scholarly journals Mechanisms of Brain Ion Homeostasis during Acute and Chronic Variations of Plasma Potassium

1995 ◽  
Vol 15 (2) ◽  
pp. 336-344 ◽  
Author(s):  
Walter Stummer ◽  
A. Lorris Betz ◽  
Richard F. Keep
Keyword(s):  
Blood Brain Barrier ◽  
Ion Homeostasis ◽  
Plasma Potassium ◽  
Brain Barrier ◽  
Intracellular Space ◽  
Blood Brain ◽  
Permeability Surface ◽  
Ion Contents ◽  
Potassium Influx ◽  
Parenchymal Cells

Brain and CSF potassium concentrations are well regulated during acute and chronic alterations of plasma potassium. In a previous study, we have shown that during chronic perturbations, regulation is achieved by appropriate adaptation of potassium influx, but that the degree of such adaptation during acute perturbations is much less. To elucidate further potential regulatory mechanisms, rats were rendered acutely or chronically hyper- or hypokalemic (range 2.7–7.6 m M). Measurements were made of brain and CSF water and ion contents to examine whether regulation occurred by modulation of K+ uptake into parenchymal cells. Furthermore, the permeability-surface area products (PSs) of 22Na+ were determined, because changes in K+ efflux via Na+,K+-ATPase on the brain-facing side of the blood–brain barrier might be reflected in modified Na+ permeability. Brain and CSF K+ concentrations and Na PS were all independent of chronic changes in plasma K+ and acute hypokalemia, suggesting that neither modulation of parenchymal K+ uptake nor K+ efflux via the Na+,K+-ATPase is involved in extracellular K+ regulation in these conditions. In contrast, Na PSs were increased by 40% (p < 0.05) in acute hyperkalemia. This was accompanied by a slight loss of tissue K+ and water from the intracellular space. These results suggest that increased potassium influx in acute hyperkalemia is compensated by stimulation of K+ efflux via Na+,K+-ATPase. A slight degree of overstimulation, as indicated by a net loss of tissue K+, leads us to hypothesize that other factors, apart from the kinetic characteristics of Na+,K+-ATPase, may regulate this enzyme at the blood–brain barrier.

Bidirectional saturable transport of LHRH across the blood-brain barrier

1991 ◽  
Vol 261 (3) ◽  
pp. E312-E318 ◽  
Author(s):  
C. M. Barrera ◽  
A. J. Kastin ◽  
M. B. Fasold ◽  
W. A. Banks
Keyword(s):  
Blood Brain Barrier ◽  
Ovarian Function ◽  
Brain Barrier ◽  
Multiple Time ◽  
Blood Brain ◽  
Permeability Surface ◽  
Cerebrovascular Permeability ◽  
The Difference ◽  
Single Time Point ◽  
Time Point

Systemic administration of luteinizing hormone-releasing hormone (LHRH) in rats has been found to influence behavior independently of pituitary or ovarian function. A previous study has shown that LHRH can cross the blood-brain barrier in one direction, but it was not known whether this was due to a saturable transport system. The rate of entry of 125I-labeled LHRH from blood to brain was determined by two different single-pass methods of carotid perfusion. The first, a multiple time point method, measures Ki from the slope of the linear regression when brain-to-blood ratios of radioiodinated LHRH are plotted against time. Saturable transport was determined by the difference between the Ki of rats perfused with 125I-LHRH (12.51 X 10(-3) mg.g-1.min-1) vs. rats perfused with 125I-LHRH and unlabeled LHRH (10 nmol/ml; 2.20 X 10(-3) ml.g-1.min-1). The inhibition by the unlabeled peptide was statistically significant (P less than 0.001). The second method, a single time point technique, measures the cerebrovascular permeability-surface area coefficient (PA). Saturable transport was determined in rats by the competition of unlabeled LHRH with 125I-LHRH. The PA value for 125I-LHRH (20.00 X 10(-3) ml.g-1.min-1) was significantly greater (P less than 0.05) than for 125I-LHRH with the addition of 10 nmol/ml unlabeled LHRH (4.14 X 10(-3) ml.g-1.min-1). Saturable transport of LHRH from brain to blood in mice was also determined.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood-brain barrier permeability to sucrose and dextran after osmotic opening

1984 ◽  
Vol 247 (4) ◽  
pp. R634-R638 ◽  
Author(s):  
Y. Z. Ziylan ◽  
P. J. Robinson ◽  
S. I. Rapoport
Keyword(s):  
Blood Brain Barrier ◽  
Brain Regions ◽  
Brain Barrier ◽  
Differential Rate ◽  
Barrier Permeability ◽  
Blood Brain Barrier Permeability ◽  
Size Dependent ◽  
Blood Brain ◽  
Permeability Surface ◽  
Brain Barrier Permeability

