Aquaporin and brain diseases.

BACKGROUND The presence of water channel proteins, aquaporins (AQPs), in the brain led to intense research in understanding the underlying roles of each of them under normal conditions and pathological conditions. SCOPE OF REVIEW In this review, we summarize some of the recent knowledge on the 3 main AQPs (AQP1, AQP4 and AQP9), with a special focus on AQP4, the most abundant AQP in the central nervous system. MAJOR CONCLUSIONS AQP4 was most studied in several brain pathological conditions ranging from acute brain injuries (stroke, traumatic brain injury) to the chronic brain disease with autoimmune neurodegenerative diseases. To date, no specific therapeutic agents have been developed to either inhibit or enhance water flux through these channels. However, experimental results strongly underline the importance of this topic for future investigation. Early inhibition of water channels may have positive effects in prevention of edema formation in brain injuries but at later time points during the course of a disease, AQP is critical for clearance of water from the brain into blood vessels. GENERAL SIGNIFICANCE Thus, AQPs, and in particular AQP4, have important roles both in the formation and resolution of edema after brain injury. The dual, complex function of these water channel proteins makes them an excellent therapeutic target. This article is part of a Special Issue entitled Aquaporins.

[1]  A S Verkman,et al.  Three distinct roles of aquaporin-4 in brain function revealed by knockout mice. , 2006, Biochimica et biophysica acta.

[2]  D. Ribatti,et al.  Role of aquaporins in cell migration and edema formation in human brain tumors. , 2011, Experimental cell research.

[3]  M. Cahalan,et al.  Chloride channels activated by osmotic stress in T lymphocytes , 1993, The Journal of general physiology.

[4]  A. Warth,et al.  Redistribution of aquaporin-4 in human glioblastoma correlates with loss of agrin immunoreactivity from brain capillary basal laminae , 2004, Acta Neuropathologica.

[5]  K. Davidson,et al.  Freeze-fracture and immunogold analysis of aquaporin-4 (AQP4) square arrays, with models of AQP4 lattice assembly , 2004, Neuroscience.

[6]  A. Nehlig,et al.  Hypervascularization in the Magnocellular Nuclei of the Rat Hypothalamus: Relationship with the Distribution of Aquaporin‐4 and Markers of Energy Metabolism , 2000, Journal of neuroendocrinology.

[7]  Jacqueline Palace,et al.  Myasthenia gravis and neuromyelitis optica spectrum disorder , 2012, Neurology.

[8]  Darrin J. Lee,et al.  Laminar-specific and developmental expression of aquaporin-4 in the mouse hippocampus , 2011, Neuroscience.

[9]  U. Heinemann,et al.  Involvement of Stretch-Activated Cl− Channels in Ramification of Murine Microglia , 1998, The Journal of Neuroscience.

[10]  A. Verkman,et al.  The Journal of Experimental Medicine CORRESPONDENCE , 2005 .

[11]  J. Garvin,et al.  Aquaporins as gas channels , 2011, Pflügers Archiv - European Journal of Physiology.

[12]  M. Papadopoulos,et al.  Aquaporin 4 and neuromyelitis optica , 2012, The Lancet Neurology.

[13]  T. Tatlisumak,et al.  The blood–brain barrier is continuously open for several weeks following transient focal cerebral ischemia , 2008, Neuroscience.

[14]  J. Badaut,et al.  Early Brain Injury Alters the Blood–Brain Barrier Phenotype in Parallel with β-Amyloid and Cognitive Changes in Adulthood , 2013, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[15]  Geoffrey T Manley,et al.  Increased seizure duration and slowed potassium kinetics in mice lacking aquaporin‐4 water channels , 2006, Glia.

[16]  S. Cisternino,et al.  Heterogeneity in the Rat Brain Vasculature Revealed by Quantitative Confocal Analysis of Endothelial Barrier Antigen and P-Glycoprotein Expression , 2012, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[17]  Patrick Poulet,et al.  Astrocytic hypertrophy in dysmyelination influences the diffusion anisotropy of white matter , 2007, Journal of neuroscience research.

