Rapid changes in extracellular glucose levels and blood flow in the striatum of the freely moving rat

doi:10.1016/0006-8993(93)90373-U

Brain Research

Volume 604, Issues 1–2, 26 February 1993, Pages 225-231

https://doi.org/10.1016/0006-8993(93)90373-U Get rights and content

Abstract

The dynamics of regional cerebral blood flow and brain extracellular glucose were studied in the freely moving rat. These two variables were measured in the striatum during and following both mild tail pinch and resistant stress. Blood flow was monitored using a refinement of the hydrogen clearance technique that allowed repeated measurements at 5-min intervals. A slow stream of hydrogen was directed at the rat's snout for 10–20 s through lightweight tubing attached to the animal's head and detected at a chronically implanted platinum electrode. Extracellular glucose was monitored with microdialysis in a separate group of animals using an on-line, enzyme-based assay that provided 2.5-min time resolution. Mean striatal blood flow 24 h following implantation was 89.9 ± 2.5 ml ·(100g)⁻¹·min⁻¹. A 5-min tail pinch caused flow to increase immediately to 169.5 ± 20 ml ·(100g⁻¹·min⁻¹. In contrast, there was no change in blood flow during restraint stress, although there was a small increase following the end of the stress. Significant increases in blood flow were also observed in the striatum during periods of eating and grooming. Extracellular glucose levels increased following both forms of stress, to a maximum of 170 ± 22% of baseline with restraint compared to 110 ± 2% with tail pinch. In both cases, the increase occured after the stress had ended and persisted while blood flow returned to basal levels.

