Do Concentration or Activity of Selenoproteins Change in Acute Stroke Patients? A Systematic Review and Meta-Analyses

Abstract

Introduction: Stroke is characterized by deleterious oxidative stress. Selenoprotein enzymes are essential endogenous antioxidants, and detailed insight into their role after stroke could define new therapeutic treatments. This systematic review aimed to elucidate how blood selenoprotein concentration and activity change in the acute phase of stroke. Methods: We searched PubMed, EMBASE, and Medline databases for studies measuring serial blood selenoprotein concentration or activity in acute stroke patients or in stroke patients compared to non-stroke controls. Meta-analyses of studies stratified by the type of stroke, blood compartment, and type of selenoprotein measurement were conducted. Results: Eighteen studies and data from 941 stroke patients and 708 non-stroke controls were included in this review. Glutathione peroxidase (GPx) was the only identified selenoprotein, and its activity was most frequently measured. Results from 12 studies and 693 patients showed that compared to non-stroke controls in acute ischaemic stroke patients, the GPx activity increased in haemolysate (standardized mean difference [SMD]: 0.27, 95% CI: 0.07–0.47) but decreased in plasma (mean difference [MD]: −1.08 U/L, 95% CI: −1.94 to −0.22) and serum (SMD: −0.54, 95% CI: −0.91 to −0.17). From 4 identified studies in 106 acute haemorrhagic stroke patients, the GPx activity decreased in haemolysate (SMD: −0.40, 95% CI: −0.68 to −0.13) and remained unchanged in plasma (MD: −0.10 U/L, 95% CI: −0.81 to 0.61) and serum (MD: −5.00 U/mL, 95% CI: −36.17 to 26.17) compared to non-stroke controls. Results from studies assessing the GPx activity in the haemolysate compartment were inconsistent and characterized by high heterogeneity. Conclusions: Our results suggest a reduction of the blood GPx activity in acute ischaemic stroke patients, a lack of evidence regarding a role for GPx in haemorrhagic stroke patients, and insufficient evidence for other selenoproteins.

Selenium, Stroke, and Infection: A Threefold Relationship; Where Do We Stand and Where Do We Go?

“…A broad concept for the underlying mechanism may be micronutrient depletion, as cells mobilize antioxidants such as GPx to survive both their own hypermetabolic states and the pro-oxidant milieu [ 94 ]. In a murine stroke model, adequate GPx scavenging limited hypoxic and ischemia-reperfusion injury [ 95 ]; this model may be applicable to stroke patients, where a reduction of glutathione peroxidase but not other selenoproteins is noted [ 96 ]. Within this context, a prior or concomitant infection could lead to selenium depletion, a concomitant depletion of the selenium-dependent glutathione peroxidase, and the abrogation of their neuroprotection.…”