[18]  C. Moonen,et al.  Differential aquaporin 4 expression during edema build-up and resolution phases of brain inflammation , 2011, Journal of Neuroinflammation.

[19]  D. Loane,et al.  Role of microglia in neurotrauma , 2010, Neurotherapeutics.

[20]  Geoffrey T. Manley,et al.  Involvement of aquaporin-4 in astroglial cell migration and glial scar formation , 2005, Journal of Cell Science.

[21]  Klaus Schulten,et al.  Mechanism of gating and ion conductivity of a possible tetrameric pore in aquaporin-1. , 2006, Structure.

[22]  Jian-Guo Chen,et al.  Aquaporin-4 Deficiency Impairs Synaptic Plasticity and Associative Fear Memory in the Lateral Amygdala: Involvement of Downregulation of Glutamate Transporter-1 Expression , 2012, Neuropsychopharmacology.

[23]  W. Arruda,et al.  NMO-IgG positive neuromyelitis optica in a patient with myasthenia gravis but no thymectomy , 2008, Journal of the Neurological Sciences.

[24]  K. Kiening,et al.  Decreased hemispheric Aquaporin-4 is linked to evolving brain edema following controlled cortical impact injury in rats , 2002, Neuroscience Letters.

[25]  M. Etemadifar,et al.  Myasthenia Gravis during the Course of Neuromyelitis Optica , 2011, Case Reports in Neurology.

[26]  C. Hulsebosch,et al.  Acute and chronic changes in aquaporin 4 expression after spinal cord injury , 2006, Neuroscience.

[27]  J. Rafols,et al.  The role of hypoxia-inducible factor-1α, aquaporin-4, and matrix metalloproteinase-9 in blood-brain barrier disruption and brain edema after traumatic brain injury. , 2011, Journal of neurosurgery.

[28]  J. Bloch,et al.  Cell locations for AQP1, AQP4 and 9 in the non-human primate brain , 2010, Neuroscience.

[29]  Nicolas Singewald,et al.  The Modulatory Role of the Lateral Septum on Neuroendocrine and Behavioral Stress Responses , 2010, Neuropsychopharmacology.

[30]  G. E. Vates,et al.  A Paravascular Pathway Facilitates CSF Flow Through the Brain Parenchyma and the Clearance of Interstitial Solutes, Including Amyloid β , 2012, Science Translational Medicine.

[31]  G. Manley,et al.  Greatly impaired migration of implanted aquaporin‐4‐deficient astroglial cells in mouse brain toward a site of injury , 2007, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[32]  C. Honey,et al.  Regulation of aquaporin-4 in a traumatic brain injury model in rats. , 2003, Journal of neurosurgery.

[33]  Christian Confavreux,et al.  Anti-aquaporin-4 antibodies in Devic’s neuromyelitis optica: therapeutic implications , 2010, Therapeutic advances in neurological disorders.

[34]  P. Agre,et al.  Aquaporin-4 square array assembly: Opposing actions of M1 and M23 isoforms , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[35]  I. Campbell,et al.  Developmental regulation of beta1 integrins during angiogenesis in the central nervous system. , 2002, Molecular and cellular neurosciences.

[36]  A. Tobeña,et al.  Early-life handling stimulation and environmental enrichment Are some of their effects mediated by similar neural mechanisms? , 2002, Pharmacology Biochemistry and Behavior.

[37]  A. Basbaum,et al.  Anatomical and functional analysis of aquaporin 1, a water channel in primary afferent neurons , 2007, Pain.

[38]  M. Sofroniew Molecular dissection of reactive astrogliosis and glial scar formation , 2009, Trends in Neurosciences.

[39]  Scott Barbay,et al.  Reorganization of motor cortex after controlled cortical impact in rats and implications for functional recovery. , 2010, Journal of neurotrauma.

