The early hours after an acute stroke are crucial; it is the most useful time for effective management. With the rising burden of stroke and marked heterogeneity in stroke manifestation and outcome, it is necessary to find accurate, reliable, and simple predictors of functional recovery .
Accumulating evidences suggest that oxidative stress and inflammation play a crucial role in the pathophysiology of acute ischemic stroke . The accurate measurement of oxidative stress in stroke would be of extreme value for a better understanding of its pathophysiology and for identifying patients' subgroups that might benefit from receiving targeted therapeutic intervention . Blood biomarkers of oxidative stress can be used as early indicators of stroke. Currently, an accurate and valid biomarker is still under investigations .
Several studies reported a close relation between increased expression of thioredoxin and cell damage due to oxidative stress. Thioredoxin system is up regulated in postmortem examination of Alzheimer disease in human and after experimental middle cerebral artery occlusion in rats 
We found that thioredoxin level was significantly higher in acute stroke patients compared to control group (p = 0.001).This finding is in accordance with the results of most of the studies which assessed thioredoxin as a marker of oxidative stress in acute ischemic stroke [15, 17, 18].
Similarly, Ozkul, and colleagues  reported that oxidative stress plays a crucial role in the pathogenesis of acute ischemic stroke, and subsequent oxidative damage caused by free radical formation may be factors in stroke severity, while Carbonell and colleagues  found that following ischemic stroke, iron-dependent oxidative stress in the penumbra can enhance necrosis and further neurological deterioration.
On the other hand, Al-Hussain and colleagues  in their study which included 45 acute ischemic stroke patients found no statistically significant difference between serum level of thioredoxin in their acute ischemic stroke patients and control group. The mean age of patients included in this study was 40 ± 16 which is significantly younger than our study population (55.94 ± 12.84). Also, they did not include in their study any data about stroke severity at presentation, type of stroke or volume of infarction, underlying risk factors, or stroke outcome.
We studied the relation between some of the most common modifiable and non-modifiable risk factors of stroke (age, sex, smoking, diabetes mellitus, hypertension, dyslipidemia, and carotid stenosis ≥50%) and thioredoxin level at presentation. Thioredoxin level was significantly higher in hypertensive patients and in patients who had carotid stenosis, ≥50%. Whereas there was no significant relation between thioredoxin level and age, sex, smoking, diabetes mellitus, or dyslipidemia.
Hypertension is considered as one of the most important risk factor for cerebrovascular diseases . Oxidative stress has gained more attention as one of the primary mechanisms responsible for the generation of hypertension. Reactive oxygen species have an important role to play in the homeostasis of the vessel wall. In arteries isolated from hypertensive rats and humans, antioxidant bioactivity is reduced, redox-dependent signaling is enhanced, and ROS production is increased .
In addition, the mechanical stimulation on the vascular wall which increases with hypertension may increase ROS production. ROS-induced vasoconstriction results from reduced nitric oxide (NO) levels and increased intracellular calcium concentration and as a result contributing to the pathogenesis of hypertension .
Carotid artery atherosclerotic disease accounts for a considerable percentage of all strokes . Oxidative stress plays a crucial role in the pathogenesis of atherosclerotic vascular disease .
Studies have demonstrated that oxidative stress is a fundamental feature of the atherogenesis . The redox status occurs when imbalance happens between antioxidant capacity and activity species including reactive nitrogen and halogen species, ROS, non-radical as well as free radical species . This imbalance leads to cell injury by directly oxidizing cellular lipid, protein, and DNA or by initiating cell death signaling pathways .
Moreover, other studies demonstrated that ROS have been implicated in matrix metalloproteinases activation, endothelial dysfunction, and migration of vascular smooth muscle cell . Also, ROS can promote vascular disease by reduction of NO bioavailability resulting in lower antiapoptotic and vasodilator action of NO .
In this study, there was a statistically significant positive correlation between serum level of thioredoxin and stroke severity at presentation measured by NIHSS (r = 0.503 and p = 0.021)
This is in accordance with Qi and colleagues  and Wu and colleagues  studies which also found a significant positive association between serum thioredoxin levels and NIHSS scores.
