Effects of a novel regimen of repetitive transcranial magnetic stimulation (rTMS) on neural remodeling and motor function in adult male mice with ischemic stroke.

Neuroinflammation caused by excessive microglial activation plays a key role in the pathogenesis of ischemic stroke. Repetitive transcranial magnetic stimulation (rTMS) is a noninvasive neuromodulatory technique that has recently been reported to regulate microglial functions and exert anti-inflammatory effects. The intermittent burst stimulation (iTBS) regimen in rTMS improves neuronal excitability. However, whether iTBS exerts its anti-inflammatory effects by stimulating neurons and thereby modulating microglial polarization remains unclear. Motor function was assessed after 1 week of rTMS (iTBS regimen) treatment in adult male mice with occlusion/reperfusion of the middle cerebral artery (MCAO/r) injury. We also investigated the molecular biological alterations associated with microglial polarization using a cell proliferation assay, multiplex cytokine bioassays, and immunofluorescence staining. iTBS regimen can improve balance and motor coordination function, increase spontaneous movement, and improve walking function in mice with early cerebral ischemia injury. Expression levels of IL-1ß, TNF-α, and IL-10 increased significantly in mice with MCAO injury. Especially, rTMS significantly increased the number of proliferating cells in the infarcted cortex. The fluorescence intensity of MAP2 in the peri-infarct area of MCAO injured mice was low, but the signal was broader. Compared with MCAO group, the fluorescence intensity of MAP2 in rTMS group was significantly increased. rTMS inhibited pro-inflammatory M1 activation (Iba1+/CD86+) and improved anti-inflammatory M2 activation (Iba1+/CD206+) in the peri-infarct zone, thus significantly changing the phenotypic ratio M1/M2. rTMS improves motor dysfunction and neuroinflammation after cerebral I/R injury in mice by regulating microglial polarization.

MiR-34-a acts as a suppressor in neuroblastoma progression by targeting CD44.

OBJECTIVE: To verify whether micro ribonucleic acid 34-a can exert its negative effects in human neuroblastoma cells. METHODS: The study was conducted at The Affiliated Hospital of Qingdao University, Qingdao, Shandong, China during 15 months (from March 2015 to about June 2016). Quantitative reverse transcription polymerase chain reaction was used to find the differences of micro ribonucleic acid 34-a between metastatic neuroblastoma and primary tumours. We transfected micro ribonucleic acid 34-a mimics and antisense oligonucleotides into neuroblastoma cell line to explore its function in vitro through the variations. Additionally, fluorescent reporter assay was used to clear the targeting site of micro ribonucleic acid 34-a and CD44. Furthermore, protein levels of CD44, the putative target gene of micro ribonucleic acid 34-a, was assessed after transfection by Western blot. RESULTS: Compared to the primary neuroblastoma tumours, micro ribonucleic acid 34-a was lower in metastatic neuroblastoma using quantitative reverse transcription polymerase chain reaction (p<0.05). Transfection of micro ribonucleic acid 34-a mimics and antisense oligonucleotides into a neuroblastoma cell line significantly affected cellular activity, migration and invasion (p<0.05_. Fluorescent reporter assays proved that CD44 acts as the target spot of micro ribonucleic acid 34-a for repression in post-transcription level. Micro ribonucleic acid 34-a inhibited the expression of CD44, and increased concentration of micro ribonucleic acid 34-a mimics resulted in a greater decrease in the expression of CD44. CONCLUSIONS: Micro ribonucleic acid 34-a might suppress the progression of neuroblastoma through inhibiting the expression of the potential target gene CD44.