Abstract ........................................................ 4
Tiivistelmä (in Finnish) ........................................ 5
Аннотация (in Russian) .......................................... 6
Table of contents ............................................... 8
List of abbreviations .......................................... 10
List of original publications .................................. 12
1 Introduction ................................................ 14
2 Review of the literature .................................... 16
2.1 Hypoxia: experimental models ........................... 16
2.2 Free radicals and oxidative stress ..................... 17
2.3 The role of oxidative stress in the induction of
nerve cell damage ...................................... 19
2.4 The role of intracellular antioxidants in molecular
mechanisms of neuroprotection .......................... 25
2.4.1 Thioredoxins .................................... 27
2.4.2 Superoxide dismutases ........................... 36
2.5 Hypobaric hypoxia ...................................... 43
2.6 Preconditioning ........................................ 45
3 Aims of the study ........................................... 53
4 Materials and methods ....................................... 54
4.1 Animals ................................................ 54
4.2 Hypoxia procedures ..................................... 54
4.3 Determination of Cu, Zn-SOD enzyme activity ............ 55
4.4 Immunocytochemical analysis of protein expression ...... 57
4.5 Statistical analysis of the data ....................... 63
5 Results ..................................................... 64
5.1 Cu, Zn-SOD enzyme activity ............................. 64
5.2 Effects of non- and preconditioned severe hypobaric
hypoxia on the expression of antioxidants .............. 65
5.2.1 Effect of non-preconditioned severe hypoxia
compared with the control ....................... 70
5.2.2 Effect of preconditioned severe hypobaric
hypoxia compared with the control ............... 72
5.2.3 Effect of preconditioning with 3 sessions of
mild hypobaric hypoxia after subsequent severe
hypoxia compared with non-preconditioning ....... 75
5.3 Effect of 3 sessions and 1 session of mild hypobaric
hypoxia (preconditioning itself without severe
hypoxia) on the expression of antioxidants ............. 77
5.3.1 Effect of 3 sessions of mild hypoxia ............ 82
5.3.2 Effect of 1 session of mild hypoxia ............. 84
5.3.3 Effect of 3 sessions of mild hypoxia compared
with the effect of 1 session of mild hypoxia .... 87
6 Discussion .................................................. 90
6.1 The effect of non-preconditioned severe hypoxia on
the expression of antioxidant proteins ................. 90
6.2 The effect of preconditioning on the expression of
antioxidant proteins after severe hypoxia .............. 94
6.3 The effect of 3 sessions of mild hypoxia on the
expression of antioxidant proteins ..................... 98
6.4 The effect of 1 session of mild hypoxia on the
expression of antioxidant proteins .................... 101
6.5 The effect of non- and preconditioned severe hypoxia
on the enzymatic activity of Cu, Zn-SOD ............... 102
6.6 Protein and mRNA expression of antioxidants after
non- and preconditioned severe hypoxia ................ 104
6.7 Methodological limitations of the research and
future directions ..................................... 106
6.8 Summary ............................................... 107
7 Conclusions ................................................ 109
Acknowledgements .............................................. 1ll
References .................................................... 118
Original publications ......................................... 159
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