Oxidative stress and antioxidant strategies in experimental cerebral ischemia

Mracskó, Éva Zsuzsanna
Oxidative stress and antioxidant strategies in experimental cerebral ischemia.
[Thesis] (Unpublished)

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Abstract in foreign language

Oxidative stress plays an important role in the pathomechanism of ischemic neuronal death. In our experiments we investigated the changes of pro- and antioxidant enzyme levels in different models of cerebral ischemia, and examined the potential protective effects of certain antioxidant treatment strategies in these models. We characterized the changes of cyclooxygenase-2 (COX-2), the 3 nitric oxide synthase (NOS) isoforms and manganase superoxide dysmutase levels in the hippocampus and in the cortex in different phases (between 1 day and 12 months) of mild forebrain ischemia induced by the permanent occlusion of the common carotid arteries in rats (2VO=2 vessel occlusion) and 3 days following 10 min severe forebrain ischemia (TGI = transient global ischemia) induced by 2VO combined with hypovolemic hypotension in rats. We investigated the effects of the vitamin E component α-tocopherol in the 2VO model, and hydrogen therapy in TGI. To examine the participation of leukocyte infiltration in oxidative stress, we induced focal ischemia by medial cerebral artery occlusion in mice and investigated the effect of CD8+ T cell depletion on neuronal damage and the expression of inducible NOS (iNOS). In the acute phase of both forebrain ischemia models, we described COX-2 upregulation indicating the presence of excitotoxicity and decreased neuronal NOS expression referring to neuronal loss in the hippocampus, which is the most vulnerable part of the brain to oxidative damage. These responses were more moderate and developed with a delayed dynamics following 2VO suggesting a more severe neuronal damage in TGI. In the late phase (12 months) of the 2VO model, endothelial NOS is upregulated and can contribute to the compensation of cerebral perfusion. iNOS was induced only in focal ischemia, CD8+ T cell depletion attenuated its upregulation resulting in smaller infarct size and improved sensorimotor functions. These results suggest a deleterious effect of iNOS in focal ischemia, where its overexpression predominates in infiltrating leukocytes, such as CD8+ T cells. α-Tocopherol treatment prevented neuronal loss and attenuated learning deficit in the 2VO model of chronic hypoperfusion seen is Alzheimer disease (AD) and normal aging. Hydrogen containing room air inhalation prevented the changes of the investigated enzyme levels induced by TGI, that occurs in patients during acute severe hypotension of cardiac origin. Therefore, α-tocopherol may prevent the development of AD and normal aging-coupled memory dysfunctions, while hydrogen therapy should be considered in the acute management of cardiovascular emergencies and / or cardiac surgery.

Item Type: Thesis (PhD)
Creators: Mracskó, Éva Zsuzsanna
Hungarian title label: Oxidatív stressz és antioxidáns kezelési stratégiák kísérletes agyi iszkémiában
Divisions: Doctoral School of Theoretical Medicine
Discipline label: Medicine > Theoretical Medicine
Defence date label: 2011. November 28.
Item ID: 1275
MTMT id: 1934263
doi: https://doi.org/10.14232/phd.1275
Date Deposited: 2011. Nov . 21. 10:33
Last Modified: 2019. Sep . 26. 09:22
URI: https://doktori.bibl.u-szeged.hu/id/eprint/1275
Defence/Citable status: Defended.

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