[40]  P. Magistretti,et al.  Distribution of Aquaporin 9 in the adult rat brain: Preferential expression in catecholaminergic neurons and in glial cells , 2004, Neuroscience.

[41]  A. Obenaus,et al.  Posttraumatic Reduction of Edema with Aquaporin-4 RNA Interference Improves Acute and Chronic Functional Recovery , 2013, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[42]  G. Hu,et al.  Novel role of aquaporin‐4 in CD4+ CD25+ T regulatory cell development and severity of Parkinson’s disease , 2011, Aging cell.

[43]  W. Boron,et al.  Relative CO2/NH3 selectivities of AQP1, AQP4, AQP5, AmtB, and RhAG , 2009, Proceedings of the National Academy of Sciences.

[44]  H. Scharfman,et al.  Protective role of aquaporin‐4 water channels after contusion spinal cord injury , 2010, Annals of neurology.

[45]  P. Magistretti,et al.  Induction of brain aquaporin 9 (AQP9) in catecholaminergic neurons in diabetic rats , 2008, Brain Research.

[46]  F. Kirchhoff,et al.  Kir4.1 channels regulate swelling of astroglial processes in experimental spinal cord edema , 2007, Journal of neurochemistry.

[47]  G. Manley,et al.  Impaired pain sensation in mice lacking Aquaporin-1 water channels. , 2006, Biochemical and biophysical research communications.

[48]  E. Nagelhus,et al.  Aquaporin-4 in the central nervous system: Cellular and subcellular distribution and coexpression with KIR4.1 , 2004, Neuroscience.

[49]  P. Magistretti,et al.  Aquaporin 1 and aquaporin 4 expression in human brain after subarachnoid hemorrhage and in peritumoral tissue. , 2003, Acta neurochirurgica. Supplement.

[50]  M. Varrin-doyer,et al.  Proinflammatory role of aquaporin‐4 in autoimmune neuroinflammation , 2011, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[51]  G. Manley,et al.  Microfiberoptic fluorescence photobleaching reveals size‐dependent macromolecule diffusion in extracellular space deep in brain , 2008, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[52]  M. Papadopoulos,et al.  Aquaporin-4 in brain and spinal cord oedema , 2010, Neuroscience.

[53]  P. Shinnick‐Gallagher,et al.  Activities of neurons within the rat dorsolateral septal nucleus (DLSN) , 1995, Progress in Neurobiology.

[54]  G. Manley,et al.  Aquaporin-4 deletion in mice reduces brain edema after acute water intoxication and ischemic stroke , 2000, Nature Medicine.

[55]  Jing Zhao,et al.  Sulforaphane enhances aquaporin‐4 expression and decreases cerebral edema following traumatic brain injury , 2005, Journal of neuroscience research.

[56]  H. Konno,et al.  Disintegration of orthogonal arrays in perivascular astrocytic processes as an early event in acute global ischemia , 1984, Brain Research.

[57]  J. Badaut,et al.  Protective Role of Early Aquaporin 4 Induction against Postischemic Edema Formation , 2009, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[58]  J. Rafols,et al.  Hypoxia-inducible factor-1α signaling in aquaporin upregulation after traumatic brain injury , 2009, Neuroscience Letters.

[59]  T. Ben-Hur,et al.  Myasthenia gravis-associated neuromyelitis optica-like disease: an immunological link between the central nervous system and muscle? , 2011, Archives of neurology.

[60]  A. Verkman,et al.  Binding Affinity and Specificity of Neuromyelitis Optica Autoantibodies to Aquaporin-4 M1/M23 Isoforms and Orthogonal Arrays* , 2011, The Journal of Biological Chemistry.

[61]  A. Obenaus,et al.  Aquaporins in Cerebrovascular Disease: A Target for Treatment of Brain Edema , 2011, Cerebrovascular Diseases.

[62]  K. Yoo,et al.  Aquaporin 9 changes in pyramidal cells before and is expressed in astrocytes after delayed neuronal death in the ischemic hippocampal CA1 region of the gerbil , 2007, Journal of neuroscience research.

