from cardiovascular disease and cancer. Many, if not most, U.S.A. stroke victims will receive neurological clinical care not substantially different from what was provided 30 years ago. Most stroke patients will be put in intensive care units where blood pressure will be regulated and kept in a “safe” range, with the body given supportive care and the brain given an opportunity to heal itself. The problem of stroke is actually quite complex because there are several different kinds of stroke (ischemic, hemorrhagic, etc.), and because numerous systemic physiological factors are of relevance. Nevertheless, exciting advances in brain biochemistry suggest that stroke therapy and prophylaxis axe likely to improve dramatically in the near future (Zivin and Choi, 1991).

Blood-brain barrier permeability of 11C-labeled alcohols and 15O-labeled water

1976 ◽  
Vol 230 (2) ◽  
pp. 543-552 ◽  
Author(s):  
ME Raichle ◽  
JO Eichling ◽  
MG Straatmann ◽  
MJ Welch ◽  
KB Larson ◽  
...  
Keyword(s):  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Time Course ◽  
Brain Capillary ◽  
Permeability Characteristics ◽  
Permeability Surface ◽  
Brain Barrier Permeability ◽  
The Individual ◽  
The Brain

The extraction of 11C-labeled methanol, ethanol, and isopropanol, as well as 15O-labeled water by the brain during a single capillary transit, was studied in vivo in six adult rhesus monkeys by external detection of the time course of these tracers subsequent to their internal carotid artery injection. The data demonstrate the feasibility of accurately measuring brain permeability of highly diffusible substances by this technique and show that neither water nor the alcohols studied freely equilibrate with brain when the cerebral blood flow exceeds 30 ml/100 g min-1. At a cerebral blood flow of 50 ml/100 g min-1 only about 93% of an injected bolus of labeled water freely exchanges with brain, compared with methanol (93%), ethanol (97%), and isopropanol (99%). The brain capillary permeability-surface area (PS) products computed from these data were 0.023 cm3/s g-1 (water), 0.024 cm3/s g-1 (methanol), 0.030 cm3/s g-1 (ethanol), and 0.062 cm3/s g-1 (isopropanol). This sequence of PS products is consistent with the individual lipid solubilities of the alcohols studied and underscores the unique brain permeability characteristics of lipid-insoluble water.

scholarly journals Acid-Sensing Ion Channels

2019 ◽  
Vol 125 (10) ◽  
pp. 907-920 ◽  
Author(s):  
Frank M. Faraci ◽  
Rebecca J. Taugher ◽  
Cynthia Lynch ◽  
Rong Fan ◽  
Subhash Gupta ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Local Treatment ◽  
Brain Dysfunction ◽  
Normal Brain ◽  
Bed Nucleus ◽  
Extracellular Acidosis ◽  
Arteriolar Diameter

Rationale: Precise regulation of cerebral blood flow is critical for normal brain function. Insufficient cerebral blood flow contributes to brain dysfunction and neurodegeneration. Carbon dioxide (CO 2 ), via effects on local acidosis, is one of the most potent regulators of cerebral blood flow. Although a role for nitric oxide in intermediate signaling has been implicated, mechanisms that initiate CO 2 -induced vasodilation remain unclear. Objective: Acid-sensing ion channel-1A (ASIC1A) is a proton-gated cation channel that is activated by extracellular acidosis. Based on work that implicated ASIC1A in the amygdala and bed nucleus of the stria terminalis in CO 2 -evoked and acid-evoked behaviors, we hypothesized that ASIC1A might also mediate microvascular responses to CO 2 . Methods and Results: To test this hypothesis, we genetically and pharmacologically manipulated ASIC1A and assessed effects on CO 2 -induced dilation of cerebral arterioles in vivo. Effects of inhalation of 5% or 10% CO 2 on arteriolar diameter were greatly attenuated in mice with global deficiency in ASIC1A ( Asic1a −/− ) or by local treatment with the ASIC inhibitor, psalmotoxin. Vasodilator effects of acetylcholine, which acts via endothelial nitric oxide synthase were unaffected, suggesting a nonvascular source of nitric oxide may be key for CO 2 responses. Thus, we tested whether neurons may be the cell type through which ASIC1A influences microvessels. Using mice in which Asic1a was specifically disrupted in neurons, we found effects of CO 2 on arteriolar diameter were also attenuated. Conclusions: Together, these data are consistent with a model wherein activation of ASIC1A, particularly in neurons, is critical for CO 2 -induced nitric oxide production and vasodilation. With these findings, ASIC1A emerges as major regulator of microvascular tone.

