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Neurocrit Care
2010 Aug 01;131:123-31. doi: 10.1007/s12028-010-9376-8.
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Na(+)-K (+)-2Cl (-) cotransport inhibitor attenuates cerebral edema following experimental stroke via the perivascular pool of aquaporin-4.
Migliati ER
,
Amiry-Moghaddam M
,
Froehner SC
,
Adams ME
,
Ottersen OP
,
Bhardwaj A
.
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The Na(+)-K(+)-2Cl(-) cotransporter localized in the brainvascular endothelium has been shown to be important in the evolution of cerebral edema following experimental stroke. Previous in vivo studies have demonstrated that bumetanide, a selective Na(+)-K(+)-2Cl(-) cotransport inhibitor, attenuates ischemia-evoked cerebral edema. Recently, bumetanide has been shown to also inhibit water permeability via aquaporin-4 (AQP4) expressed in Xenopus laevis oocytes. We tested the hypothesis that the perivascular pool of AQP4 plays a significant role in the anti-edema effect of bumetanide by utilizing wild-type (WT) mice as well as mice with targeted disruption of alpha-syntrophin (alpha-Syn(-/-)) that lack the perivascular pool of AQP4. Isoflurane-anesthetized adult male WT C57Bl6 and alpha-Syn(-/-) mice were subjected to 90 min middle cerebral artery occlusion (MCAO) followed by 24 or 48 h of reperfusion. Adequacy of MCAO and reperfusion was monitored with laser-Doppler flowmetry over the ipsilateral parietal cortex. Infarct volume (tetrazolium staining), cerebral edema (wet-to-dry ratios), and AQP4 protein expression (immunoblotting) were determined in different treatment groups in separate sets of experiments. Bumetanide significantly attenuated infarct volume and decreased ipsilateral hemispheric water content in WT mice compared to vehicle treatment. In alpha-Syn(-/-) mice, bumetanide treatment had no effect on infarct volume or ischemia-evoked cerebral edema. Bumetanide-treated WT mice had a significant attenuation of AQP4 protein expression at 48 h post-MCAO compared to vehicle-treated WT mice. These data suggest that bumetanide exerts its neuroprotective and anti-edema effects partly via blockade of the perivascular pool of AQP4 and may have therapeutic potential for ischemic stroke in the clinical setting.
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Adams,
Absence of alpha-syntrophin leads to structurally aberrant neuromuscular synapses deficient in utrophin.
2000, Pubmed
Adams,
Absence of alpha-syntrophin leads to structurally aberrant neuromuscular synapses deficient in utrophin.
2000,
Pubmed
Amiry-Moghaddam,
Alpha-syntrophin deletion removes the perivascular but not endothelial pool of aquaporin-4 at the blood-brain barrier and delays the development of brain edema in an experimental model of acute hyponatremia.
2004,
Pubmed
Amiry-Moghaddam,
An alpha-syntrophin-dependent pool of AQP4 in astroglial end-feet confers bidirectional water flow between blood and brain.
2003,
Pubmed
Ayata,
Ischaemic brain oedema.
2002,
Pubmed
Badaut,
Aquaporins in brain: distribution, physiology, and pathophysiology.
2002,
Pubmed
Berrouschot,
Mortality of space-occupying ('malignant') middle cerebral artery infarction under conservative intensive care.
1998,
Pubmed
Bhardwaj,
Osmotherapy in neurocritical care.
2007,
Pubmed
Chen,
Effect of duration of osmotherapy on blood-brain barrier disruption and regional cerebral edema after experimental stroke.
2006,
Pubmed
Foroutan,
Moderate-to-severe ischemic conditions increase activity and phosphorylation of the cerebral microvascular endothelial cell Na+-K+-Cl- cotransporter.
2005,
Pubmed
Frigeri,
Localization of MIWC and GLIP water channel homologs in neuromuscular, epithelial and glandular tissues.
1995,
Pubmed
Frydenlund,
Temporary loss of perivascular aquaporin-4 in neocortex after transient middle cerebral artery occlusion in mice.
2006,
Pubmed
Haas,
The Na-K-Cl cotransporters.
1994,
Pubmed
Haas,
Bumetanide inhibits (Na + K + 2Cl) co-transport at a chloride site.
