Hydrocephalus decreases chloride efflux from the choroid plexus epithelium

Knuckey, Neville W.; Preston, Jane E.; Palm, Donald E.; Epstein, Miran; Johanson, Conrad E.

doi:10.1016/0006-8993(93)91282-w

Cited by 27 publications

(15 citation statements)

References 18 publications

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“…Hence, studies of rodent choroid plexus transporters and CSF formation would seem highly relevant for human physiology as well. During hydrocephalus and brain edema, the CSF production by the choroid plexus is reduced, e.g., measured as decreased Cl Ϫ secretion (16). In a recent review, Weaver and colleagues (43) suggested that the net transport direction in hydrocephalus even may be reversed.…”

Section: Discussionmentioning

confidence: 99%

Distribution of sodium transporters and aquaporin-1 in the human choroid plexus

Prætorius

Nielsen

2006

American Journal of Physiology-Cell Physiology

135

121

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Section: Discussionmentioning

confidence: 99%

Distribution of sodium transporters and aquaporin-1 in the human choroid plexus

Prætorius

Nielsen

2006

American Journal of Physiology-Cell Physiology

135

121

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“…CL CSF may change because of brain disorders (30) and can be reduced using pharmacologic inhibitors (35)(36)(37)(38). The influence of CL CSF on AUC(C IAR ) and AUC(C IAR )/AUC(C IA ) predicted by our model is shown in Figure 4.…”

Section: Effect Of CL Csf On Therapeutic Ratiomentioning

confidence: 97%

A Pharmacokinetic Model for Radioimmunotherapy Delivered Through Cerebrospinal Fluid for the Treatment of Leptomeningeal Metastases

Lv¹,

Cheung²,

Fu³

2009

J Nucl Med

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Radioimmunotherapy can effectively treat leptomeningeal metastases when radiolabeled antibodies are administered into the cerebrospinal fluid (CSF). We developed a pharmacokinetic model to evaluate the role of kinetic and transport parameters of radioimmunotherapy in maximizing the therapeutic ratio, the ratio of the area under the curve for the concentration of the bound antibodies versus time (AUC[C IAR ]), to that for unbound antibodies (AUC[C IA ]). Methods: We simplified the CSF space as a single compartment and considered the binding of antibodies to antigens on tumor cells lining the surface of the CSF space. Mass conservation was applied to set up the equations for C IAR , C IA , and other pharmacokinetic variables. A RungeKutta method was used to solve the equations. Results: This model agreed with the measured data in 10 of 14 patients in the phase I trial of intra-Ommaya radioimmunotherapy using 131 I-3F8. Using this model, we predicted that increasing the affinity of antibodies to antigens greatly increases AUC(C IAR ) but not AUC(C IA ); for the same amount of isotope administered, the smaller antibody dose and the higher specific activity improves therapeutic ratio. When the isotope half-life (t 1/2-I ) was 0.77 h, increasing the antibody association constant enhanced AUC(C IAR ) much more than did decreasing the dissociation constant, even if overall affinity was unchanged. When t 1/2-I reached 240 h, decreasing the dissociation constant would slightly enhance AUC(C IAR ). Other predictions were that decreasing the CSF bulk flow rate would increase AUC(C IAR ), with 3 mL/h being optimal; at the same amount of antibody administered by continuous infusion and by split administrations, compared with that by the single bolus administration, one could improve AUC(C IAR ) by up to 1.8-and 1.7-fold, respectively; and for an antibody affinity of 10 28 M, increasing t 1/2-I from 0.77 up to 64 h could greatly enhance the therapeutic ratio. Conclusion: The strong agreement between model predictions and patient data supports the validity of the assumptions and simplifications in our model. The predictions using this model are not intuitive and need to be validated in future clinical trials. The improved therapeutic ratio by optimized kinetic and transport parameters may enhance the clinical efficacy of this new treatment modality.

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“…Results demonstrated a decrease in the ability of the CP to release chloride following hydrocephalus. This decrease in chloride efflux might reflect a decrease in the water movement by the epithelial cells and hence a decrease in CSF formation [63]. The authors further suggested that decreased function of the CP epithelium might result from neuronal or hormonal regulation of the CP in response to raised ICP [63].…”

Section: Changes In the Secretory Process Of The Choroid Plexusmentioning

confidence: 97%

“…With regard to hydrocephalus, Knuckey et al, [63] studied the function of the CP in rats exposed to increased ICP. Results demonstrated a decrease in the ability of the CP to release chloride following hydrocephalus.…”

Section: Changes In the Secretory Process Of The Choroid Plexusmentioning

confidence: 99%

The Valsalva Maneuver and Alzheimers Disease: Is there a link?

Wostyn

Audenaert²,

Deyn

2009

CAR

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Recent research findings provide evidence for Alzheimer's disease-related changes in brain diseases, such as normal pressure hydrocephalus and traumatic brain injury, and in glaucoma at the level of the retinal ganglion cells. This is a group of diseases that affect central nervous system tissue and are characterized by elevation of intracranial or intraocular pressure and/or local shear stress and strain. This strengthens the possibility that Alzheimer-type changes in these diseases may result at least in part from exposure of central nervous system tissue to elevated mechanical load. As activities or diseases with significant Valsalva effort can generate increased intracranial pressures, we hypothesize that individuals who frequently perform strong Valsalva maneuvers (e.g., long hours of repetitive heavy lifting, sequences of blows during the playing of a wind instrument, forceful and repetitive cough, bearing-down efforts during parturition) may be more susceptible to developing Alzheimer's disease. In this paper, we discuss three hypotheses about the mechanisms by which extensive use of the Valsalva maneuver might contribute to the neuropathogenesis of Alzheimer's disease: via mechanical stress-induced events in the hippocampus and/or via changes in the secretory process of the choroid plexus and/or via hemodynamic changes in cerebral blood flow. If confirmed, this hypothesis could have implications in clinical practice.

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Hydrocephalus decreases chloride efflux from the choroid plexus epithelium

Cited by 27 publications

References 18 publications

Distribution of sodium transporters and aquaporin-1 in the human choroid plexus

Distribution of sodium transporters and aquaporin-1 in the human choroid plexus

A Pharmacokinetic Model for Radioimmunotherapy Delivered Through Cerebrospinal Fluid for the Treatment of Leptomeningeal Metastases

The Valsalva Maneuver and Alzheimers Disease: Is there a link?

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