[63]  J. Badaut,et al.  Alteration of glucose metabolism in cultured astrocytes after AQP9-small interference RNA application , 2012, Brain Research.

[64]  J. Badaut,et al.  Presence of aquaporin-4 and muscarinic receptors in astrocytes and ependymal cells in rat brain: a clue to a common function? , 2000, Neuroscience Letters.

[65]  I. Campbell,et al.  Developmental Regulation of β1 Integrins during Angiogenesis in the Central Nervous System , 2002, Molecular and Cellular Neuroscience.

[66]  W. Poon,et al.  Heterogeneous responses of aquaporin-4 in oedema formation in a replicated severe traumatic brain injury model in rats , 2001, Neuroscience Letters.

[67]  M. Trojano,et al.  Aquaporin‐4 orthogonal arrays of particles are the target for neuromyelitis optica autoantibodies , 2009, Glia.

[68]  E. Nagelhus,et al.  Ontogeny of water transport in rat brain: postnatal expression of the aquaporin‐4 water channel , 1999, The European journal of neuroscience.

[69]  C. Colton,et al.  Vascular amyloid alters astrocytic water and potassium channels in mouse models and humans with Alzheimer's disease , 2009, Neuroscience.

[70]  Pierre J Magistretti,et al.  Aquaporins in Brain: Distribution, Physiology, and Pathophysiology , 2002, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[71]  J. Badaut,et al.  Delayed increase of astrocytic aquaporin 4 after juvenile traumatic brain injury: Possible role in edema resolution? , 2012, Neuroscience.

[72]  A. Obenaus,et al.  Brain Water Mobility Decreases after Astrocytic Aquaporin-4 Inhibition Using RNA Interference , 2011, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[73]  W. Liu,et al.  Cross talk between activation of microglia and astrocytes in pathological conditions in the central nervous system. , 2011, Life sciences.

[74]  A. Obenaus,et al.  Temporal and Regional Evolution of Aquaporin-4 Expression and Magnetic Resonance Imaging in a Rat Pup Model of Neonatal Stroke , 2007, Pediatric Research.

[75]  David Borsook,et al.  Neurological diseases and pain. , 2012, Brain : a journal of neurology.

[76]  Bao-song Liu,et al.  Swelling activated Cl- channels in microglia , 2011, Channels.

[77]  M. Schachner,et al.  Extracellular matrix molecules and synaptic plasticity , 2003, Nature Reviews Neuroscience.

[78]  J. Baraban,et al.  Molecular characterization of an aquaporin cDNA from brain: candidate osmoreceptor and regulator of water balance. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[79]  T. Zeuthen,et al.  Test of blockers of AQP1 water permeability by a high-resolution method: no effects of tetraethylammonium ions or acetazolamide , 2008, Pflügers Archiv - European Journal of Physiology.

[80]  T. Nakada,et al.  Identification of arylsulfonamides as Aquaporin 4 inhibitors. , 2007, Bioorganic & medicinal chemistry letters.

[81]  C. Brosnan,et al.  New possible roles for aquaporin‐4 in astrocytes: cell cytoskeleton and functional relationship with connexin43 , 2005, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[82]  D. Kleinfeld,et al.  Acute Vascular Disruption and Aquaporin 4 Loss After Stroke , 2009, Stroke.

[83]  J. Simard,et al.  Brain oedema in focal ischaemia: molecular pathophysiology and theoretical implications , 2007, The Lancet Neurology.

[84]  M. Mori,et al.  Association of anti-aquaporin-4 antibody-positive neuromyelitis optica with myasthenia gravis , 2009, Journal of the Neurological Sciences.

[85]  P. Chan,et al.  Myelin oligodendrocyte glycoprotein induces aquaporin-4 autoantibodies in mouse experimental autoimmune encephalomyelitis , 2013, Journal of Neuroimmunology.

[86]  A. Obenaus,et al.  Magnetic resonance imaging in cerebral ischemia: Focus on neonates , 2008, Neuropharmacology.