Compartmental analysis of regional cerebral blood flow in patients with acute severe head injuries

1977 ◽  
Vol 47 (5) ◽  
pp. 699-712 ◽  
Author(s):  
Erna M. Enevoldsen ◽  
Finn Taagehøj Jensen
Keyword(s):  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Brain Tissue ◽  
Regional Cerebral Blood Flow ◽  
Head Injuries ◽  
Initial Slope ◽  
Flow Index ◽  
Normal Brain ◽  
Regional Cerebral Blood ◽  
The Brain

✓ Bicompartmental analysis for the calculation of regional cerebral blood flow (rCBF) from 133Xe clearance in brain tissue has not been thoroughly explored in clinical studies. Most authors rely either on the average rCBF obtained by height/area analysis of the clearance curves or on the initial-slope flow index. Possibly the reason is that the validity of the bimodal flow distribution in abnormal brain tissue is considered questionable. In the present study, bicompartmental analysis, performed by a least-square computerized iterative approach, was used in the calculation of the flow and weight of the tissue of the brain of patients with severe head injuries. The analysis was found to give important information of the nature and course of the brain lesions even if the clearance curves did not have the normal bi-exponential shape, provided the results obtained were properly interpreted. In such cases, the values of the flow and relative weight could not be taken as flow and weight values of gray and white matter, but rather as indices of fast and slower flow components. The interpretation of the results was based on the identification of three types of 13-minute clearance curves, each being characteristic of a type of brain lesion. The clearance curves from fairly normal brain tissue appeared to be bi-exponential; curves from areas of severe cortical contusion had, in addition, an initial and rapid “third” component, a tissue peak, whereas curves from severely edematous brain tissue approached the monoexponential shape.

scholarly journals Synthesis and evaluation of N-isopropyl-p-[11C]methylamphetamine as a novel cerebral blood flow tracer for positron emission tomography

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Jun Toyohara ◽  
Norihiro Harada ◽  
Takeharu Kakiuchi ◽  
Hiroyuki Ohba ◽  
Masakatsu Kanazawa ◽  
...  
Keyword(s):  
Positron Emission Tomography ◽  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Emission Tomography ◽  
Emission Computed Tomography ◽  
Normal Brain ◽  
Brain Uptake ◽  
Pet Tracer ◽  
Positron Emission ◽  
The Brain

Abstract Introduction Increases in fasting plasma glucose (PG) levels lead to a decrease in 2-deoxy-2-[18F]fluoro-d-glucose ([18F]FDG) uptake in the normal brain, especially in the precuneus, resulting in an Alzheimer’s disease (AD)-like uptake pattern. Therefore, patients with higher PG levels, such as those with diabetes, can be erroneously diagnosed with AD when positron emission tomography (PET) imaging is done using [18F]FDG, due to reduced uptake of [18F]FDG in the precuneus. To help avoid an erroneous diagnosis of AD due to differences in glucose metabolism, evaluating cerebral blood flow (CBF) in the brain is useful. However, current techniques such as single photon emission computed tomography (SPECT) and [15O]H2O PET have limitations regarding early diagnosis of AD because the images they produce are of low resolution. Here, we developed a novel CBF PET tracer that may be more useful than [18F]FDG for diagnosis of AD. Methods We synthesized and evaluated N-isopropyl-p-[11C]methylamphetamine ([11C]4) as a carbon-11-labeled analogue of the standard CBF SPECT tracer N-isopropyl-p-[123I]iodoamphetamine. Fundamental biological evaluations such as biodistribution, peripheral metabolism in mice, and brain kinetics of [11C]4 in non-human primates with PET with successive measurement of [15O]H2O were performed. Results [11C]4 was synthesized by methylation of the corresponding tributyltin precursor (2) with [11C]MeI in a palladium-promoted Stille cross-coupling reaction. The brain uptake of [11C]4 in mice peaked at 5–15 min after injection and then promptly decreased. Most radioactivity in the brain was detected in the unchanged form, although in the periphery, [11C]4 was rapidly metabolized to hydrophilic components. Acetazolamide (AZM) treatment significantly increased the brain uptake of [11C]4 without affecting the blood levels of radioactivity in mice. Preliminary kinetics analysis showed that the K1 of [11C]4 reflected regional CBF in a vehicle-treated monkey, but that the K1 did not reflect CBF in higher flow regions after AZM loading. Conclusion [11C]4 is a potential novel CBF PET tracer. Further validation studies are needed before [11C]4 can be used in humans.

