SOD3 overexpression alleviates cerebral ischemia‐reperfusion injury in rats

Abstract

BackgroundIschemic stroke is a deadly disease that poses a serious threat to human life. Superoxide dismutase 3 (SOD3, ECSOD) is the main antioxidant enzyme that removes superoxide anions from cells. This study aimed to investigate the effect of SOD3 overexpression on cerebral ischemia‐reperfusion injury in rats.MethodsGV230‐EGFP‐ECSOD, the recombinant SOD3‐overexpressed vector, was constructed by genetic engineering technology, and mesenchymal stem cells (MSCs) were infected with lentiviral packaging. In animal experiment, cerebral ischemia‐reperfusion injury model rats were successfully established. ECSOD‐MSCs are the MSCs that successfully transfected with SOD3 overexpression vector. The animals were injected with ECSOD‐MSCs (ECSOD‐MSC group), normal MSCs (MSCs group), PBS (PBS group), and not do any processing (Model group) via the tail vein. Then MRI was used to detect the infarct volume of rats, modified Neurological Severity Scores (mNSS), and immunohistochemistry were used to evaluate the expression of neurological function and apoptosis‐related genes in rats.ResultsWestern blot analysis revealed that the SOD3 was highly expressed in MSCs. Animal experiments showed that the transplantation of ECSOD‐MSCs significantly reduced the infarct volume of ischemic stroke rats (p < 0.05), significantly improved neurological function in rats (p < 0.05), and found proapoptotic gene, Bax, expression was significantly decreased (p < 0.05), the expression of anti‐apoptotic gene, Bcl‐2, was significantly increased (p < 0.05). The highly expressed SOD3 has no correction with brain infarct volume, and the highly expressed SOD3 has a positive correlation with cell apoptosis. It is speculated that overexpression of SOD3 affects the expression of Bax and Bcl‐2, and improves apoptosis to alleviate ischemic stroke.ConclusionOur results indicated that MSCs transfected with SOD3 can effectively alleviate cerebral ischemia‐reperfusion injury in rats.

The Applications and Mechanisms of Superoxide Dismutase in Medicine, Food, and Cosmetics

“…In the diagnosis or treatment of diseases such as brain injury, reducing the level of SOD2 protein in mouse hippocampal neurons can reduce brain damage caused by hypoxia/reoxygenation. Similarly, SOD3 reduces obesity and inflammation caused by high fat, as well as brain damage due to cerebral ischemia [ 46 , 47 , 48 , 49 ]. These suggested that SOD2 or SOD3 could serve as important reference indicators for brain injury.…”

Improved therapeutics of modified mesenchymal stem cells: an update

“…With an additional scaffold of human BDNF (brain-derived neurotrophic factor) linked to chitosan scaffolds, the modified MSCs adequately migrate to the target site, and induce tissue regeneration within the traumatic brain injury environment [113]. Again, SOD3-MSCs administration do not only reduce the infarct volume of ischemic stroke rats, but also significantly improve the neurological function [114]. The effects of exosomes extracted from hypoxic preconditioned MSCs on memory deficits in Alzheimer disease mice model have also been documented.…”

MSC based gene delivery methods and strategies improve the therapeutic efficacy of neurological diseases

“…Additionally, the overexpression of chemokine (C-X-C motif) receptor 4 (CXCR4) by transient transfection [ 266 ] or stable transfection [ 267 ] in MSCs promoted MSC mobilization and enhanced neuroprotection in a rat cerebral ischemia model [ 266 , 267 ]. Other studies have shown that the overexpression of SOD3 [ 268 ], HGF [ 269 ], IL-10 [ 270 ], CCL2 [ 223 ], NGN1 [ 271 ], NGR1 [ 272 ], TSP4 [ 273 ], ITGA4 [ 274 ], BDNF [ 275 ] and EGFL7 [ 276 ] as well as miR-138-5p [ 277 ] can enhance the immunomodulatory and neuroprotective effects of MSCs and significantly improve the recovery of motor functions when transplanted into a rat stroke model.…”