Regional cerebrovascular permeability-surface area (PA) products were calculated for two nonelectrolyte tracers differing considerably in molecular weight and size [( 14C]sucrose: mol wt 340 daltons, radius 5 A; and [3H]dextran: mol wt approximately 79,000 daltons, radius approximately 65 A) in control (uninfused) rats and in rats 6, 35, and 55 min after the blood-brain barrier was opened by a 30-s infusion of 1.8 molal L(+)-arabinose into a carotid artery. In control brain regions, mean PA for [14C]sucrose was 10(-5) s-1, whereas PA was not measurable for [3H]dextran. Six minutes after arabinose infusion, PA for both substances increased dramatically to 10(-4) s-1 or more; PA then declined at 35 and 55 min after arabinose infusion, but more markedly for [3H]dextran than for [14C]sucrose. The results demonstrate a size-dependent, differential rate of closure of the blood-brain barrier after osmotic opening. This is shown to be consistent with a pore model with bulk flow for blood-brain barrier permeability after osmotic opening.

scholarly journals Nicotine Raises the Influx of Permeable Solutes across the Rat Blood—Brain Barrier with Little or No Capillary Recruitment

1995 ◽  
Vol 15 (4) ◽  
pp. 687-698 ◽  
Author(s):  
J.-L. Chen ◽  
L. Wei ◽  
D. Bereczki ◽  
F.-J. Hans ◽  
T. Otsuka ◽  
...  
Keyword(s):  
Blood Flow ◽  
Blood Brain Barrier ◽  
Brain Barrier ◽  
Brain Areas ◽  
Nicotine Treatment ◽  
Influx Rate ◽  
Capillary Recruitment ◽  
Blood Brain ◽  
Solute Uptake ◽  
Permeability Surface

Nicotine (1.75 mg/kg s.c.) was administered to rats to raise local CBF (lCBF) in various parts of the brain, test the capillary recruitment hypothesis, and determine the effects of this increase in lCBF on local solute uptake by brain. lCBF as well as the local influx rate constants ( K1) and permeability-surface area ( PS) products of [14C]antipyrine and [14C]-3- O-methyl-d-glucose (30MG) were estimated by quantitative autoradiography in 44 brain areas. For this testing, the finding of significantly increased PS products supports the capillary recruitment hypothesis. In 17 of 44 areas, nicotine treatment increased lCBF by 30–150%, K1 of antipyrine by 7–40%, K1 of 30MG by 5–27%, PS product of antipyrine by 0–20% (mean 7%), and PS product of 30MG by 0–23% (mean 8%). Nicotine had no effect on blood flow or influx in the remaining 27 areas. The increases in lCBF and K1 of antipyrine were significant, whereas those in K1 of 30MG and in PS for both antipyrine and 30MG were not statistically significant. The lack of significant changes in PS products implies that in brain areas where nicotine increased blood flow: (a) essentially no additional capillaries were recruited and (b) blood flow within brain capillary beds rises by elevating linear velocity. The K1 results indicate that the flow increase generated by nicotine will greatly raise the influx and washout rates of highly permeable materials, modestly elevate those of moderately permeable substances, and negligibly change those of solutes with extraction fractions of <0.2, thereby preserving the barrier function of the blood–brain barrier.

Acute upregulation of blood-brain barrier glucose transporter activity in seizures

2000 ◽  
Vol 279 (3) ◽  
pp. H1346-H1354 ◽  
Author(s):  
Eain M. Cornford ◽  
Eddy V. Nguyen ◽  
Elliot M. Landaw
Keyword(s):  
Blood Brain Barrier ◽  
Glucose Transporter ◽  
Brain Barrier ◽  
Brain Extraction ◽  
Blood Brain ◽  
Half Saturation Constant ◽  
Permeability Surface ◽  
Permeability Increase ◽  
Cortical Regions ◽  
Area Product

Brain extraction of 18F-labeled 2-fluoro-2-deoxy-d-glucose (FDG) was significantly higher in pentylene tetrazole (PTZ)-treated rats (32 ± 4%) than controls (25 ± 4%). The FDG permeability-surface area product ( PS) was also significantly higher with PTZ treatment (0.36 ± 0.05 ml · min−1 · g−1) than in controls (0.20 ± 0.06 ml · min−1 · g−1). Cerebral blood flow rates were also elevated by 50% in seizures. The internal carotid artery perfusion technique indicated mean [14C]glucose clearance (and extraction) was increased with PTZ treatment, and seizures increased the PS by 37 ± 16% ( P < 0.05) in cortical regions. Because kinetic analyses suggested the glucose transporter half-saturation constant ( K m) was unchanged by PTZ, we derived estimates of 1) treated and 2) control maximal transporter velocities ( V max) and 3) a single K m. In cortex, the glucose transporter V max was 42 ± 11% higher ( P < 0.05) in PTZ-treated animals (2.46 ± 0.34 μmol · min−1 · g−1) than in control animals (1.74 ± 0.26 μmol · min−1 · g−1), and the K m = 9.5 ± 1.6 mM. Blood-brain barrier (BBB) V max was 31 ± 10% greater ( P < 0.05) in PTZ-treated (2.36 ± 0.30 μmol · min−1 · g−1) than control subcortex (1.80 ± 0.25 μmol · min−1 · g−1). We conclude acute upregulation of BBB glucose transport occurs within 3 min of an initial seizure. Transporter V max and BBB glucose permeability increase by 30–40%.