In contrast, Tieer and colleagues  found negative correlation between NIHSS score at admission and serum thioredoxin levels in their cardioembolic stroke patients.
Also, we found a statistically significant positive correlation between thioredoxin level and volume of infarction measured by MRI (r = 0.551 and p = 0.001). Supporting our results, Nanetti and colleagues  found that changes in the generation of free radicals and as a result oxidative stress may play a role in the pathogenesis and extent of acute ischemic lesions.
This is in accordance with Qi and colleagues’  and Wu and colleagues’  while Tieer and colleagues  found serum thioredoxin levels in patients with small infarction were not significantly different from those in the large infarction volume group.
Regardless of the mechanisms responsible for ischemic stroke, a sequence of events through different pathways increases the production of free radicals. During ischemia, as a result of deficiency of oxygen and glucose substrates, ATP cannot be produced which leads to inactivation of ATP-dependent ion pumps, membranes depolarization, and disturbance in trans membrane ion gradients. As a result, calcium is translocated from extracellular to intracellular spaces, activating cellular lipases and proteases and the subsequent cerebral tissue breakdown .
We found that thioredoxin was significantly higher in patients with poor outcome compared to patients with good outcome. Using ROC curve, the best cutoff limit of thioredoxin levels early after admission (in the first 24 h of stroke) in predicting poor outcome was 21.89 ng/ml (88% sensitivity and 64% specificity). Higher thioredoxin level was found to be significant predictors of bad outcome of stroke (OR and P value of 1.139 and 0.011) using binary logistic regression. We also found a statistically positive correlation between thioredoxin level and clinical outcome after 3 months measured by mRS.
This finding is similar to Qi and colleagues study  which included 312 patients and found that serum thioredoxin levels were higher compared with those in patients with a favorable outcome, while their optimal cutoff value of serum thioredoxin levels as an indicator for prognosis of functional outcome based on the ROC curve was slightly lower than our results, 20.0 ng/ml (82.8% sensitivity and 78.9% specificity).
Also, Wu and colleagues  found that serum thioredoxin levels were higher in patients with unfavorable outcome compared with those in patients with a favorable outcome.
In contrast, Tieer and colleagues  in their study which included 198 acute ischemic stroke patients found that serum thioredoxin levels in the favorable outcome group were significantly higher than in the unfavorable outcome group.
The conflict between the results of our study supported by the results of Qi and colleagues  and Wu and colleagues  on one hand and the results of Tieer and colleagues  on the other hand regarding the relation between thioredoxin level and stroke severity at presentation, volume of infarction, and functional out come after 3 months may be explained by the differences in timing of sampling (onset of symptom within 24 h versus 72 h). The median NIHSS score in our study was 10.6 and in Qi and colleagues’ and Wu and colleagues’ studies was 9 while in Tieer study of the population, the median score was only 4 points. Also, there are different indicators of functional outcome (modified Rankin Scale versus Barthel Index). Another possible cause may be the heterogeneity of patients as 28% of strokes in our study was cardioembolic and in Qi and colleagues’ and Wu and colleagues’ studies was 31.4% while in Tieer study was only 18.7%.
In this study, thioredoxin levels in patients with cardio-embolic stroke was significantly higher than patients with other ischemic stroke subtypes (p value <0.001). Using ROC curve, the best cutoff limit of thioredoxin levels done to patients early after admission in the first 24 h of stroke predicting cardio-embolic stroke was 25.165 ng/ml (85.7 % sensitivity and 66.7% specificity).
Meanwhile, Qi and colleagues  and Wu and colleagues  found that the median thioredoxin levels were significantly greater for large-vessel occlusive than for the other stroke subtype groups (p value = 0.0001). On the other hand, Tieer and colleagues  found no relation between thioredoxin level and different stroke syndromes.
Limitations of this study include the relatively small number of patients due to the limitation of resources and financial issues, and we measured thioredoxin level in serum, not in cerebral spinal fluid. Whether the peripheral thioredoxin levels reflect similar changes in the central nervous system remains uncertain.
Thioredoxin is a single oxidative stress parameter provides only one-sided and partial insights into neuronal dysfunction and death mediated by free radical