title: Oxygen glucose deprivation causes mitochondrial dysfunction in cultivated rat hippocampal slices: protective effects of CsA, its immunosuppressive congener [D-Ser](8)CsA, the novel non-immunosuppressive cyclosporin derivative Cs9, and the NMDA receptor antagonist MK 801.
abstract: 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.
authors: Institute of Neurosciences, Lithuanian University of Health Sciences, Eiveniu Str. 4, 50009 Kaunas, Lithuania. sonatai@centras.lt
authors: Sonata
authors: S
authors: Trumbeckaite
authors: Zemfira
authors: Z
authors: Gizatullina
authors: Odeta
authors: O
authors: Arandarcikaite
authors: Peter
authors: P
authors: Röhnert
authors: Stefan
authors: S
authors: Vielhaber
authors: Miroslav
authors: M
authors: Malesevic
authors: Gunter
authors: G
authors: Fischer
authors: Enn
authors: E
authors: Seppet
authors: Frank
authors: F
authors: Striggow
authors: Frank Norbert
authors: FN
authors: Gellerich
mesh_terms: D000818:Animals; D019069:Cell Respiration; D003524:Cyclosporins / Q000378:metabolism*; D016291:Dizocilpine Maleate / Q000378:metabolism*; D005947:Glucose / Q000378:metabolism*; D006624:Hippocampus / Q000187:drug effects / Q000502:physiology*; D066298:In Vitro Techniques; D008297:Male; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D018696:Neuroprotective Agents / Q000378:metabolism*; D010100:Oxygen / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D003524:Cyclosporins; D018696:Neuroprotective Agents; D016291:Dizocilpine Maleate; D005947:Glucose; D010100:Oxygen