Cerebrospinal fluid and brain extracellular fluid in severe brain trauma

2018 ◽  
pp. 237-258 ◽  
Author(s):  
Raimund Helbok ◽  
Ronny Beer
Keyword(s):  
Cerebrospinal Fluid ◽  
Extracellular Fluid ◽  
Brain Trauma ◽  
Brain Extracellular Fluid

Distribution of H+ and HCO3 minus between CSF and blood during metabolic alkalosis in dogs

1975 ◽  
Vol 228 (4) ◽  
pp. 1141-1144 ◽  
Author(s):  
EG Pavlin ◽  
ttf Hornbein
Keyword(s):  
Cerebrospinal Fluid ◽  
Steady State ◽  
Metabolic Alkalosis ◽  
Extracellular Fluid ◽  
Ion Distribution ◽  
Brain Extracellular Fluid ◽  
Dc Potential ◽  
Arterial Plasma ◽  
Lumbar Cerebrospinal Fluid

In anesthetized, paralyzed dogs ventilated to maintain a normal PaCO2, metabolic alkalosis was induced and held constant over 6 h by infusion of sodium bicarbonate. Determination of pH, PCO2, (HCO3 minus), and (lactate) in cisternal and lumbar cerebrospinal fluid (CSF) and in arterial plasma together with measurement of the CSF/plasma DC potential differences permitted calculation of the electrochemical potential difference (mu) for H+ and HCO3 minus; measurements were made prior to induction of metabolic alkalosis at pHa equal to 7.40, as soon after induction as stable arterial values were achieved and 3, 4.5, and 6 h thereafter. A steady state for ion distribution was reached by 4.5 h. Values of mu for H+ and HCO3 minus returned to +0.1 and +0.9 mV of control at 6 h for cisternal CSF and +0.6 and minus 0.4 mV for lumbar CSF. This return of muH+ and muHCO3 minus close to control in the steady state is compatible with passive distribution of these ions between brain extracellular fluid and blood.

scholarly journals Comparison of serum, cerebrospinal fluid and brain extracellular fluid pharmacokinetics of lamotrigine

2000 ◽  
Vol 130 (2) ◽  
pp. 242-248 ◽  
Author(s):  
M C Walker ◽  
X Tong ◽  
H Perry ◽  
M S Alavijeh ◽  
P N Patsalos
Keyword(s):  
Cerebrospinal Fluid ◽  
Extracellular Fluid ◽  
Brain Extracellular Fluid

Changes in brain ECF pH during metabolic acidosis and alkalosis: a microelectrode study

1983 ◽  
Vol 55 (6) ◽  
pp. 1849-1853 ◽  
Author(s):  
S. Javaheri ◽  
A. De Hemptinne ◽  
B. Vanheel ◽  
I. Leusen
Keyword(s):  
Cerebrospinal Fluid ◽  
Metabolic Acidosis ◽  
Metabolic Alkalosis ◽  
Extracellular Fluid ◽  
Acid Base ◽  
Brain Extracellular Fluid ◽  
Group I ◽  
Venous Pco2 ◽  
Anesthetized Dogs ◽  
Acute Metabolic Acidosis

We used pH-sensitive double-barreled microelectrodes to measure brain extracellular fluid (ECF) pH in anesthetized dogs during isocapnic infusion acidosis (HCl) and alkalosis (Na2CO3) of 45-60 min duration. The diameter of the tips of these electrodes varied from less than 1 to 27 micron and were placed 5 mm below the surface of the parietal cortex. In group I (metabolic acidosis, n = 5) mean plasma and brain ECF pH fell significantly by 0.221 and 0.025, respectively, with changes in brain ECF pH being 11.3% of those noted in plasma. In group II (metabolic alkalosis, n = 5) mean plasma and brain ECF pH rose significantly by 0.170 and 0.049, respectively, with changes in brain ECF pH being 28.8% of those noted in plasma. Mean arterial and sagittal venous PCO2 and cisternal cerebrospinal fluid (CSF) acid-base variables did not change significantly during acid or base infusion. We conclude that during transients of isocapnic metabolic acid-base perturbations ionic gradients exist between brain ECF and CSF and that changes in brain ECF pH measured by microelectrodes follow the changes in plasma pH. These pH changes may play an important role in respiratory adaptations of acute metabolic acidosis and alkalosis.

scholarly journals Lumbar cerebrospinal fluid-to-brain extracellular fluid surrogacy is context-specific: insights from LeiCNS-PK3.0 simulations

2021 ◽  
Author(s):  
Mohammed A. A. Saleh ◽  
Chi Fong Loo ◽  
Jeroen Elassaiss-Schaap ◽  
Elizabeth C. M. De Lange
Keyword(s):  
Cerebrospinal Fluid ◽  
Drug Exposure ◽  
Specific Binding ◽  
Ph Effect ◽  
Extracellular Fluid ◽  
Csf Dynamics ◽  
Cns Diseases ◽  
Brain Extracellular Fluid ◽  
Drug Concentrations ◽  
Improved Model

AbstractPredicting brain pharmacokinetics is critical for central nervous system (CNS) drug development yet difficult due to ethical restrictions of human brain sampling. CNS pharmacokinetic (PK) profiles are often altered in CNS diseases due to disease-specific pathophysiology. We previously published a comprehensive CNS physiologically-based PK (PBPK) model that predicted the PK profiles of small drugs at brain and cerebrospinal fluid compartments. Here, we improved this model with brain non-specific binding and pH effect on drug ionization and passive transport. We refer to this improved model as Leiden CNS PBPK predictor V3.0 (LeiCNS-PK3.0). LeiCNS-PK3.0 predicted the unbound drug concentrations of brain ECF and CSF compartments in rats and humans with less than two-fold error. We then applied LeiCNS-PK3.0 to study the effect of altered cerebrospinal fluid (CSF) dynamics, CSF volume and flow, on brain extracellular fluid (ECF) pharmacokinetics. The effect of altered CSF dynamics was simulated using LeiCNS-PK3.0 for six drugs and the resulting drug exposure at brain ECF and lumbar CSF were compared. Simulation results showed that altered CSF dynamics changed the CSF PK profiles, but not the brain ECF profiles, irrespective of the drug’s physicochemical properties. Our analysis supports the notion that lumbar CSF drug concentration is not an accurate surrogate of brain ECF, particularly in CNS diseases. Systems approaches account for multiple levels of CNS complexity and are better suited to predict brain PK.

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