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

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.

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Cerebral blood flow in intoxicated newborn piglets

Canadian Journal of Physiology and Pharmacology ◽

10.1139/y87-018 ◽

1987 ◽

Vol 65 (1) ◽

pp. 92-95 ◽

Cited By ~ 2

Author(s):

Cara J. MacIntyre ◽

Bill Y. Ong ◽

Daniel S. Sitar

Keyword(s):

Blood Flow ◽

Cerebral Blood Flow ◽

Basal Ganglia ◽

Brain Regions ◽

Ethanol Exposure ◽

Blood Flows ◽

Arterial Blood ◽

Regional Blood Flows ◽

Blood Pressures ◽

And Control

Ethanol exposure in the neonatal period causes impaired brain growth and altered adult behaviour in rats. One possible mechanism may be altered cerebral perfusion caused by ethanol intoxication. We assessed the effects of ethanol on cerebral blood flow and its autoregulation in 2-day-old piglets. Piglets received ethanol (1.4 g/kg) or an equivalent volume of dextrose 5% in water over 30 min. One hour later, cerebral blood flow was measured using the microsphere technique at resting, elevated, and decreased mean arterial blood pressure. Ethanol-treated piglets had total cerebral blood flows of 88 ± 14, 82 ± 10, and 82 ± 12 mL∙100 g−1∙min−1 (mean ± SE) at mean arterial blood pressures of 12.4 ± 1.1, 15.7 ± 1.5, and 8.2 ± 0.9 kPa. Corresponding values in control piglets were 82 ± 14, 78 ± 4, and 82 ± 7 mL∙100 g−1∙min−1 at mean arterial blood pressures of 10.5 ± 1.5, 14.0 ± 1.2, and 7.7 ± 1.1 kPa. At resting arterial blood pressures, regional blood flows to basal ganglia, cortex, brainstem, and cerebellum in ethanol-treated piglets were 123 ± 21, 90 ± 16, 94 ± 17, and 77 ± 12 mL∙100 g−1∙min−1, respectively. Corresponding regional blood flows for the control piglets were 118 ± 16, 85 ± 15, 76 ± 16, and 76 ± 16 mL∙100 g−1∙min−1. Blood flow to basal ganglia was greater than to other brain regions in both ethanol-treated and control piglets (P < 0.01). Total and regional blood flows remained unchanged with altered mean arterial blood pressures, indicating normal autoregulation of cerebral blood flow in both ethanol-treated and control piglets.

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Adenosine and cerebral capillary perfusion and blood flow during middle cerebral artery occlusion

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.1989.257.5.h1656 ◽

1989 ◽

Vol 257 (5) ◽

pp. H1656-H1662

Author(s):

M. Anwar ◽

H. R. Weiss

Keyword(s):

Blood Flow ◽

Cerebral Blood Flow ◽

Middle Cerebral Artery ◽

Middle Cerebral Artery Occlusion ◽

Cerebral Artery ◽

Brain Regions ◽

Artery Occlusion ◽

Capillary Perfusion ◽

Arterial Blood ◽

Cerebral Artery Occlusion

The effects of adenosine on regional cerebral blood flow and indexes of the total and perfused microvascular bed were studied after 1 h of middle cerebral artery occlusion in the anesthetized rat. Iodo[14C]antipyrine was used to determine cerebral blood flow. Fluorescein isothiocyanate-dextran was used to study the perfused microvasculature, and an alkaline phosphatase stain was used to identify the total bed. Mean arterial blood pressure was significantly reduced by adenosine. Cerebral blood flow increased significantly by 75%, except in the flow-restricted cortex where flow averaged 28 +/- 15 (SD) ml.min-1.100 g-1 in control and 34 +/- 33 ml.min-1.100 g-1 in adenosine-treated animals. No significant regional structural differences were observed within the microvascular beds of the two groups. The percentage of the microvascular volume perfused increased significantly in all brain regions in the adenosine-treated rats, including the flow-restricted cortex. The percent perfused arteriolar volume in the flow-restricted cortex was 30 +/- 12% in control and 95 +/- 3% in adenosine-treated animals. Similar values for the capillary bed were 22 +/- 10% in control and 54 +/- 3% in adenosine-treated rats. These results indicate a maintenance of flow with a reduction in diffusion distances in the flow-restricted cortex after treatment with adenosine.