[87]  U. Tuor,et al.  Correspondence of AQP4 expression and hypoxic‐ischaemic brain oedema monitored by magnetic resonance imaging in the immature and juvenile rat , 2004, The European journal of neuroscience.

[88]  E. Nagelhus,et al.  Aquaporin-4 Water Channel Protein in the Rat Retina and Optic Nerve: Polarized Expression in Müller Cells and Fibrous Astrocytes , 1998, The Journal of Neuroscience.

[89]  M. Papadopoulos,et al.  Greatly improved neurological outcome after spinal cord compression injury in AQP4-deficient mice. , 2008, Brain : a journal of neurology.

[90]  A. Verkman,et al.  Microfiberoptic measurement of extracellular space volume in brain and tumor slices based on fluorescent dye partitioning. , 2010, Biophysical journal.

[91]  Y. Hiroaki,et al.  Acetazolamide reversibly inhibits water conduction by aquaporin-4. , 2009, Journal of structural biology.

[92]  Sergey Zelenin,et al.  Brain mitochondria contain aquaporin water channels: evidence for the expression of a short AQP9 isoform in the inner mitochondrial membrane , 2005, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[93]  Lien Tran,et al.  Bumetanide Inhibition of the Blood-Brain Barrier Na-K-Cl Cotransporter Reduces Edema Formation in the Rat Middle Cerebral Artery Occlusion Model of Stroke , 2004, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[94]  K. M. Baeten,et al.  Extracellular matrix and matrix receptors in blood–brain barrier formation and stroke , 2011, Developmental neurobiology.

[95]  J. Bogousslavsky,et al.  Time course of aquaporin expression after transient focal cerebral ischemia in mice , 2006, Journal of neuroscience research.

[96]  G. Manley,et al.  Expression of aquaporin water channels in mouse spinal cord , 2004, Neuroscience.

[97]  J. Badaut,et al.  Aquaporin 4: a player in cerebral edema and neuroinflammation , 2012, Journal of Neuroinflammation.

[98]  N. Meurice,et al.  Inhibition of Aquaporin-1 and Aquaporin-4 Water Permeability by a Derivative of the Loop Diuretic Bumetanide Acting at an Internal Pore-Occluding Binding Site , 2009, Molecular Pharmacology.

[99]  K. Holthoff,et al.  A Novel Role of Vasopressin in the Brain: Modulation of Activity-Dependent Water Flux in the Neocortex , 2001, The Journal of Neuroscience.

[100]  M. Sofroniew,et al.  Astrocytes: biology and pathology , 2009, Acta Neuropathologica.

[101]  C. Granziera,et al.  Astrocyte-Specific Expression of Aquaporin-9 in Mouse Brain is Increased after Transient Focal Cerebral Ischemia , 2001, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[102]  Shanquan Sun,et al.  Temporal changes in expression of aquaporin3, -4, -5 and -8 in rat brains after permanent focal cerebral ischemia , 2009, Brain Research.

[103]  Daniel C. Lu,et al.  Aquaporin-4 Reduces Post-Traumatic Seizure Susceptibility by Promoting Astrocytic Glial Scar Formation in Mice. , 2011, Journal of neurotrauma.

[104]  M. Salvetti,et al.  Neuromyelitis optica spectrum disorders in patients with myasthenia gravis: ten new aquaporin-4 antibody positive cases and a review of the literature , 2012, Multiple sclerosis.

[105]  M. Papadopoulos,et al.  Intra-cerebral injection of neuromyelitis optica immunoglobulin G and human complement produces neuromyelitis optica lesions in mice. , 2010, Brain : a journal of neurology.

[106]  D. Nampiaparampil Prevalence of chronic pain after traumatic brain injury: a systematic review. , 2008, JAMA.

[107]  C. Nicholson,et al.  Aquaporin-4-Deficient Mice Have Increased Extracellular Space without Tortuosity Change , 2008, The Journal of Neuroscience.

