Regulation of cerebrospinal fluid bicarbonate by the cat choroid plexus.

Husted, Russell F.; Reed, Donal J.

doi:10.1113/jphysiol.1977.sp011820

Cited by 45 publications

(28 citation statements)

References 40 publications

(46 reference statements)

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“…CSF is continuously being produced and eliminated at a rate of 500 ml per day in healthy human adults, with a total volume of 135 ml at any one time. An array of transporters and channels line the basolateral and apical membranes of the choroid plexus epithelium at the lateral ventricles, facilitating the net transfer of ions, including Na ϩ , Cl Ϫ , K ϩ , and HCO 3 Ϫ , into CSF (4,9,24,29). Furthermore, the CSF not only carries polypeptides that pass through the blood-brain barrier but also harbors neuro-peptides and proteins manufactured locally as a recipient of cell-shedding products from the brain and the 7.…”

Section: Discussionmentioning

confidence: 99%

Survival Defects of Cryptococcus neoformans Mutants Exposed to Human Cerebrospinal Fluid Result in Attenuated Virulence in an Experimental Model of Meningitis

Lee¹,

Toffaletti²,

Tenor³

et al. 2010

Infect Immun

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Cryptococcus neoformans is a fungal pathogen that encounters various microenvironments during growth in the mammalian host, including intracellular vacuoles, blood, and cerebrospinal fluid (CSF). Because the CSF is isolated by the blood-brain barrier, we hypothesize that CSF presents unique stresses that C. neoformans must overcome to establish an infection. We assayed 1,201 mutants for survival defects in growth media, saline, and human CSF. We assessed CSF-specific mutants for (i) mutant survival in both human bronchoalveolar lavage (BAL) fluid and fetal bovine serum (FBS), (ii) survival in macrophages, and (iii) virulence using both Caenorhabditis elegans and rabbit models of cryptococcosis. Thirteen mutants exhibited significant survival defects unique to CSF. The mutations of three of these mutants were recreated in the clinical serotype A strain H99: deletions of the genes for a cation ATPase transporter (ena1⌬), a putative NEDD8 ubiquitin-like protein (rub1⌬), and a phosphatidylinositol 4-kinase (pik1⌬). Mutant survival rates in yeast media, saline, and BAL fluid were similar to those of the wild type; however, survival in FBS was reduced but not to the levels in CSF. These mutant strains also exhibited decreased intracellular survival in macrophages, various degrees of virulence in nematodes, and severe attenuation of survival in a rabbit meningitis model. We analyzed the CSF by mass spectrometry for candidate compounds responsible for the survival defect. Our findings indicate that the genes required for C. neoformans survival in CSF ex vivo are necessary for survival and infection in this unique host environment.

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Section: Discussionmentioning

confidence: 99%

Survival Defects of Cryptococcus neoformans Mutants Exposed to Human Cerebrospinal Fluid Result in Attenuated Virulence in an Experimental Model of Meningitis

Lee¹,

Toffaletti²,

Tenor³

et al. 2010

Infect Immun

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“…Consistent with this fact, there is evidence that NKCC1 mediates both outward-directed (into the CSF lumen) and inward-directed ion transport. 75,107,147 Because the ion composition of CSF is tightly regulated and maintained, 58,94,114 the bidirectional ion movement via NKCC1 might enable it to respond dynamically to physiological changes in the CSF to maintain homeostasis. In other secretory epithelia, the Ste20/SPS1-related proline-alanine-rich protein kinase (SPAK) associates with NKCC1 via a CCT-binding module in SPAK and a (R/K)FX(V/I)-binding motif in NKCC1 105 and stimulates NKCC1 via direct phosphorylation at Thr-203/Thr-207/Thr-212.…”

mentioning

confidence: 99%

Cerebrospinal fluid hypersecretion in pediatric hydrocephalus

Karimy¹,

Durán²,

Hu³

et al. 2016

FOC

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Hydrocephalus, despite its heterogeneous causes, is ultimately a disease of disordered CSF homeostasis that results in pathological expansion of the cerebral ventricles. Our current understanding of the pathophysiology of hydrocephalus is inadequate but evolving. Over this past century, the majority of hydrocephalus cases has been explained by functional or anatomical obstructions to bulk CSF flow. More recently, hydrodynamic models of hydrocephalus have emphasized the role of abnormal intracranial pulsations in disease pathogenesis. Here, the authors review the molecular mechanisms of CSF secretion by the choroid plexus epithelium, the most efficient and actively secreting epithelium in the human body, and provide experimental and clinical evidence for the role of increased CSF production in hydrocephalus. Although the choroid plexus epithelium might have only an indirect influence on the pathogenesis of many types of pediatric hydrocephalus, the ability to modify CSF secretion with drugs newer than acetazolamide or furosemide would be an invaluable component of future therapies to alleviate permanent shunt dependence. Investigation into the human genetics of developmental hydrocephalus and choroid plexus hyperplasia, and the molecular physiology of the ion channels and transporters responsible for CSF secretion, might yield novel targets that could be exploited for pharmacotherapeutic intervention.

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“…Thus, the large-cavity CSF reservoir is a ''buffer medium'' to accommodate brain ''spillovers.'' By volume dilution, and active transport by plexus to remove K from CSF or neutralize H by secretion of HCO 3 (18), there is minimal fluctuation of extracellular ions. CSF [K] is buffered by the Na-K pump and NaK2Cl transporters (19) in the apical membrane of CP epithelium.…”

Section: Buffering Reservoir: Biochemical and Biophysicalmentioning

confidence: 99%

Choroid Plexus–Cerebrospinal Fluid Circulatory Dynamics: Impact on Brain Growth, Metabolism, and Repair

Johanson

2008

Neuroscience in Medicine

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Regulation of cerebrospinal fluid bicarbonate by the cat choroid plexus.

Cited by 45 publications

References 40 publications

Survival Defects of Cryptococcus neoformans Mutants Exposed to Human Cerebrospinal Fluid Result in Attenuated Virulence in an Experimental Model of Meningitis

Survival Defects of Cryptococcus neoformans Mutants Exposed to Human Cerebrospinal Fluid Result in Attenuated Virulence in an Experimental Model of Meningitis

Cerebrospinal fluid hypersecretion in pediatric hydrocephalus

Choroid Plexus–Cerebrospinal Fluid Circulatory Dynamics: Impact on Brain Growth, Metabolism, and Repair

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