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Ischemia Reduces Blood-to-Brain Glucose Transport in the Gerbil

Journal of Cerebral Blood Flow & Metabolism ◽

10.1038/jcbfm.1983.27 ◽

1983 ◽

Vol 3 (2) ◽

pp. 200-206 ◽

Cited By ~ 23

Author(s):

A. Lorris Betz ◽

Fausto Iannotti ◽

Julian T. Hoff

Keyword(s):

Cerebral Cortex ◽

Basal Ganglia ◽

Carotid Artery ◽

Glucose Transport ◽

Artery Occlusion ◽

Carotid Artery Occlusion ◽

Carotid Occlusion ◽

Brain Glucose ◽

Bilateral Carotid ◽

Common Carotid Artery Occlusion

The effect of carotid occlusion on cerebral blood flow (CBF), brain plasma volume for sucrose ( Vplsuc), and unidirectional transport of glucose from blood to brain was measured in four regions of gerbil brain. Unilateral common carotid artery occlusion caused a variable decrease in CBF to the ipsilateral cerebral cortex and basal ganglia, with no change in CBF to the contralateral structures, cerebellum, or brainstem. One hour of bilateral carotid artery occlusion reduced flow to near zero in the cerebral cortex and to 30% of control in the basal ganglia, while increasing CBF to the cerebellum and brainstem. There was a significant decrease in the Vplsuc of the cerebral cortex and basal ganglia after 1 h of ischemia, perhaps due to compression of the intravascular space by edema fluid. Blood-to-brain glucose transport, 1 min after release from 1 h of bilateral carotid occlusion, was decreased in the cerebral cortex and basal ganglia, but not in the cerebellum or brainstem. These data indicate that 1 h of complete or incomplete ischemia reduces the rate of unidirectional glucose transport from blood to brain.

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Acute Brain Injury Is Associated With Prolonged Suppression of Cerebral Blood Flow Oscillations

Neurosurgery ◽

10.1093/neuros/nyz310_680 ◽

2019 ◽

Vol 66 (Supplement_1) ◽

Author(s):

Ryan M Jamiolkowski ◽

Wesley Baker ◽

W Andrew Kofke ◽

Ramani Balu

Keyword(s):

Blood Flow ◽

Cerebral Blood Flow ◽

Brain Injury ◽

Frequency Band ◽

Prognostic Significance ◽

Low Frequency ◽

Brain Regions ◽

Total Power ◽

Blood Flow Oscillations ◽

Arterial Blood

Abstract INTRODUCTION Low-frequency oscillations (LFOs, < 0.1 Hz) in cerebral blood flow (CBF) reflect changes in the coordinated activity of neuronal assemblies. Synchronized LFOs across multiple brain regions can be identified using magnetic resonance imaging to reveal functionally connected networks; however, how LFOs are altered by brain injury is largely unknown. METHODS We quantified changes in LFO magnitude over time in brain-injured patients where CBF was recorded continuously using invasive thermal diffusion flowmetry. Intracranial pressure (ICP), brain tissue oxygen (PbO2), and arterial blood pressure (ABP) were recorded concurrently in all patients. For each epoch of uninterrupted CBF data, the power spectral density within the 0.05 to 0.1 Hz frequency band was calculated. Periods of LFO suppression were defined as occurring when equal to 10% of the total power across all frequencies occurred in the 0.05 to 1 Hz frequency band. Average values of CBF, ICP, PbO2, and ABP were compared between suppressed and nonsuppressed epochs across all patients. RESULTS Twenty-five patients were included in this retrospective observational study. LFO suppression was associated with a lower average CBF (11.3 mL/100 g/min suppressed vs 31.6 mL/100 g/min unsuppressed, P < .0001) and lower average PbO2 (21.6 mm Hg suppressed vs 31.0 mm Hg unsuppressed, P < .0001). In a subset of patients, LFO suppression was associated with intracranial hypertension (ICP 25-60 mm Hg). Patients that regained consciousness and were discharged to acute rehab had a lower median fraction of time spent in the suppressed state (0.03 rehab vs 0.67 death/nursing home, P = .053). CONCLUSION Brain injury is associated with the suppression of low-frequency CBF fluctuations. LFO suppression is associated with periods of physiological distress and may provide a sensitive marker of disrupted brain function. The degree of LFO suppression may have a prognostic significance, and the re-emergence of LFOs after a period of suppression may provide a marker of return of consciousness after coma.

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Prolonged Effects of Cholinesterase Inhibition with Eptastigmine on the Cerebral Blood Flow-Metabolism Ratio of Normal Rats

Journal of Cerebral Blood Flow & Metabolism ◽

10.1038/jcbfm.1993.89 ◽

1993 ◽

Vol 13 (4) ◽

pp. 702-711 ◽

Cited By ~ 20

Author(s):

Oscar U. Scremin ◽

A. M. Erika Scremin ◽

Deborah Heuser ◽

Raymond Hudgell ◽

Elsa Romero ◽

...

