Aquaporins: relevance to cerebrospinal fluid physiology and therapeutic potential in hydrocephalus. Cerebrospinal Fluid Res 7:15

Kids Neurosurgical Research Unit, Institute of Neuroscience and Muscle Research, Kids Research Institute, Children's Hospital at Westmead, Hawkesbury Rd, Westmead NSW 2145, Australia. .
Cerebrospinal Fluid Research (Impact Factor: 1.81). 09/2010; 7:15. DOI: 10.1186/1743-8454-7-15
Source: PubMed


The discovery of a family of membrane water channel proteins called aquaporins, and the finding that aquaporin 1 was located in the choroid plexus, has prompted interest in the role of aquaporins in cerebrospinal fluid (CSF) production and consequently hydrocephalus. While the role of aquaporin 1 in choroidal CSF production has been demonstrated, the relevance of aquaporin 1 to the pathophysiology of hydrocephalus remains debated. This has been further hampered by the lack of a non-toxic specific pharmacological blocking agent for aquaporin 1. In recent times aquaporin 4, the most abundant aquaporin within the brain itself, which has also been shown to have a role in brain water physiology and relevance to brain oedema in trauma and tumours, has become an alternative focus of attention for hydrocephalus research. This review summarises current knowledge and concepts in relation to aquaporins, specifically aquaporin 1 and 4, and hydrocephalus. It also examines the relevance of aquaporins as potential therapeutic targets in hydrocephalus and other CSF circulation disorders.

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    • "It is worth to note that acetazolamide is also part of arylsulphonamide family. Although its potential effects on AQPs are still debated (72), recent studies have shown an interaction with AQP1, both in vitro (73) and in vivo (74), and a possible reversible inhibition of AQP4 (75). "
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    ABSTRACT: Cerebrospinal fluid (CSF) overproduction results from either CSF infection or choroid plexus hypertrophy or tumor, with only a single idiopathic case described so far. We report a unique case of a male infant with Crouzon syndrome who presented with intracranial hypertension, caused by up to 4-fold increase in CSF daily production. Conditions related to CSF overproduction, namely central nervous system infections and choroid plexus hypertrophy or tumor, were ruled out by repeated magnetic resonance imaging and CSF samples. Medical therapy failed to reduce CSF production and the patient underwent several shunting procedures, cranial expansion, and endoscopic coagulation of the choroid plexus. This article thoroughly reviews pertinent literature on CSF production mechanisms and possible therapeutic implications.
    Croatian Medical Journal 08/2014; 55(4):377-87. DOI:10.3325/cmj.2014.55.377 · 1.31 Impact Factor
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    • "There is a K+/Cl- cotransporter, but its role is not yet well understood [96]. The molecular mechanisms of choroidal CSF production are comprehensively reviewed in [96,105,106]. "
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    ABSTRACT: According to the traditional understanding of cerebrospinal fluid (CSF) physiology, the majority of CSF is produced by the choroid plexus, circulates through the ventricles, the cisterns, and the subarachnoid space to be absorbed into the blood by the arachnoid villi. This review surveys key developments leading to the traditional concept. Challenging this concept are novel insights utilizing molecular and cellular biology as well as neuroimaging, which indicate that CSF physiology may be much more complex than previously believed. The CSF circulation comprises not only a directed flow of CSF, but in addition a pulsatile to and fro movement throughout the entire brain with local fluid exchange between blood, interstitial fluid, and CSF. Astrocytes, aquaporins, and other membrane transporters are key elements in brain water and CSF homeostasis. A continuous bidirectional fluid exchange at the blood brain barrier produces flow rates, which exceed the choroidal CSF production rate by far. The CSF circulation around blood vessels penetrating from the subarachnoid space into the Virchow Robin spaces provides both a drainage pathway for the clearance of waste molecules from the brain and a site for the interaction of the systemic immune system with that of the brain. Important physiological functions, for example the regeneration of the brain during sleep, may depend on CSF circulation.
    Fluids and Barriers of the CNS 05/2014; 11(1):10. DOI:10.1186/2045-8118-11-10
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    • "Aquaporin (AQP1/3/4) channels on CSF-facing membrane mediate water flux into ventricles [105]. Polarized distribution of carbonic anhydrase (CAR) and Na+/K+-ATPase, and aquaporins, enable net ion and water translocation to CSF (see [104], [106] for review). The gene Slc4a7 (NBCn1) was not detected by RNA-Seq, although it has been reported in both rat and mouse choroid plexus [107]); this may have been for technical reasons or because of lack of antibody specificity see section “Limitations of study”. "
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    ABSTRACT: We provide comprehensive identification of embryonic (E15) and adult rat lateral ventricular choroid plexus transcriptome, with focus on junction-associated proteins, ionic influx transporters and channels. Additionally, these data are related to new structural and previously published permeability studies. Results reveal that most genes associated with intercellular junctions are expressed at similar levels at both ages. In total, 32 molecules known to be associated with brain barrier interfaces were identified. Nine claudins showed unaltered expression, while two claudins (6 and 8) were expressed at higher levels in the embryo. Expression levels for most cytoplasmic/regulatory adaptors (10 of 12) were similar at the two ages. A few junctional genes displayed lower expression in embryos, including 5 claudins, occludin and one junctional adhesion molecule. Three gap junction genes were enriched in the embryo. The functional effectiveness of these junctions was assessed using blood-delivered water-soluble tracers at both the light and electron microscopic level: embryo and adult junctions halted movement of both 286Da and 3kDa molecules into the cerebrospinal fluid (CSF). The molecular identities of many ion channel and transporter genes previously reported as important for CSF formation and secretion in the adult were demonstrated in the embryonic choroid plexus (and validated with immunohistochemistry of protein products), but with some major age-related differences in expression. In addition, a large number of previously unidentified ion channel and transporter genes were identified for the first time in plexus epithelium. These results, in addition to data obtained from electron microscopical and physiological permeability experiments in immature brains, indicate that exchange between blood and CSF is mainly transcellular, as well-formed tight junctions restrict movement of small water-soluble molecules from early in development. These data strongly indicate the brain develops within a well-protected internal environment and the exchange between the blood, brain and CSF is transcellular and not through incomplete barriers.
    PLoS ONE 07/2013; 8(7):e65629. DOI:10.1371/journal.pone.0065629 · 3.23 Impact Factor
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