Aquaporins: relevance to cerebrospinal fluid physiology and therapeutic potential in hydrocephalus

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

ABSTRACT 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.

  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: This study was designed to evaluate the neuroprotective effects of Morinda citrifolia L. (Rubiaceae), commonly known as noni, and memantine (a N-methy-D-aspartate receptor inhibitor) on hydrocephalus-induced neurodegenerative disorders. Kaolin was injected into the cistern magna of male adult New Zealand rabbits to establish a hydrocephalus animal model. Memantine (20 mg/kg, intraperitoneally; memantine-treated group) or noni (5 mL/kg, intragastrically; noni-treated group) was administered daily for 2 weeks. Microtubule-associated protein-2 and caspase-3 immunohistochemistry were performed to detect neuronal degeneration and apoptosis in the periventricular tissue of the fourth ventricle of rabbits. Microtubule-associated protein-2 staining density was significantly decreased in the hydrocephalic group, while the staining density was significantly increased in the memantine- and noni-treated groups, especially in the noni-treated group. Noni treatment decreased the number of caspase-3-positive cells in rabbits with hydrocephalus, while memantine had no effect. These findings suggest that noni exhibits more obvious inhibitory effects on hydrocephalus-induced neurodegenerative disorders than memantine in periventricular tissue of the fourth ventricle.
    Neural Regeneration Research 03/2013; 8(9):773-82. DOI:10.3969/j.issn.1673-5374.2013.09.001 · 0.23 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The cerebrospinal fluid (CSF) is contained in the brain ventricles and the cranial and spinal subarachnoid spaces. The mean CSF volume is 150 ml, with 25 ml in the ventricles and 125 ml in subarachnoid spaces. CSF is predominantly, but not exclusively, secreted by the choroid plexuses. Brain interstitial fluid, ependyma and capillaries may also play a poorly defined role in CSF secretion. CSF circulation from sites of secretion to sites of absorption largely depends on the arterial pulse wave. Additional factors such as respiratory waves, the subject's posture, jugular venous pressure and physical effort also modulate CSF flow dynamics and pressure. Cranial and spinal arachnoid villi have been considered for a long time to be the predominant sites of CSF absorption into the venous outflow system. Experimental data suggest that cranial and spinal nerve sheaths, the cribriform plate and the adventitia of cerebral arteries constitute substantial pathways of CSF drainage into the lymphatic outflow system. CSF is renewed about four times every 24 hours. Reduction of the CSF turnover rate during ageing leads to accumulation of catabolites in the brain and CSF that are also observed in certain neurodegenerative diseases. The CSF space is a dynamic pressure system. CSF pressure determines intracranial pressure with physiological values ranging between 3 and 4 mmHg before the age of one year, and between 10 and 15 mmHg in adults. Apart from its function of hydromechanical protection of the central nervous system, CSF also plays a prominent role in brain development and regulation of brain interstitial fluid homeostasis, which influences neuronal functioning.
    European Annals of Otorhinolaryngology, Head and Neck Diseases 11/2011; 128(6):309-16. DOI:10.1016/j.anorl.2011.03.002
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: BACKGROUND: Hydrocephalus is a central nervous system (CNS) disorder characterized by the abnormalaccumulation of cerebrospinal fluid (CSF) in cerebral ventricles, resulting their dilatation andassociated brain tissue injury. The pathogenesis of hydrocephalus remains unclear; however,recent reports suggest the possible involvement of abnormal osmotic gradients. Here weexplore the kinetics associated with manipulating CSF osmolarity on ventricle volume (VV)in the normal rat brain. METHODS: CSF was made hyper-osmotic by introducing 10KD dextran into the lateral ventricle, eitherby acute injection at different concentrations or by chronic infusion at a single concentration.The induction and withdrawal kinetics of dextran infusion on VV were explored in bothcontexts. RESULTS: Acute intraventricular injection of dextran caused a rapid increase in VV which completelyreversed within 24 hours. These kinetics are seemingly independent of the CSF osmolarity across a range spanning an order of magnitude; however, the magnitude of the transientincrease in VV was proportional to CSF osmolarity. By contrast, continuous intraventricularinfusion of dextran at a relatively low concentration caused a more gradual increase in VVwhich was very slow to reverse when infusion was suspended after five days. CONCLUSION: We conclude that hyperosmolar CSF is sufficient to produce a proportional degree ofhydrocephalus in the normal rat brain, and that this phenomenon exhibits hysteresis if CSFhyperosmolarity is persistent. Thus pathologically-induced increases in CSF osmolarity maybe similarly associated with certain forms of clinical hydrocephalus. An improvedunderstanding of this phenomenon and its kinetics may facilitate the development of noveltherapies for the treatment of clinical hydrocephalus.
    07/2012; 9(1):13. DOI:10.1186/2045-8118-9-13

Preview (3 Sources)

Available from