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The primary energy source for the brain is glucose, and a continuous supply is required for the brain to work longer. This study aimed to verify the effects of palatinose on attention and cerebral blood flow in healthy adults.
This randomized, double-blind, placebo-controlled crossover study included 64 healthy Japanese adults. Participants performed the Digit Vigilance Task (DVT) 60 min pre-ingestion (14:00) and 0 (15:00), 60 (16:00), 120 (17:00), and 180 (18:00) min after ingestion of 10 g of either palatinose or glucose. Cerebral blood flow was measured using a wearable 2CH functional near-infrared spectrometer (fNIRS) during each DVT. The participants underwent the Uchida-Kraepelin (UK) test between each DVT to control for fatigue.
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By using ceramic based platinum microelectrode arrays (Fig. 7 A and B) for which we characterized the O2 monitoring capabilities [173] we have been able to determine the resting levels of pO2 in different brain regions of adult rats. Furthermore, in the hippocampus and starting at a resting [O2] between 6.6 and 22 μM, we demonstrated that with this approach we can monitor activity elicited changes in extracellular pO2: in a tail pinch stress paradigm (Fig. 7C) we observed a transient 15% increase in pO2 supported by the activity dependent hyperemia caused by increase glutamatergic transmission [174]. We have also characterized the exuberant shifts in pO2 which accompany chemically induced status epilepticus [175], including the initial epileptic dip followed by a prolonged hyperoxia resulting from increased O2 consumption followed by hyperemia, respectively (Fig. 7D).
The small and diffusible free radical nitric oxide (^•NO) has fascinated biological and medical scientists since it was promoted from atmospheric air pollutant to biological ubiquitous signaling molecule. Its unique physical chemical properties expand beyond its radical nature to include fast diffusion in aqueous and lipid environments and selective reactivity in a biological setting determined by bioavailability and reaction rate constants with biomolecules. In the brain, ^•NO is recognized as a key player in numerous physiological processes ranging from neurotransmission/neuromodulation to neurovascular coupling and immune response. Furthermore, changes in its bioactivity are central to the molecular pathways associated with brain aging and neurodegeneration. The understanding of ^•NO bioactivity in the brain, however, requires the knowledge of its concentration dynamics with high spatial and temporal resolution upon stimulation of its synthesis. Here we revise our current understanding of the role of neuronal-derived ^•NO in brain physiology, aging and degeneration, focused on changes in the extracellular concentration dynamics of this free radical and the regulation of bioenergetic metabolism and neurovascular coupling.
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Citation Excerpt :
In vitro calibrations were conducted in PBS (pH 7.3) by incrementally increasing the concentration of glucose (Sigma-Aldrich) from 0 to 0.5, 1.0, and 1.5 mM followed by a single addition of ascorbate (250 μM). Within this physiological range of glucose levels (Fellows and Boutelle, 1993; McNay and Gold, 2001), the glucose sensors used in this study produced incremental linear current increases. Mean sensitivity to glucose was 5.54 ± 0.50 nA/0.5 mM at 22-23 °C and 10.87 ± 0.97/0.5 mM nA at 37 °C.
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As an increasing number of common anesthetics (e.g., isofluorane) are known to have vasoactive effects (Ueki et al., 1992; Lindauer et al., 1993; Matta et al., 1999), development of a technique capable of exploring deep within the brain during conscious activity is highly desired. Inert gases are attractive clearance tracers in biological subjects, as gas clearance can make an unlimited number of measurements per subject, detect CBF below the cortex, and perform in both anesthetized and freely-moving animals, all while quantifying CBF in ways that correlate highly with values obtained from competing techniques (Kety, 1951; Pell et al., 2003; Machens et al., 1995; DiResta et al., 1987; Aukland et al., 1964; Fellows and Boutelle, 1993; Lowry et al., 1997). The most affordable clearance gas is H2, introduced through inhalation, injection of H2-saturated saline, or electrolytic generation (Aukland et al., 1964; Stosseck et al., 1974; Young, 1980).
Modern cerebral blood flow (CBF) detection favors the use of either optical technologies that are limited to cortical brain regions, or expensive magnetic resonance. Decades ago, inhalation gas clearance was the choice method of quantifying CBF, but this suffered from poor temporal resolution. Electrolytic H₂ clearance (EHC) generates and collects gas in situ at an electrode pair, which improves temporal resolution, but the probe size has prohibited meaningful subcortical use.
We microfabricated EHC electrodes to an order of magnitude smaller than those existing, on the scale of 100 μm, to permit use deep within the brain.
Novel EHC probes were fabricated. The devices offered exceptional signal-to-noise, achieved high collection efficiencies (40–50%) in vitro, and agreed with theoretical modeling. An in vitro chemical reaction model was used to confirm that our devices detected flow rates higher than those expected physiologically. Computational modeling that incorporated realistic noise levels demonstrated devices would be sensitive to physiological CBF rates.
The reduced size of our arrays makes them suitable for subcortical EHC measurements, as opposed to the larger, existing EHC electrodes that would cause substantial tissue damage. Our array can collect multiple CBF measurements per minute, and can thus resolve physiological changes occurring on a shorter timescale than existing gas clearance measurements.
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^*: Present address: McGill University, Faculty of Medicine, 3655 Drummond Street, Montreal, PQ, Canada H3G 1Y6.

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Rapid changes in extracellular glucose levels and blood flow in the striatum of the freely moving rat

Abstract

The dialysis electrode — a new method for in vivo monitoring

Chem. Comm.

Tail pinch-induced eating, gnawing and licking behavior in rats: dependence on the nigrostriatal dopamine system

Brain Res.

Adrenal demedullation blocks and brain norepinephrine depletion potentiates the hyperglycemic response to a variety of stressors

Brain Res.

Enzyme packed bed system for on-line measurement of glucose, glutamate and lactate in brain microdialysate

Anal. Chem.

In vivo neurochemical effects of tail pinch

J. Neurosci. Methods

Effects of the angiotensin I converting enzyme inhibitor perindopril on cerebral blood flow in awake hypertensive rats

Am. J. Hypertens.

Cerebral blood flow and energy metabolism during stress

Am. J. Physiol.

Relationships between extraction and metabolism of glucose, blood flow and tissue blood volume in regions of rat brain

J. Cereb. Blood Flow Metab.

Diurnal variation of cerebral blood flow in rat hippocampus

Stroke

Extracellular brain glucose levels reflect local neuronal activity: a microdialysis study in awake, freely moving rats

J. Neurochem.

Use of hydrogen for measurement of regional cerebral blood flow — problem of intercompartmental diffusion

Stroke

Transport of essential nutrients across the blood-brain barrier of individual structures