Oxidative stress in acute ischemic stroke

doi:10.1016/j.jocn.2006.11.008

Journal of Clinical Neuroscience

Volume 14, Issue 11, November 2007, Pages 1062-1066

https://doi.org/10.1016/j.jocn.2006.11.008 Get rights and content

Abstract

Oxidative stress plays an important role in acute ischemic stroke pathogenesis. Free radical formation and subsequent oxidative damage may be a factor in stroke severity. Serum levels of nitric oxide (NO), malondialdehyde (MDA) and glutathione (GSH) were measured within the first 48 h of stroke in 70 patients. The levels were also correlated with the clinical outcomes using Canadian Neurological Scale (CNS) scores. The results were compared with a control group consisting of 70 volunteers with similar stroke risk factors. Serum NO, MDA and GSH levels were significantly elevated in acute stroke patients. CNS score was negatively correlated with both MDA and NO levels. However, no statistically significant correlation between GSH levels and CNS scores was detected. Our results suggest deleterious effects of oxidative stress on clinical outcome in acute ischemic stroke. The elevation of GSH levels may be an adaptive mechanism during this period.

Introduction

In acute cerebral infarct, fractional uptake of oxygen in brain tissue is not sufficient to maintain cellular oxidative metabolism. This causes metabolic changes and possibly cellular death. The brain is especially prone to free radical damage for several reasons. It is very rich in polyunsaturated fatty acids, which are particularly vulnerable to free radical induced peroxidation, but also has a low content of antioxidant enzymes, such as catalase and glutathione peroxidase.¹ It is proposed that ischemia causes release of nitric oxide (NO) from the vascular endothelium in an attempt to limit the degree of damage by increasing local blood flow.² As ischemia develops and infarct evolves, NO may have a more deleterious effect.³ Restoration of blood flow could have negative consequences such as generation of free oxygen radicals. Superoxide $(O_{2}^{-})$ and hydroxyl (–OH) react with unsaturated lipids of biomembranes, resulting in the generation of lipid peroxide radicals, lipid hydroperoxides, and fragmentation products such as malondialdehyde (MDA).⁴

Glutathione (GSH) is a sulfhydryl (SH) containing tripeptide (Glu-Cys-Gly). It has several major physiological functions: it maintains SH groups of proteins in a reduced state, participates in amino acid transport, detoxifies foreign compounds, enzymatically degenerates endogenous peroxides, forms bioactive molecules, and acts as a coenzyme in several enzymatic reactions.⁵ It possibly acts as a major defense against the toxicity of reactive oxygen species (ROS) and reactive nitrogen species (RNS) in the brain.⁶ GSH reacts readily and favorably with RNS, thus affording cellular protection against oxidative damage.[7], [8]

Thus, MDA and NO can be used as biochemical markers for tissue damage and reperfusion, while GSH levels can be used to evaluate the defence mechanism against oxidative stress in acute cerebral ischemia. This study was designed to examine the serum levels of NO, MDA, and GSH in acute ischemic stroke and the correlations between them and with stroke severity. Free radical formation and subsequent oxidative damage may affect stroke severity.

Section snippets

Materials and methods

We included in our study 70 acute cerebral ischemic infarct patients who were admitted to the neurology department of Adnan Menderes University Medical Faculty between January 2004 and March 2005, along with 70 volunteers as a control group. The control group included volunteers with similar cerebrovascular risk factors. Neither patients nor controls had a previous history of a cerebrovascular event, cerebral hemorrhage, hemorrhagic infarct or transient ischemic attack. Those with a history of

Statistical analyses

The Statistical Package for the Social Sciences (SPSS) 13.0 (SPSS Inc., Chicago, IL, USA) was used for statistical analysis and statistical significance was defined as p < 0.05. Results were given as mean ± standard deviation. Comparisons of numeric values of all variables were performed using the Mann–Whitney U-test or Student’s t-test. Chi-square tests were used for analyzing categorical variables. We tested whether or not the variables which were detected in numeric scales in both groups had

Results

This study included 70 acute ischemic stroke patients, of whom 33 were female (47.1%), and 37 were male (52.9%). Their ages were between 42 and 90 years (mean, 64.3 ± 9.2). The control group consisted of 70 volunteers with ages between 45 and 82 years (mean, 62.1 ± 7.9). There were 33 females (47.1%) and 37 males (52.9%) in this group. Blood samples were taken within the first 48 h. There was no significant difference between the patient and control groups with regard to age or gender (p > 0.05).

Discussion

Oxidative stress is one of the mechanisms involved in neuronal damage induced by ischemia.[13], [14] Acute ischemia leads to increased production of free radicals and ROS in tissue and plasma.[1], [13] The increased production of free radicals in acute cerebral ischemia, with or without reperfusion, can arise from several mechanisms. These are stimulation of N-methyl-D-aspartate (NMDA) receptors,¹⁵ mitochondrial dysfunction,[16], [17] activation of neuronal nitric oxide synthase (NOS),¹⁸

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Clinical StudyOxidative stress in acute ischemic stroke

Abstract

Introduction

Section snippets

Materials and methods

Statistical analyses

Results

Discussion

Free Radic Biol Med

Mol Aspects Med

Neurochem Int

Prog Neurobiol

Anal Biochem

Anal Biochem

Free Rad Biol Med

Neurochem Int

Brain Res Brain Res Rev

Increased serum malondialdehyde and decreased nitric oxide within 24 h of thrombotic stroke onset

Am J Ther

Biological chemistry of thiols in the vasculature and in vascular related diseases

Nutr Rev

Impairment of brain mitochondrial function of reactive nitrogen species: the role of glutathione in dictating susceptibility

Eurochem Int

Interactions of mitochondrial thiols with nitric oxide

Antioxid Redox Signal

Ontario regional stroke centres: survey of neurological nursing assessment practices with acute stroke patients

Axone

Semiautomated measurement of nitrate in biological fluids

Clin Chem

Pathophysioloy of ischaemia-reperfusion injury

J Pathol

Role of oxidants in ischemic brain damage

Stroke

NMDA dependent superoxide production and neurotoxicity

Nature

Mitochondrial generation of reactive oxygen species after brain ischemia in the rat

Stroke

Excitatory amino acids as a final common pathway for neurological disorders

N Engl J Med

Clinical Study
Oxidative stress in acute ischemic stroke