scholarly journals Cerebral Blood Flow Regulation in Pregnancy, Hypertension, and Hypertensive Disorders of Pregnancy

2019 ◽  
Vol 9 (9) ◽  
pp. 224 ◽  
Author(s):  
Jones-Muhammad ◽  
Warrington
Keyword(s):  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Normal Pregnancy ◽  
Systemic Blood Pressure ◽  
Normal Brain ◽  
Hypertensive Disorders Of Pregnancy ◽  
Pregnancy Hypertension ◽  
Hypertensive Disorders ◽  
The Brain ◽  
In Pregnancy

The regulation of cerebral blood flow (CBF) allows for the metabolic demands of the brain to be met and for normal brain function including cognition (learning and memory). Regulation of CBF ensures relatively constant blood flow to the brain despite changes in systemic blood pressure, protecting the fragile micro-vessels from damage. CBF regulation is altered in pregnancy and is further altered by hypertension and hypertensive disorders of pregnancy including preeclampsia. The mechanisms contributing to changes in CBF in normal pregnancy, hypertension, and preeclampsia have not been fully elucidated. This review summarizes what is known about changes in CBF regulation during pregnancy, hypertension, and preeclampsia.

scholarly journals An Ultrasonic Doppler Venous Outflow Method for the Continuous Measurement of Cerebral Blood Flow in Conscious Sheep

1994 ◽  
Vol 14 (4) ◽  
pp. 680-688 ◽  
Author(s):  
Richard Upton ◽  
Cliff Grant ◽  
Guy Ludbrook
Keyword(s):  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Continuous Measurement ◽  
Venous Outflow ◽  
Sagittal Sinus ◽  
Global Cerebral Blood Flow ◽  
Conscious Sheep ◽  
End Tidal ◽  
The Brain

A pulsed ultrasonic Doppler venous outflow method was developed for the continuous measurement of global cerebral blood flow (CBF) in conscious sheep. The sheep were prepared under anesthesia with a “suture down”-style ultrasonic flow probe on the dorsal sagittal sinus placed via a trephine hole. Angiographic and dye studies showed that the dorsal sagittal sinus at the point of placement of the probe collected the majority of the blood from the cerebral hemispheres. Studies of the blood velocity profile across the sinus showed that the dimensions of the dorsal sagittal sinus changed minimally with changes in CBF in vivo. The velocity measurements were calibrated under anesthesia against an in vivo direct venous outflow method. Control CBF values for six sheep ranged from 31 to 53 ml/min for the area of brain described above; for two sheep in which the weight of the brain was determined, this gave total CBF values of approximately 34 and 30 ml min−1 100 g−1. The CBF measured varied in the expected manner with changes in the end-tidal CO2 concentration in expired breath and showed transient reductions with the barbiturate thiopentone and transient increases with the opiate alfentanil. It is concluded that the method is simple and accurate.

scholarly journals Simultaneous Determination of Regional Cerebral Blood Flow and Blood—Brain Glucose Transport Kinetics in the Gerbil

1983 ◽  
Vol 3 (2) ◽  
pp. 193-199 ◽  
Author(s):  
A. Lorris Betz ◽  
Fausto Iannotti
Keyword(s):  
Blood Flow ◽  
Cerebral Cortex ◽  
Cerebral Blood Flow ◽  
Basal Ganglia ◽  
Glucose Transport ◽  
Blood Glucose Concentration ◽  
Brain Regions ◽  
Brain Glucose ◽  
Arterial Blood ◽  
Half Saturation Constant

