We have introduced a sensitive method for studying oxygen/glucose deprivation (OGD)-induced mitochondrial alterations in homogenates of organotypic hippocampal slice cultures (slices) by high-resolution respirometry. Using this approach, we tested the neuroprotective potential of the novel non-immunosuppressive cyclosporin (CsA) derivative Cs9 in comparison with CsA, the immunosuppressive CsA analog [D-Ser](8)CsA, and MK 801, a N-methyl-d-aspartate (NMDA) receptor antagonist. OGD/reperfusion reduced the glutamate/malate dependent (and protein-related) state 3 respiration to 30% of its value under control conditions. All of the above drugs reversed this effect, with an increase to >88% of the value for control slices not exposed to OGD. We conclude that Cs9, [D-Ser](8)CsA, and MK 801, despite their different modes of action, protect mitochondria from OGD-induced damage.
Keywords: (MMF); 5,5′-dithiobis-(2-nitrobenzoic acid); BCA; Bicinchoninic acid; CPEO; CS; Cs9; DTNB; Mitochondria; N-methyl-d-aspartate; NMDA; OGD; Organotypic hippocampal slice cultures; Oxygen/glucose deprivation; PI; PT; RCI; SD; chronic progressive external ophthalmoplegia; citrate synthase; mitochondrial main function; organotypic hippocampal slices; oxygen/glucose deprivation; permeability transition; propidium iodide; respiratory control indices; slices; standard deviation.
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