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At least 19 recordsLinked to original sources
PubMed1990

Morphological estimation of brain extracellular fluid dynamics in cold-induced edema from the aspect of cerebrospinal fluid-extracellular fluid communication.

Following the induction of cold injury in the parietal cortex of rats, the brain extracellular fluid dynamics under conditions of cryogenic edema were investigated morphologically from the aspect of extracellular fluid (ECF)-cerebrospinal fluid (CSF) communication using horseradish peroxidase (HRP) injected into the cisterna magna as a marker. About 24 h after the induction of cold injury, HRP was distributed in the subjacent white matter of the lesion and around the ventricle. Forty-eight hours after injury, the distribution of HRP around the lesion became distinctive. This distribution of HRP became more concentrated at the same location on day 3-4 after injury. At this time, HRP was observed to be distributed along the walls of small vessels, in the cytoplasm of a few neurons and in the neuropil around the lesion by light microscopy. At small vessels around the lesion, a dense deposit of HRP at the basement membrane and many abluminal vesicles were evident by electron microscopy. These findings indicate that ECF-CSF communication changes drastically under the influence of edema fluid dynamics. In particular, the dense distribution of HRP around the lesion on day 3-4 after injury can be attributed to active retrograde transport by vessels in this area, a phenomenon considered important for edema resolution.

Animals↗
PubMed1985

Cerebrospinal fluid and extracellular fluid: their relationship to pressure and duration of canine hydrocephalus.

Fifteen greyhound dogs were made hydrocephalic by the transsphenoidal injection of silicone into the basal cisterns at the level of the tentorial incisura. Six of these animals had ventriculocisternal perfusions 4 weeks later and six at 8 weeks, half at 150 and half at 100 mm H2O. Three 12-week dogs were perfused at 150 mm H2O. Serial sections of brain from the ependyma of the left frontal horn to the overlying pia were counted for 14C inulin and 3H methotrexate uptake. Tissue concentrations of both markers varied indirectly with distance from ependyma and from pia, and varied directly with perfusion pressure. The data indicate that the diffusional pathway between cerebrospinal fluid (CSF) and extracellular fluid (ECF) can be modified by CSF pressure changes, i.e., CSF flows from the ventricles and subarachnoid space into the extracellular space when CSF pressures are raised. Brain uptake of inulin and methotrexate was significantly increased in the dogs made hydrocephalic 4 weeks prior to perfusion, but was less so in the 8-week hydrocephalics. Uptake of the tracers in three 12-week animals was similar to that found previously in normal dogs at elevated pressures. These findings correspond in location and time to the periventricular lucencies that are seen by computed tomography in human subacute hydrocephalus. They are apparently due to pressure-related changes in the volume of the ECF.

Animals↗
PubMed1999

Estimation of topiramate in subdural cerebrospinal fluid, subcutaneous extracellular fluid, and plasma: a single case microdialysis study.

PURPOSE: To estimate topiramate (TPM) concentrations in subdural cerebrospinal fluid (CSF), subcutaneous extracellular fluid (ECF), and plasma and to study the correlation of TPM concentrations in these three different compartments. METHODS: In this single case study of a patient with drug-resistant partial epilepsy undergoing presurgical evaluation with subdural EEG monitoring, we used microdialysis to estimate concentrations of unbound TPM in CSF of the subdural space and ECF of abdominal subcutaneous tissue. Blood samples were drawn for estimation of TPM concentrations in plasma. RESULTS: The correlation between unbound TPM concentrations in subdural CSF and abdominal subcutaneous ECF was good. The mean ratio of ECF/CSF TPM concentration was 0.93 (SD+/-0.03) and the correlation coefficient was 0.98. The mean ratio of ECF/total plasma TPM was 0.75 (SD+/-0.06), and the correlation coefficient was 0.99. The mean ratio of CSF/total plasma TPM was 0.81 (SD+/-0.06), and the correlation coefficient was 0.97. CONCLUSIONS: Assuming a protein binding of TPM of approximately 13%. it is concluded that, based on nine microdialysis samples from a single subject, TPM levels in the CSF at the cortical surface are approximately the same as the unbound plasma levels. Additional patients should be studied to confirm the results.

Adult↗
PubMed2001

Distribution of valproate to subdural cerebrospinal fluid, subcutaneous extracellular fluid, and plasma in humans: a microdialysis study.

We sought to study the time course of the distribution of valproate (VPA) to subdural cerebrospinal fluid (CSF) in relation to subcutaneous extracellular fluid (ECF) and plasma after a single oral dose and to study the distribution to these three compartments under steady-state conditions. Microdialysis was used to estimate unbound VPA concentrations in subdural CSF and subcutaneous ECF, and blood samples were drawn for estimation of total and unbound VPA plasma concentrations in four patients with drug-resistant partial epilepsy undergoing presurgical evaluation with subdural EEG monitoring. Three patients were given a single oral dose of VPA, and one patient was receiving regular VPA treatment. VPA was analyzed by gas chromatography with flame ionization detection. The distribution of VPA to subdural CSF was rapid (Tmax, 3.5 h in two patients and 5.5 h in one patient) and subject to a minor delay in all three patients compared with that in the subcutaneous tissue ECF (Tmax, 2.5 h in all three patients), which in turn exhibited no evidence of a distribution delay compared with plasma. Subdural CSF levels of VPA were slightly lower than subcutaneous ECF levels (mean ratio, 0.78) and unbound plasma levels (mean ratio, 0.91). VPA rapidly enters the subdural CSF in unbound concentrations marginally lower than those obtained in subcutaneous ECF and plasma. These findings provide a pharmacokinetic rationale for acute administration of VPA. The good correlation between VPA concentrations in subcutaneous ECF and subdural CSF indicates that estimation of unbound VPA concentrations in subcutaneous tissue using microdialysis sampling has the potential to be useful for monitoring purposes.

