Recombinant human thioredoxin-1 promotes neurogenesis and facilitates cognitive recovery following cerebral ischemia in mice

摘要: Cerebral ischemia (CI) can induce loss of hippocampal neurons, causing cognitive dysfunction such as learning and memory deficits. In adult mammals, the dentate gyrus contains neural stem cells (NSCs) that continuously generate newborn neurons integrate into pre-existing networks throughout life, which may ameliorate following CI. Recent studies have demonstrated recombinant human thioredoxin-1 (rhTrx-1) could promote proliferation adipose tissue-derived mesenchymal angiogenesis. To investigate whether rhTrx-1 also regulates neurogenesis CI its underlying mechanisms, mice were subjected to bilateral common carotid arteries occlusion (BCCAO) treated with before reperfusion. Mice showed shortened escape latencies in Morris water maze by 30 days improvements spatial probe trial test. Enhanced NSCs was observed at day 14, indicated BrdU Ki67 immunostaining. Doublecortin (DCX)(+) significantly increased treatment. Despite increases BrdU(+)/NeuN(+) 30, double-labeling total BrdU(+) ratio not affected The promotive effects on differentiation further confirmed vitro assays. Western blot revealed ERK1/2 phosphorylation after treatment, ERK inhibitor U0126 abrogated proliferation. These results provide initial evidence through signaling pathway are beneficial for improving global