| http://purl.uniprot.org/citations/15379997 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/15379997 | http://www.w3.org/2000/01/rdf-schema#comment | "Early deterioration and death after brain injury is often the result of oedema in the injured and peri-lesional tissue. So far, no pharmacotherapy is available that exhibits significant brain oedema-reducing efficacy in patients. We selected two low molecular weight compounds from different chemical classes, a triazole (1-[(2-chlorophenyl)diphenylmethyl]-1,2,3-triazole) and a cyclohexadiene (methyl 4-[4-chloro-3-(trifluoromethyl)phenyl]-6-methyl-3-oxo-1,4,7-tetrahydroisobenzofuran-5-carboxylate) to characterize their pharmacological properties on KCNN4 channels (intermediate/small conductance calcium-activated potassium channel, subfamily N, member 4) in vitro as well as in vivo. In vitro we replaced potassium by rubidium (Rb+) and determined Rb+ fluxes evoked by 10 micro m of the calcium ionophore A23187 on C6BU1 rat glioma cells. Compared with known KCNN4 blockers, such as clotrimazole (IC50=360 +/-12 nm) and charybdotoxin (IC50=3.3 +/-1.9 nm), the triazole and cyclohexadiene were considerably more potent than clotrimazole and displayed similar potencies (IC50=12.1 +/- 8.8 and 13.3 +/-4.7 nm, respectively). In the rat acute subdural haematoma model, both the triazole and cyclohexadiene displayed reduction of brain water content (-26% at 0.3 mg/kg and -24% at 0.01 mg/kg) and reduction of the intracranial pressure (-46% at 0.1 mg/kg and -60% at 0.003 mg/kg) after 24 h when administered as a 4-h infusion immediately after brain injury. When infarct volumes were determined after 7 days, the triazole as well as the cyclohexadiene displayed strong neuroprotective efficacy (-52% infarct volume reduction at 1.2 mg/kg and -43% at 0.04 mg/kg, respectively). It is concluded that blockade of KCNN4 channels is a new pharmacological approach to attenuate acute brain damage caused by traumatic brain injury."xsd:string |
| http://purl.uniprot.org/citations/15379997 | http://purl.org/dc/terms/identifier | "doi:10.1111/j.1460-9568.2004.03615.x"xsd:string |
| http://purl.uniprot.org/citations/15379997 | http://purl.uniprot.org/core/author | "Hahn M.G."xsd:string |
| http://purl.uniprot.org/citations/15379997 | http://purl.uniprot.org/core/author | "Schuhmacher J."xsd:string |
| http://purl.uniprot.org/citations/15379997 | http://purl.uniprot.org/core/author | "Horvath E."xsd:string |
| http://purl.uniprot.org/citations/15379997 | http://purl.uniprot.org/core/author | "Wirtz S."xsd:string |
| http://purl.uniprot.org/citations/15379997 | http://purl.uniprot.org/core/author | "Hofmann H.A."xsd:string |
| http://purl.uniprot.org/citations/15379997 | http://purl.uniprot.org/core/author | "Mauler F."xsd:string |
| http://purl.uniprot.org/citations/15379997 | http://purl.uniprot.org/core/author | "Hinz V."xsd:string |
| http://purl.uniprot.org/citations/15379997 | http://purl.uniprot.org/core/author | "Urbahns K."xsd:string |
| http://purl.uniprot.org/citations/15379997 | http://purl.uniprot.org/core/date | "2004"xsd:gYear |
| http://purl.uniprot.org/citations/15379997 | http://purl.uniprot.org/core/name | "Eur J Neurosci"xsd:string |
| http://purl.uniprot.org/citations/15379997 | http://purl.uniprot.org/core/pages | "1761-1768"xsd:string |
| http://purl.uniprot.org/citations/15379997 | http://purl.uniprot.org/core/title | "Selective intermediate-/small-conductance calcium-activated potassium channel (KCNN4) blockers are potent and effective therapeutics in experimental brain oedema and traumatic brain injury caused by acute subdural haematoma."xsd:string |
| http://purl.uniprot.org/citations/15379997 | http://purl.uniprot.org/core/volume | "20"xsd:string |
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