Administration, Oral↗
PubMed2000

Influence of ovariectomy on extracellular fluid volume in rats: assessment of extracellular fluid volume by means of bromide.

There is considerable evidence that the extracellular fluid volume (ECV) may change in disease states or during longitudinal Intervention studies. Therefore, the measurement of ECV is Important for studying body composition in patients and laboratory animals. We present a modified plasma bromide (Br-, non-radioactive) assay using anion-exchange chromatography, in which a small blood sample of 200 microL (100 microL of plasma) appeared to be enough to reproducibly measure ECV. The inter- and intra-assay accuracy of the Br- analysis ranged from -1.6% to 0.9% and from -0.5% to 0%, respectively. The inter- and intra-assay precision ranged from 1.3% to 1.7% and from 0.6% to 1.2%, respectively. This modified precise and accurate Br- analysis in a small blood sample was applied to investigate whether the ECV changed in rats after ovariectomy. Ovariectomy significantly (P < .05) reduced the ECV as compared with results in SHAM rats. This observation indicates that a change in clinical condition may change ECV, which has consequences for the determination of, for example, the fractional absorption and the relative bioavailability of compounds principally distributed through the ECV.

Animals↗
PubMed2000

Comparison of serum, cerebrospinal fluid and brain extracellular fluid pharmacokinetics of lamotrigine.

We investigated the rate of penetration into and the intra-relationship between the serum, cerebrospinal fluid (CSF) and regional brain extracellular fluid (bECF) compartments following systemic administration of lamotrigine in rat. The serum pharmacokinetics were biphasic with an initial distribution phase, (half-life approximately 3 h), and then a prolonged elimination phase of over 30 h. The serum pharmacokinetics were linear over the range 10 - 40 mg kg(-1). Using direct sampling of CSF with concomitant serum sampling, the calculated penetration half-time into CSF was 0.42+/-0.15 h. At equilibrium, the CSF to total serum concentration ratio (0.61+/-0.02) was greater than the free to total serum concentration (0.39+/-0.01). Using in vivo recovery corrected microdialysis sampling in frontal cortex and hippocampus with concomitant serum sampling, the calculated penetration half-time of lamotrigine into bECF, 0.51+/-0.11 h, was similar to that for CSF and was not area or dose dependent. At equilibrium, the bECF to total serum concentration ratio (0.40+/-0.04) was similar to the free to total serum concentration (0.39+/-0.01), and did not differ between hippocampus and frontal cortex. The species specific serum kinetics can explain the prolonged action of lamotrigine in rat seizure models. Lamotrigine has a relatively slow penetration into both CSF and bECF compartments compared with antiepileptic drugs used in acute seizures. Furthermore, the free serum drug concentration is not the sole contributor to the CSF compartment, and the CSF concentration is an overestimate of the bECF concentration of lamotrigine.

Animals↗
PubMed2004

From artificial cerebro-spinal fluid (aCSF) to artificial extracellular fluid (aECF): microdialysis perfusate composition effects on in vivo brain ECF glucose measurements.

Microdialysis (mD) is the predominant technique for measurements of brain chemistry, especially when such measurements are made in awake animals. Relatively little attention has been paid, however, to the potential effect on such measurements of variation in the perfusate solution used. Here, we report that small variations in the ionic composition of microdialysis perfusate produced four-fold differences (0.53-2.18 mM) in the results obtained when measuring brain extracellular fluid (ECF) glucose. These changes may be linked to concomitant alterations of local neural activity caused by the perfusate composition. In addition to perfusate composition, probe type also proved to have a significant impact on microdialysis measurements. Further, we report the first direct microdialysis measurements of brain ECF ionic composition, showing significant differences from that of the cerebro-spinal fluid (CSF). Modifying the ionic composition of microdialysis perfusate based on these measurements resulted in a measured hippocampal ECF glucose level of 1.26 +/- .04 mM. Increased understanding of the impact of differences in the perfusate solutions used by different laboratories may provide a basis for reconciliation of apparently disparate microdialysis results within the literature.

Animals↗
PubMed1985

Increased digitalis-like activity in human cerebrospinal fluid after expansion of the extracellular fluid volume.

The present study was designed to determine whether acute expansion of the extracellular fluid volume influenced the digitalis-like activity of human cerebrospinal fluid (CSF), previously described by our laboratory. Human CSF samples, drawn before and 30 minutes after the intravenous infusion of 1 liter of either saline or glucose solutions, were assayed for digitalis-like activity by inhibition of either the 86Rb+ uptake into human erythrocytes or by the activity of a purified Na+ - K+ ATPase. The CSF inhibitory activity on both systems significantly increased after the infusion of sodium solutions but did not change after the infusion of glucose. These results indicate that the digitalis-like factor of human CSF might be involved in the regulation of the extracellular fluid volume and electrolyte content and thereby in some of the physiological responses to sodium loading.

Calcium↗
PubMed1983

Effects of isotonic fluid load on plasma water and extracellular fluid volumes in the rat.

An isotonic fluid load was given to rats by infusing 12 ml saline i.v. in 60 min. The plasma water and extracellular fluid volumes of the whole animal and selected tissues were subsequently studied with 125I human serum albumin and 51Cr EDTA. The fluid infused was equivalent to 130% of the plasma water volume. The total extracellular fluid volume increased by 17%, while the total plasma water measured with RIHSA remained unchanged. The regional extracellular fluid volumes increased in the lung (14%), the gastric fundus (15%), large intestine (21%) and skin (28%). The results illustrate the selective distribution of an isotonic fluid overload, those tissues being effected having high compliances.

Animals↗