Cerebral blood flow (CBF) and unidirectional transport of glucose from blood to brain were measured simultaneously in four brain regions of the pentobarbital-anesthetized gerbil. The method consisted of the intravenous injection of a bolus containing [14C]butanol and [3H]glucose, followed by continuous withdrawal of arterial blood and sampling of brain 25 s later. CBF was lowest in the cerebral cortex (50 ml 100 g−1 min−1), highest in the brainstem (89 ml 100 g−1 min−1), and intermediate in the basal ganglia and cerebellum (66 and 69 ml 100 g−1 min−1, respectively). The kinetics of blood-to-brain glucose transport were measured in animals whose blood glucose concentration had been altered by glucose or insulin injections. The half-saturation constant for glucose transport ( Km) was similar in all brain regions (7.37–8.14 m M), while the maximal rate of transport ( Vmax) was lowest in the cerebral cortex (1.55 μmol g−1 min−1) and significantly higher in the basal ganglia, cerebellum, and brainstem (1.81–2.02 μmol g−1 min−1). These values for CBF and glucose transport are similar to those reported in the literature for other pentobarbital-anesthetized animals. The method provides a simple and rapid technique for determining the effect of ischemia and alterations in CBF on blood-to-brain glucose transport.

In vivo measurement of brain glucose transport and metabolism employing glucose- -11C

1975 ◽  
Vol 228 (6) ◽  
pp. 1936-1948 ◽  
Author(s):  
ME Raichle ◽  
KB Larson ◽  
ME Phelps ◽  
Grubb RL ◽  
MJ welch ◽  
...  
Keyword(s):  
Glucose Transport ◽  
Turnover Time ◽  
Glucose Turnover ◽  
Brain Glucose ◽  
Fick Principle ◽  
In Vivo Measurement ◽  
Arterial Blood ◽  
Free Glucose ◽  
The Brain

The radiopharmaceutical glucose--11C was used in vivo measurement of brain-glucose transport kinetics and metabolism in the rhesus monkey. Radiotracer was injected intravenously as a bolus. Radioactivity was continuously recorded from the head and from the arterial blood via an indwelling peripheral artery catheter for a collectionperiod of 2-3 min. To correct the reading obtained from the head for radioactivitycontained in blood, a second intravenous injection of the vascular tracer -15O-labeled carboxyhemoglobin was used. The method was tested in nine phencyclidine-anesthetized monkeys in which cerebral glucose metabolism (CMRGlc) was simultaneously measured by our method and by a standard method emplying the Fick principle. A highlysignificant correlation was found between the two methods of measuring CMRGlc (r =0.929). In addition, our model predicted a ratio of forward-to-reverse glucose flux across the blood-brain barrier (BBR) (1.37 plus or minus 0.23 SD), the brain-to-bloodglucose concentration ratio across the BBB (0.633 plus or minus 0.14), the relative tissue free-glucose space (17 plus or minus 7%), the brain free-glucose concentration (13.6plus or minus 8.5 mg/100 g of tissue), and the brain free-glucose turnover time (2.96 plus or minus 1.98 min). author

scholarly journals Circulating tPA contributes to neurovascular coupling by a mechanism involving the endothelial NMDA receptors

2019 ◽  
Vol 40 (10) ◽  
pp. 2038-2054 ◽  
Author(s):  
Antoine Anfray ◽  
Antoine Drieu ◽  
Vincent Hingot ◽  
Yannick Hommet ◽  
Mervé Yetim ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Neurovascular Unit ◽  
Neurovascular Coupling ◽  
Laser Speckle ◽  
Tissue Type ◽  
Blood Flow Increase ◽  
The Brain

The increase of cerebral blood flow evoked by neuronal activity is essential to ensure enough energy supply to the brain. In the neurovascular unit, endothelial cells are ideally placed to regulate key neurovascular functions of the brain. Nevertheless, some outstanding questions remain about their exact role neurovascular coupling (NVC). Here, we postulated that the tissue-type plasminogen activator (tPA) present in the circulation might contribute to NVC by a mechanism dependent of its interaction with endothelial N-Methyl-D-Aspartate Receptor (NMDAR). To address this question, we used pharmacological and genetic approaches to interfere with vascular tPA-dependent NMDAR signaling, combined with laser speckle flowmetry, intravital microscopy and ultrafast functional ultrasound in vivo imaging. We found that the tPA present in the blood circulation is capable of potentiating the cerebral blood flow increase induced by the activation of the mouse somatosensorial cortex, and that this effect is mediated by a tPA-dependent activation of NMDAR expressed at the luminal part of endothelial cells of arteries. Although blood molecules, such as acetylcholine, bradykinin or ATP are known to regulate vascular tone and induce vessel dilation, our present data provide the first evidence that circulating tPA is capable of influencing neurovascular coupling (NVC).

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