scholarly journals Extraction of [99mTc]—d,l-HM-PAO across the Blood—Brain Barrier

1988 ◽  
Vol 8 (1_suppl) ◽  
pp. S44-S51 ◽  
Author(s):  
Allan R. Andersen ◽  
Hans Friberg ◽  
Karen B. M. Knudsen ◽  
David I. Barry ◽  
Olaf B. Paulson ◽  
...  
Keyword(s):  
Blood Brain Barrier ◽  
Experimental Period ◽  
Brain Barrier ◽  
Initial Slope ◽  
Brain Capillaries ◽  
Time Profiles ◽  
Blood Brain ◽  
Permeability Surface ◽  
Bolus Size ◽  
Area Product

The initial extraction ( E) across the blood–brain barrier (BBB) of [99mTc]– d,l-HM-PAO after intracarotid injection was measured in 14 Wistar rats and 6 patients using the double indicator, single injection method with Na-24 as the cotracer. In both series, cerebral blood flow (CBF) was measured using the initial slope of the xenon-133 washout curve after intracarotid bolus injection. In rats, bolus size (20 or 120 μl), bolus type (saline or 10% albumin), or CBF were changed. First-pass extraction was dependent on CBF ( p < 0.001): With a small bolus of saline and at resting CBF (0.75 ml/g/min), E was 0.81, decreasing to 0.56 at a high CBF (1.5 ml/g/min). The calculated permeability surface area product ( PS) increased linearly from 1.2 to 1.5 ml/g/min when CBF increased from 0.8 to 1.5 ml/g/min (p < 0.01). E was found to increase when the bolus volume of saline was increased from 20 to 120 μl, while using a 120 μl bolus containing 10% albumin resulted in a decrease in E. This suggests that HM-PAO binding to albumin is not totally and rapidly reversible during a single passage through brain capillaries and that binding to blood elements may reduce the apparent extraction across brain capillaries. In patients using a bolus of 1 ml saline, E decreased linearly with increasing CBF ( r = −0.81, p < 0.001). For a CBF of 0.59 ml/g/min and an average apparent E of 0.72, an apparent PS product of 0.76 ml/g/min was calculated. Analysis of the apparent E vs. time profiles indicated a backdiffusion of the tracer during the experimental period. This could lead to a small underestimation of the actual extraction values.

scholarly journals Functional NHE1 expression is critical to blood brain barrier integrity and sumatriptan blood to brain uptake

2019 ◽  
Author(s):  
Erika Liktor-Busa ◽  
Kiera T. Blawn ◽  
Kathryn L. Kellohen ◽  
Beth M. Wiese ◽  
Vani Verkhovsky ◽  
...  
Keyword(s):  
Blood Brain Barrier ◽  
Ion Homeostasis ◽  
Early Time ◽  
Female Rats ◽  
Brain Barrier ◽  
Barrier Integrity ◽  
Blood Brain ◽  
Blood Brain Barrier Integrity

AbstractDisruption of blood-brain barrier integrity and dramatic failure of brain ion homeostasis including fluctuations of pH occurs during cortical spreading depression (CSD) events associated with several neurological disorders, including migraine with aura, traumatic brain injury and stroke. NHE1 is the primary regulator of pH in the central nervous system. The goal of the current study was to investigate the role of sodium-hydrogen exchanger type 1 (NHE1) in blood brain barrier (BBB) integrity during CSD events and the contributions of this antiporter on xenobiotic uptake. Using immortalized cell lines, pharmacologic inhibition and genetic knockdown of NHE1 mitigated the paracellular uptake of radiolabeled sucrose implicating functional NHE1 in BBB maintenance. In contrast, loss of functional NHE1 in endothelial cells facilitated uptake of the anti-migraine therapeutic, sumatriptan. In female rats, cortical KCl but not aCSF selectively reduced total expression of NHE1 in cortex and PAG with limited impact on trigeminal ganglia or trigeminal nucleus caudalis suggesting in vitro observations may have a significance in vivo. Pharmacological inhibition of NHE1 prior to cortical manipulations enhanced the efficacy of sumatriptan at early time-points but induced facial sensitivity alone. Overall, our results suggest that dysregulation of NHE1 contributes to breaches in BBB integrity, drug penetrance, and the behavioral sensitivity to the antimigraine agent, sumatriptan.

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