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Int J Mol Sci ; 21(23)2020 Nov 24.
Artículo en Inglés | MEDLINE | ID: mdl-33255506

RESUMEN

Effective pharmacological neuroprotection is one of the most desired aims in modern medicine. We postulated that a combination of two clinically used drugs-nimodipine (L-Type voltage-gated calcium channel blocker) and amiloride (acid-sensing ion channel inhibitor)-might act synergistically in an experimental model of ischaemia, targeting the intracellular rise in calcium as a pathway in neuronal cell death. We used organotypic hippocampal slices of mice pups and a well-established regimen of oxygen-glucose deprivation (OGD) to assess a possible neuroprotective effect. Neither nimodipine (at 10 or 20 µM) alone or in combination with amiloride (at 100 µM) showed any amelioration. Dissolved at 2.0 Vol.% dimethyl-sulfoxide (DMSO), the combination of both components even increased cell damage (p = 0.0001), an effect not observed with amiloride alone. We conclude that neither amiloride nor nimodipine do offer neuroprotection in an in vitro ischaemia model. On a technical note, the use of DMSO should be carefully evaluated in neuroprotective experiments, since it possibly alters cell damage.


Asunto(s)
Canales Iónicos Sensibles al Ácido/genética , Amilorida/farmacología , Isquemia Encefálica/tratamiento farmacológico , Canales de Calcio Tipo L/genética , Nimodipina/farmacología , Canales Iónicos Sensibles al Ácido/metabolismo , Canales Iónicos Sensibles al Ácido/farmacología , Amilorida/efectos adversos , Animales , Isquemia Encefálica/metabolismo , Isquemia Encefálica/patología , Canales de Calcio Tipo L/efectos de los fármacos , Canales de Calcio Tipo L/metabolismo , Células Cultivadas , Glucosa/metabolismo , Hipocampo/efectos de los fármacos , Hipocampo/metabolismo , Humanos , Ratones , Neuronas/efectos de los fármacos , Neuronas/metabolismo , Fármacos Neuroprotectores/efectos adversos , Fármacos Neuroprotectores/farmacología , Nimodipina/efectos adversos , Oxígeno/metabolismo
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