Transcranial direct current stimulation promotes hippocampal neurogenesis in mice with cerebral ischemia involving up-regulation of nmda receptors / 中国药理学通报

ABSTRACT

Aim To investigate the improving effect of transcranial direct current stimulation (tDCS) on endogenous hippocampal neurogenesis in mice with cerebral ischemiaand the possible mechanism. Methods The model of acute cerebral ischemia in mice was established by bilateral common carotid artery occlision (BCCAO). The pathological changes of mice were detected by hippocampal HE staining. The learning and memory function of mice was assessed by Morris water maze. The number of BrdU, DCX and BrdU/NeuN-positive cells was observed through immunofluorescence staining for detecting hippocampal neurogenesis. The mRNA and protein expressions of NMDAR subunits NR2a and NR2b in hippocampus were detected by qRT-PCR and Western blot. Results The neuronal damage in the hippocampal CA1 region was marked (P <0. 01), and the learning and memory function significantly decreased (P<0. 01) in cerebral ischemia mice, suggesting the successful establishment of cerebral ischemia model. At the same time, the number of BrdU, DCX and BrdU/NeuN positive cells was up-reg-ulated significantly (P < 0. 01 ) , indicating the occurrence of neurogenesis in hippocampus after cefebral ischemia. Treatment with tDCS significantly ameliorated the pathological damage in CA1 region of mice, improved learning and memory, and promoted hippocam-pal neurogenesis. Meanwhile, the mRNA and protein expression levels of NR2a and NR2b in hippocampus were also up-regulated (P < 0. 05 or P < 0.01). Conclusions tDCS can promote hippocampal neurogenesis and improve learning and memory function in cerebral ischemia mice, which may be related to theup-regula-tion ofNR2a and NR2b expression.