Keyword(s):

Blood Flow ◽

Cerebral Blood Flow ◽

Glucose Utilization ◽

Regression Line ◽

Brain Regions ◽

Metabolic Effects ◽

Cholinesterase Inhibition ◽

Arterial Blood ◽

A Value ◽

Similar Dose

The cerebrovascular and metabolic effects of the novel cholinesterase inhibitor eptastigmine were tested in conscious rats. The drug was administered by single intravenous injection, and blood flow or glucose utilization were assessed in 38 brain regions by quantitative autoradiographic techniques. A dose-dependent increase in regional cerebral blood flow (rCBF) was obtained for i.v. doses ranging from 0.5 to 3 mg kg−1. Forty minutes after the dose of 1.5 mg kg−1, average rCBF of the 38 regions studied was (mean ± SD) 2.62 ± 0.62 ml g−1 min−1, a value significantly higher than that of saline-injected controls (1.46 ± 0.26; p < 0.005). In contrast, a similar dose of eptastigmine did not significantly alter regional cerebral glucose utilization (rCGU) (0.90 ± 0.21 μmol g−1 min−1) when compared with saline-injected controls (0.99 ± 0.08 μmol g−1 min−1). A linear correlation between rCBF and rCGU was observed both in saline ( r = 0.871) and eptastigmine ( r = 0.873)-injected animals but the slope of the regression line of rCBF on rCGU was significantly higher (p < 0.01) in the eptastigmine group (2.863 ± 0.266) than in the controls that received saline (1.00 ± 0.094). The cerebral vasodilatation induced by eptastigmine peaked at 40 min after drug administration. No toxic signs were observed at the doses used. Mean arterial blood pressure decreased after 0.5 mg kg−1 (control = 109.3 ± 10.56 mm Hg; eptastigmine = 96.6 ± 8.10 mm Hg) but did not differ from control at the higher doses. It is concluded that eptastigmine induces a long-lasting increase in rCBF and a significant enhancement of the rCBF:rCGU ratio in most regions. The results suggest an important role of endogenous acetylcholine in the control of cerebral perfusion.

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Catecholamines and the relationship between cerebral blood flow and glucose use

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.1986.251.4.h824 ◽

1986 ◽

Vol 251 (4) ◽

pp. H824-H833 ◽

Cited By ~ 2

Author(s):

U. I. Tuor ◽

L. Edvinsson ◽

J. McCulloch

Keyword(s):

Blood Flow ◽

Cerebral Blood Flow ◽

Moderate Hypertension ◽

Brain Regions ◽

Dopamine Infusion ◽

Arterial Blood ◽

Norepinephrine Infusion ◽

Bbb Permeability ◽

The Relationship ◽

The Brain

The effects of hypertension induced by norepinephrine and dopamine infusion on the relationship between local cerebral blood flow (CBF) and local glucose use (GU) were examined in rats with the use of quantitative autoradiographic techniques. After rats recovered from anesthesia, dopamine or norepinephrine was infused at a rate that ensured moderate hypertension [mean arterial blood pressure (MABP) approximately 150 mmHg]. During dopamine infusion (approximately 200 micrograms X kg-1 X min-1), overall CBF-to-GU ratio throughout the brain was elevated (P less than 0.0001) when compared with saline controls. In contrast, during norepinephrine infusion (approximately 10 micrograms X kg-1 X min-1), the overall CBF-to-GU relationship was not altered significantly. The differential effect of the catecholamines was a consequence of the marked increases in local CBF and moderate decreases in GU observed during dopamine infusion, whereas during norepinephrine administration CBF and GU were not significantly altered in most brain regions. Blood-brain barrier (BBB) permeability was increased during moderate hypertension induced by dopamine and not when induced by norepinephrine. During extreme hypertension (MABP greater than 165 mmHg), heterogeneous increases in CBF and BBB permeability occurred (e.g., in the cerebellum and thalamus). Thus the cerebrovascular response to catecholamine infusion was critically dependent on the agent administered, the level of hypertension achieved, and the brain region examined.

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

Journal of Cerebral Blood Flow & Metabolism ◽

10.1097/00004647-200106000-00003 ◽

2001 ◽

Vol 21 (6) ◽

pp. 653-663 ◽

Cited By ~ 100

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.

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