An overview of hyperbaric oxygen preconditioning against ischemic stroke

Abstract

Ischemic stroke (IS) has become the second leading cause of morbidity and mortality worldwide, and the prevention of IS should be given high priority. Recent studies have indicated that hyperbaric oxygen preconditioning (HBO-PC) may be a protective nonpharmacological method, but its underlying mechanisms remain poorly defined. This study comprehensively reviewed the pathophysiology of IS and revealed the underlying mechanism of HBO-PC in protection against IS. The preventive effects of HBO-PC against IS may include inducing antioxidant, anti-inflammation, and anti-apoptosis capacity; activating autophagy and immune responses; upregulating heat shock proteins, hypoxia-inducible factor-1, and erythropoietin; and exerting protective effects upon the blood-brain barrier. In addition, HBO-PC may be considered a safe and effective method to prevent IS in combination with stem cell therapy. Although the benefits of HBO-PC on IS have been widely observed in recent research, the implementation of this technique is still controversial due to regimen differences. Transferring the results to clinical application needs to be taken carefully, and screening for the optimal regimen would be a daunting task. In addition, whether we should prescribe an individualized preconditioning regimen to each stroke patient needs further exploration.

Keywords: Antioxidant capacity; Hyperbaric oxygen therapy; Hypoxia-inducible factor-1; Ischemic stroke; Preconditioning; Stem cell.

Fig. 1

Potential mechanism of hyperbaric oxygen preconditioning for ischemic stroke. Abbreviations: HBO, hyperbaric oxygen; HIF-1α, hypoxia-inducible factor-1α; EPO, erythropoietin; EPOR, erythropoietin receptor; P4H, prolyl 4-hydroxylase; NOS, nitric oxide synthase; GLUT1, glucose transporter 1; CysC, Cystatin C; TIMP-1, tissue inhibitor of metalloproteinases-1; IL-6, interleukin-6; IL-1β, interleukin-1β; MMP9, matrix metalloproteinase-9; TNF-α, tumor necrosis factor-α; SIRT1, Sirtuin 1; HMGB1, High mobility group box 1; CytoC, Cytochrome C; CASP3, caspase3; ROS, reactive oxygen species; AMPK, AMP-activated protein kinase; PI3K/AKT, phosphoinositide 3-kinase/Akt; BDNF, brain-derived neurotrophic factor; NF-κB, nuclear factor kappa-B; MAPK, mitogen-activated protein kinase; HSPs, heat shock proteins; Nrf2, NF-E2-related factor 2; PPAR γ, peroxisome proliferator-activated receptors γ; OGD, oxygen-glucose deprivation; 15d-PGJ2, 15- deoxy-Δ12,14-PGJ2; COX-2, Cyclooxygenase-2; p70 S6 K, ribosomal protein S6 kinase; JAK-2, Janus tyrosine kinase-2; PKB, protein kinase B; STAT5, Signal transducer and activator of transcription 5; PI3-K, phosphatidylinositol-3-kinase; H₂O₂, hydrogen peroxide; SOD, superoxide dismutase; G6PD, glucose-6-phosphate dehydrogenase; HO-1, heme oxygenase-1; GST, glutathione-S transferase; CAT, Catalase; ARE, antioxidant response element.