Kinetics of movement of iodide, sucrose, inulin and radio‐iodinated serum albumin in the central nervous system and cerebrospinal fluid of the rat

Reed, Donal J.; Woodbury, Dixon M.

doi:10.1113/jphysiol.1963.sp007298

Cited by 132 publications

(60 citation statements)

References 29 publications

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“…The formula for the rate constants and the distribution spaces for the various compartments of the different models that are used in this paper are derived in Appendix II. Reed & Woodbury, 1963), and corroborated in this laboratory, that the fraction of water in plasma, Pw/P,, is equal to 0-93. Using this correction factor in eqn.…”

Section: Methodssupporting

confidence: 63%

“…In light of past work which has consistently demonstrated a small 571 VICTOR LEVIN AND CLIFFORD S. PATLAK 'perivascular brain space' of 2-5% (Davson, Kleeman & Levin, 1961;Ferguson & Woodbury, 1969;Katzman, Schimmel & Wilson, 1968;Reed & Woodbury, 1963;Sisson & Oldendorf, 1971), it seemed reasonable to assume that the exchange of 24Na was from blood to 'perivascular space' and from blood to extracellular space and thence to intracellular space. This interpretation resulted in our finding three 24Na spaces of approximately 2, 22 and 6 %.…”

Section: "Mna Kinetics In Rat Tissuesmentioning

confidence: 99%

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A compartmental analysis of ²⁴Na kinetics in rat cerebrum, sciatic nerve and cerebrospinal fluid

Levin¹,

Patlak²

1972

The Journal of Physiology

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SUMMARY1. The kinetics of 24Na exchange in rat cerebrospinal fluid, brain and sciatic nerve were studied during steady-state plasma isotope conditions. The entrance of 24Na into brain and sciatic nerve was found to fit a three compartmental model. Using newly derived equations for compartmental analysis, the first compartment 24Na space of brain was found to be about 22 % and the second compartment space about 6 %; the corresponding sciatic nerve spaces were 26 and 11 %, respectively. In the discussion, arguments are presented that suggest that the first compartment is the extracellular space (ECS) and the second compartment is the intracellular space. The tj for compartmental equilibration between plasma and brain ECS was 2 hr and from ECS to intracellular space 14 hr; in nerve the respective ti's were i hr and 10 hr.2. A third compartment of 18 % was found in sciatic nerve which was interpreted to be anatomically confined to the epi-and perineurium; in brain the corresponding space was 2 % and was felt to be anatomically and kinetically an inactive closed compartment in parallel with the blood.3. There were two tj's for plasma-c.s.f. 24Na equilibration of less than 10 min and 2 hr.4. Profiles of brain, from cortex to ventricle, at 6 min, demonstrated a gradient of decreasing 24Na radioactivity from ventricle to cortex.

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Section: Methodssupporting

confidence: 63%

Section: "Mna Kinetics In Rat Tissuesmentioning

confidence: 99%

A compartmental analysis of ²⁴Na kinetics in rat cerebrum, sciatic nerve and cerebrospinal fluid

Levin¹,

Patlak²

1972

The Journal of Physiology

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“…Furthermore, the estimated volume of the vascular plasma space seems to be dependent on the size of the vascular tracer used. Reports show that vascular tracers with a molecular size of r20 kDa occupy a 60% to 90% greater volume of brain capillaries in rats than tracers > 40 kDa (Reed and Woodbury, 1963;Sarna et al, 1977;Smith et al, 1988). This suggests that plasma water has a larger volume of distribution within the brain capillaries than do plasma proteins (a 1 -acid glycoprotein 42 kDa, albumin 67 kDa, lipoproteins 200 to 2,400 kDa (Rowland and Tozer, 1995)).…”

Section: Discussionmentioning

confidence: 99%

“…It represents an apparent plasma volume with a protein concentration equal to arterial plasma. H-inulin and 14 C-dextran are not bound to plasma proteins or to erythrocytes and do not measurably cross the BBB within the estimated time of the experiment (Reed and Woodbury, 1963;Smith et al, 1988;Todd et al, 1993). H-inulin and 14 C-dextran were dissolved in saline and dialyzed overnight in Spectra/Pore 1,000 kDa molecular weight cutoff membrane tubing (Spectrum Laboratories, Rancho Dominguez, CA, USA), to remove radiolabeled impurities of low molecular weight.…”

Section: Determination Of Vascular Spacesmentioning

confidence: 99%

Improved Measurement of Drug Exposure in the Brain Using Drug-Specific Correction for Residual Blood

