Failed Neuroprotection of Combined Inhibition of L-Type and ASIC1a Calcium Channels with Nimodipine and Amiloride |
| |
| Authors: | Jonas Ort Benedikt Kremer Linda Grüßer Romy Blaumeiser-Debarry Hans Clusmann Mark Coburn Anke Hllig Ute Lindauer |
| |
| Affiliation: | 1.Department of Neurosurgery, Medical Faculty, RWTH Aachen University, 52074 Aachen, Germany; (B.K.); (H.C.); (A.H.); (U.L.);2.Department of Anaesthesiology, Medical Faculty, RWTH Aachen University, 52074 Aachen, Germany; (L.G.); (R.B.-D.);3.Department of Anaesthesiology and Intensive Care Medicine, University Hospital Bonn, 53127 Bonn, Germany; |
| |
| Abstract: | 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. |
| |
| Keywords: | neuroprotection neural injury nimodipine subarachnoid haemorrhage acid-sensing ion channels amiloride oxygen-glucose deprivation |
|
|
