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Repetitive transcranial magnetic stimulation (rTMS) has increasingly been studied over the past decade to determine whether it has a therapeutic benefit on focal cerebral ischemia. However, the underlying mechanism of rTMS in this process remains unclear. In the current study, we investigated the effects of rTMS on the proliferation of adult neural stem cells (NSCs) and explored microRNAs (miRNAs) that were affected by rTMS. Our data showed that 10 Hz rTMS significantly increased the proliferation of adult NSCs after focal cerebral ischemia in the subventricular zone (SVZ), and the expression of miR-25 was obviously up-regulated in the ischemic cortex after rTMS. p57, an identified miR-25 target gene that regulates factors linked to NSC proliferation, was also evaluated, and it exhibited down-regulation. To further verify the role of miR-25, rats were injected with a single dose of antagomir-25 and were subjected to focal cerebral ischemia followed by rTMS treatment. The results confirmed that miR-25 could be repressed specifically and could drive the up-regulation of its target gene (p57), which resulted in the inhibition of adult NSC proliferation in the SVZ after rTMS. Thus, our studies strongly indicated that 10 Hz rTMS can promote the proliferation of adult NSCs in the SVZ after focal cerebral ischemia by regulating the miR-25/p57 pathway.

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Cognitive impairment is a serious mental deficit caused by stroke that can severely affect the quality of a survivor's life. Repetitive transcranial magnetic stimulation (rTMS) is a well-known rehabilitation modality that has been reported to exert neuroprotective effects after cerebral ischemic injury. In the present study, we evaluated the therapeutic efficacy of rTMS against post-stroke cognitive impairment (PSCI) and investigated the mechanisms underlying its effects in a middle cerebral artery occlusion (MCAO) rat model. The results showed that rTMS ameliorated cognitive deficits and tended to reduce the sizes of cerebral lesions. In addition, rTMS significantly improved cognitive function via a mechanism involving increased neurogenesis and decreased apoptosis in the ipsilateral hippocampus. Moreover, brain-derived neurotrophic factor (BDNF) and its receptor, tropomyosin-related kinase B (TrkB), were clearly upregulated in ischemic hippocampi after treatment with rTMS. Additionally, further studies demonstrated that rTMS markedly enhanced the expression of the apoptosis-related B cell lymphoma/leukemia gene 2 (Bcl-2) and decreased the expression of the Bcl-2-associated protein X (Bax) and the number of TUNEL-positive cells in the ischemic hippocampus. Both protein levels and mRNA levels were investigated. Our findings suggest that after ischemic stroke, treatment with rTMS promoted the functional recovery of cognitive impairments by inhibiting apoptosis and enhancing neurogenesis in the hippocampus and that this mechanism might be mediated by the BDNF signaling pathway.

Objective: To investigate the effectiveness of mirror therapy combined with neuromuscular electrical stimulation in promoting motor recovery of the lower limbs and walking ability in patients suffering from foot drop after stroke. Design: Randomized controlled study. Setting: Inpatient rehabilitation center of a teaching hospital. Subjects: Sixty-nine patients with foot drop. Intervention: Patients were randomly divided into three groups: control, mirror therapy, and mirror therapy + neuromuscular electrical stimulation. All groups received interventions for 0.5 hours/day and five days/week for four weeks. Main measures: 10-Meter walk test, Brunnstrom stage of motor recovery of the lower limbs, Modified Ashworth Scale score of plantar flexor spasticity, and passive ankle joint dorsiflexion range of motion were assessed before and after the four-week period. Results: After four weeks of intervention, Brunnstrom stage (P = 0.04), 10-meter walk test (P < 0.05), and passive range of motion (P < 0.05) showed obvious improvements between patients in the mirror therapy and control groups. Patients in the mirror therapy + neuromuscular electrical stimulation group showed better results than those in the mirror therapy group in the 10-meter walk test (P < 0.05). There was no significant difference in spasticity between patients in the two intervention groups. However, compared with patients in the control group, patients in the mirror therapy + neuromuscular electrical stimulation group showed a significant decrease in spasticity (P < 0.001). Conclusion: Therapy combining mirror therapy and neuromuscular electrical stimulation may help improve walking ability and reduce spasticity in stroke patients with foot drop.

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Background Electroacupuncture (EA) has been commonly used to treat stroke in China. However, the underlying mechanism remains largely unknown. The present study investigated the neuroprotective effects of EA in middle cerebral artery occlusion (MCAO) rats and elucidated the possible anti-inflammatory mechanisms. Material/Methods In this study, modified neurological severity scoring (mNSS) was used to assess neurological deficits, and TTC staining and brain water content were measured to evaluate the degree of brain damage. HE staining, Nissl staining, and TUNEL staining were employed to evaluate apoptotic neuronal death. Molecular biological methods were used to measure the levels of miR-233, NLRP3, caspase-1, IL-1β, and IL-18 in the peri-infarct cortex. Results Our results showed that EA treatment significantly decreased the neurological deficit score and infarct volume of MCAO rats. The level of miR-223 was increased, while the levels of NLRP3, caspase-1, IL-1β, and IL-18 were decreased in the peri-infarct cortex of EA-treated MCAO rats. However, the neuroprotective effect of EA was partially blocked by antagomir-223. Conclusions These data suggest that EA treatment can alleviate neuroinflammation by inhibiting the miR-223/NLRP3 pathway, thus playing a neuroprotective role in MCAO in rats.

It is well known that extensive osteoclast formation plays a key role in osteoporosis in post-menopausal women and the elderly. The suppression of extensive osteoclastogenesis and bone resorption may be an effective preventive strategy for osteoporosis. Zoledronic acid (ZOL) has been indicated to play an essential role in regulating bone mineral density and has already been used in large clinical trials. However, the effects of ZOL on osteoclastogenesis remain to be fully elucidated. Therefore, the present study aimed to determine the effects of ZOL on osteoclastogenesis, and to explore the corresponding signalling pathways. By using a cell viability assay, as well as in vitro osteoclastogenesis, immunofluorescence and resorption pit assays, we demonstrated that ZOL (0.1-5 µ M) suppressed receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclast differentiation and bone resorptive activity. Furthermore, western blot analysis and reverse transcription-quantitative PCR indicated that ZOL inhibited the RANKL-induced activation of NF-κB and the phosphorylation of JNK in RAW264.7 cells, and subsequently decreased the expression of osteoclastogenesis-associated genes, including calcitonin receptor, tartrate-resistant acid phosphatase and dendritic cell-specific transmembrane protein. ZOL inhibited osteoclast formation and resorption in vitro by specifically suppressing NF-κB and JNK signalling. On the whole, the findings of this study indicate that ZOL may serve as a potential agent for the treatment of osteoclast-associated diseases, including osteoporosis.