Fridén

Ljungqvist

Middleton

et al. 2009

J Cereb Blood Flow Metab

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A major challenge associated with the determination of the unbound brain-to-plasma concentration ratio of a drug (K p,uu,brain ), is the error associated with correction for the drug in various vascular spaces of the brain, i.e., in residual blood. The apparent brain vascular spaces of plasma water (V water , 10.3 lL/g brain), plasma proteins (V protein , 7.99 lL/g brain), and the volume of erythrocytes (V er , 2.13 lL/g brain) were determined and incorporated into a novel, drug-specific correction model that took the drug-unbound fraction in the plasma (f u,p ) into account. The correction model was successfully applied for the determination of K p,uu,brain for indomethacin, loperamide, and moxalactam, which had potential problems associated with correction. The influence on correction of the drug associated with erythrocytes was shown to be minimal. Therefore, it is proposed that correction for residual blood can be performed using an effective plasma space in the brain (V eff ), which is calculated from the measured f u,p of the particular drug as well as from the estimates of V water and V protein , which are provided in this study. Furthermore, the results highlight the value of determining K p,uu,brain with statistical precision to enable appropriate interpretation of brain exposure for drugs that appear to be restricted to the brain vascular spaces.

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“…route. A number of antisera (Turnbull and Rivier, 1998), cytokines (Chen et al, 1997;Chen and Reichlin, 1999) and large molecules such as albumin (Reed and Woodbury, 1963) have been injected centrally and had their passage to the periphery traced. All are detectable in plasma within 5-30 min following injection.…”

Section: Crh þ Astressin B Pretreatmentmentioning

confidence: 99%

Corticotropin-Releasing Hormone Antagonists, Astressin B and Antalarmin: Differing Profiles of Activity in Rhesus Monkeys

Broadbear

Winger

Rivier

et al. 2004

Neuropsychopharmacol

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The present study compares the activity of two chemically distinct corticotropin-releasing hormone (CRH) antagonists at the level of the pituitary gland in rhesus monkeys, using exogenous CRH-stimulated increases in adrenocorticotropin (ACTH) and cortisol. Of chief interest was whether the CRH-R1-selective pyrrolopyrimidine, antalarmin, shown previously to have activity in the central nervous system (CNS), would differ in its antagonist profile from the CRH-R1-& 2-selective peptide, astressin B, which is unlikely to have access to the CNS following systemic administration. Nine rhesus monkeys (eight male), each with an indwelling venous catheter, were subjects in this study. Astressin B (0.001, 0.003, 0.03, 0.1, and 0.3 mg/kg) or antalarmin (1.0, 3.2, and 10 mg/kg) was administered as an intravenous (i.v.) pretreatment 15 min prior to administration of 1 or 10 mg/kg i.v. CRH. Antalarmin (10 mg/kg) was also administered alone on six occasions and its effects on behavior as well as on ACTH and cortisol levels were measured. Astressin B was assessed following i.v. and intracisternal (i.c.) administration. Astressin B dose-dependently abolished the CRH-stimulated ACTH and cortisol responses, with an antagonist effect lasting in excess of 24 h. Astressin B was approximately 300-times more potent when given i.c. than when it was administered via the i.v. route. By contrast, antalarmin antagonized the effects of CRH on ACTH but not cortisol at 1.0 and 3.2 mg/kg. At a larger dose, antalarmin stimulated ACTH and cortisol release and produced behavioral sedation. These latter effects diminished with repeated administration of antalarmin. The differences between astressin B and antalarmin may be due either to non-CRH receptormediated effects of antalarmin or to a complex interaction of antalarmin's effects at both central and peripheral CRH receptors.

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Kinetics of movement of iodide, sucrose, inulin and radio‐iodinated serum albumin in the central nervous system and cerebrospinal fluid of the rat

Cited by 132 publications

References 29 publications

A compartmental analysis of ²⁴Na kinetics in rat cerebrum, sciatic nerve and cerebrospinal fluid

A compartmental analysis of ²⁴Na kinetics in rat cerebrum, sciatic nerve and cerebrospinal fluid

Improved Measurement of Drug Exposure in the Brain Using Drug-Specific Correction for Residual Blood

Corticotropin-Releasing Hormone Antagonists, Astressin B and Antalarmin: Differing Profiles of Activity in Rhesus Monkeys

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Kinetics of movement of iodide, sucrose, inulin and radio‐iodinated serum albumin in the central nervous system and cerebrospinal fluid of the rat

Cited by 132 publications

References 29 publications

A compartmental analysis of 24Na kinetics in rat cerebrum, sciatic nerve and cerebrospinal fluid

A compartmental analysis of 24Na kinetics in rat cerebrum, sciatic nerve and cerebrospinal fluid

Improved Measurement of Drug Exposure in the Brain Using Drug-Specific Correction for Residual Blood

Corticotropin-Releasing Hormone Antagonists, Astressin B and Antalarmin: Differing Profiles of Activity in Rhesus Monkeys

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A compartmental analysis of ²⁴Na kinetics in rat cerebrum, sciatic nerve and cerebrospinal fluid

A compartmental analysis of ²⁴Na kinetics in rat cerebrum, sciatic nerve and cerebrospinal fluid