1983,
Pubmed
Hamann,
Water permeability of Na+-K+-2Cl- cotransporters in mammalian epithelial cells.
2005,
Pubmed
Hara,
Reduced brain edema and infarction volume in mice lacking the neuronal isoform of nitric oxide synthase after transient MCA occlusion.
1996,
Pubmed
Kako,
Examination of DNA-binding activity of neuronal transcription factors by electrophoretical mobility shift assay.
1998,
Pubmed
Kimelberg,
Current concepts of brain edema. Review of laboratory investigations.
1995,
Pubmed
King,
Pathophysiology of the aquaporin water channels.
1996,
Pubmed
Klatzo,
Presidental address. Neuropathological aspects of brain edema.
1967,
Pubmed
Kumar,
Effects of chloride flux modulators in an in vitro model of brain edema formation.
2006,
Pubmed
Lin,
Effect of brain edema on infarct volume in a focal cerebral ischemia model in rats.
1993,
Pubmed
Liu,
Lack of sex-linked differences in cerebral edema and aquaporin-4 expression after experimental stroke.
2008,
Pubmed
MacAulay,
Water transport in the brain: role of cotransporters.
2004,
Pubmed
,
Xenbase
Manley,
Aquaporin-4 deletion in mice reduces brain edema after acute water intoxication and ischemic stroke.
2000,
Pubmed
McClain,
Toxicologic evaluation of bumetanide, potent diuretic agent.
1981,
Pubmed
Menzies,
Contributions of ions and albumin to the formation and resolution of ischemic brain edema.
1993,
Pubmed
Migliati,
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,
Pubmed
,
Xenbase
Neely,
Syntrophin-dependent expression and localization of Aquaporin-4 water channel protein.
2001,
Pubmed
Nielsen,
Specialized membrane domains for water transport in glial cells: high-resolution immunogold cytochemistry of aquaporin-4 in rat brain.
1997,
Pubmed
O'Donnell,
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,
Pubmed
O'Donnell,
Arginine vasopressin stimulation of cerebral microvascular endothelial cell Na-K-Cl cotransporter activity is V1 receptor and [Ca] dependent.
2005,
Pubmed
O'Donnell,
Estradiol reduces activity of the blood-brain barrier Na-K-Cl cotransporter and decreases edema formation in permanent middle cerebral artery occlusion.
2006,
Pubmed
Ouyang,
Tetanic stimulation leads to increased accumulation of Ca(2+)/calmodulin-dependent protein kinase II via dendritic protein synthesis in hippocampal neurons.
1999,
Pubmed
Papadopoulos,
Aquaporin-4 facilitates reabsorption of excess fluid in vasogenic brain edema.
2004,
Pubmed
Plotkin,
Expression of the Na(+)-K(+)-2Cl- cotransporter BSC2 in the nervous system.
1997,
Pubmed
Sawada,
Estrogen receptor antagonist ICI182,780 exacerbates ischemic injury in female mouse.
2000,
Pubmed
Schielke,
Blood to brain sodium transport and interstitial fluid potassium concentration during early focal ischemia in the rat.
1991,
Pubmed
Suvitayavat,
Characterization of the endogenous Na(+)-K(+)-2Cl- cotransporter in Xenopus oocytes.
1994,
Pubmed
,
Xenbase
Toung,
Osmotherapy with hypertonic saline attenuates water content in brain and extracerebral organs.
2007,
Pubmed
Vajda,
Delayed onset of brain edema and mislocalization of aquaporin-4 in dystrophin-null transgenic mice.
2002,
Pubmed
Yan,
Inhibition of Na(+)-K(+)-Cl(-) cotransporter during focal cerebral ischemia decreases edema and neuronal damage.
2003,
Pubmed
Yan,
Na+-K+-Cl- cotransporter in rat focal cerebral ischemia.
2001,
Pubmed
Yang,
Human copper-zinc superoxide dismutase transgenic mice are highly resistant to reperfusion injury after focal cerebral ischemia.
1994,
Pubmed
Yuen,
Cerebral blood flow and cerebral edema in rats with diabetic ketoacidosis.
2008,
Pubmed
Zeynalov,
The perivascular pool of aquaporin-4 mediates the effect of osmotherapy in postischemic cerebral edema.
2008,
Pubmed
