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

Mitochondrion. 2013 Sep;13(5):539-47. doi: 10.1016/j.mito.2012.07.110. Epub 2012 Jul 21.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Respiration*
  • Cyclosporins / metabolism*
  • Dizocilpine Maleate / metabolism*
  • Glucose / metabolism*
  • Hippocampus / drug effects
  • Hippocampus / physiology*
  • In Vitro Techniques
  • Male
  • Mitochondria / drug effects
  • Mitochondria / metabolism
  • Neuroprotective Agents / metabolism*
  • Oxygen / metabolism*
  • Rats
  • Rats, Wistar


  • Cyclosporins
  • Neuroprotective Agents
  • Dizocilpine Maleate
  • Glucose
  • Oxygen