[108]  M. Romero,et al.  Molecular outcomes of neuromyelitis optica (NMO)-IgG binding to aquaporin-4 in astrocytes , 2011, Proceedings of the National Academy of Sciences.

[109]  O. Ottersen,et al.  Na+–K+–2Cl− Cotransport Inhibitor Attenuates Cerebral Edema Following Experimental Stroke via the Perivascular Pool of Aquaporin-4 , 2010, Neurocritical care.

[110]  N. Hattori,et al.  Anti-aquaporin-4 Antibody-positive Definite Neuromyelitis Optica in a Patient With Thymectomy for Myasthenia Gravis , 2012, The neurologist.

[111]  G. Manley,et al.  Aquaporin‐4 facilitates reabsorption of excess fluid in vasogenic brain edema , 2004, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[112]  Bruno Brochet,et al.  Aquaporin 4 correlates with apparent diffusion coefficient and hydrocephalus severity in the rat brain: A combined MRI–histological study , 2009, NeuroImage.

[113]  J. Badaut,et al.  Endothelial Cells and Astrocytes: A Concerto en Duo in Ischemic Pathophysiology , 2012, International journal of cell biology.

[114]  Tamir Gonen,et al.  Aquaporin-0 membrane junctions reveal the structure of a closed water pore , 2004, Nature.

[115]  Tamir Gonen,et al.  The structure of aquaporins , 2006, Quarterly Reviews of Biophysics.

[116]  C. Hulsebosch,et al.  Aquaporin 1 – a novel player in spinal cord injury , 2008, Journal of neurochemistry.

[117]  P. Agre,et al.  Specialized Membrane Domains for Water Transport in Glial Cells: High-Resolution Immunogold Cytochemistry of Aquaporin-4 in Rat Brain , 1997, The Journal of Neuroscience.

[118]  B. Cauli,et al.  Revisiting the Role of Neurons in Neurovascular Coupling , 2010, Front. Neuroenerg..

[119]  S. Kirov,et al.  Real‐time passive volume responses of astrocytes to acute osmotic and ischemic stress in cortical slices and in vivo revealed by two‐photon microscopy , 2009, Glia.

[120]  A. Verkman,et al.  Lack of aquaporin-4 water transport inhibition by antiepileptics and arylsulfonamides. , 2008, Bioorganic & medicinal chemistry.

[121]  Peter M Haggie,et al.  In Vivo Measurement of Brain Extracellular Space Diffusion by Cortical Surface Photobleaching , 2004, The Journal of Neuroscience.

[122]  H. Nawashiro,et al.  Effect of decompressive craniectomy on aquaporin-4 expression after lateral fluid percussion injury in rats. , 2011, Journal of neurotrauma.

[123]  T. Nakada,et al.  Inhibition of aquaporin 4 by antiepileptic drugs. , 2009, Bioorganic & medicinal chemistry.

[124]  J. Frank,et al.  The contribution of gliosis to diffusion tensor anisotropy and tractography following traumatic brain injury: validation in the rat using Fourier analysis of stained tissue sections. , 2011, Brain : a journal of neurology.

[125]  S. Davies,et al.  Molecular mechanisms of cerebrospinal fluid production , 2004, Neuroscience.

[126]  H. Wolburg,et al.  Astrocytic autoantibody of neuromyelitis optica (NMO-IgG) binds to aquaporin-4 extracellular loops, monomers, tetramers and high order arrays. , 2013, Journal of autoimmunity.

[127]  Ichiro Nakashima,et al.  A serum autoantibody marker of neuromyelitis optica: distinction from multiple sclerosis , 2004, The Lancet.

[128]  D. Stein,et al.  Progesterone administration modulates AQP4 expression and edema after traumatic brain injury in male rats , 2006, Experimental Neurology.

[129]  Kazushi Kimura,et al.  Implications of the aquaporin-4 structure on array formation and cell adhesion. , 2006, Journal of molecular biology.

[130]  J. Pachter,et al.  Where is the blood–brain barrier … really? , 2005, Journal of neuroscience research.