Dissertation
Dissertation > Medicine, health > Neurology and psychiatry > Neurology > Cerebrovascular disease > Acute cerebrovascular disease ( stroke)

The Mechanism of MicroRNAs in the Proliferation of Neural Stem Cells after Transient Focal Ischemia with Repetitive Transcranial Magnetic Stimulation

Author ZhangJingHui
Tutor HuangXiaoLin
School Huazhong University of Science and Technology
Course Rehabilitation Medicine and Physical Therapy
Keywords repetitive transcranial magnetic stimulation transient focal cerebral ischemia motor-sensory function neural stem cellrepetitive transcranial magnetic stimulation miR-106b miR-93 miR-25repetitive transcranial magnetic stimulation focal transient cerebral ischemia microRNAmicroarray bioinformatics
CLC R743.3
Type PhD thesis
Year 2012
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ObjectiveRepetitive transcranial magnetic stimulation (rTMS) is a potential non-invasiveneurostimulatory technique used in the therapy for cerebral ischemia. Despite itsgrowing popularity, basic molecular mechanisms underlying the clinical effects ofrTMS have remained largely under-researched. rTMS promotes the neural stemcell(NSC) proliferation after stroke. The frequency of rTMS determines the directionof neural excitation. Here we study the effect of the different rTMS frequency on theNSC proliferation in the brain of rats subjected to transient focal cerebral ischemia.MethodsSprague-Dawley rats subjected to transient middle cerebral artery occlusion(tMCAO) were reperfused for7days or14days. The motor-sensory functions wereassessed everyday.The NSC proliferations in the ipsilateral and contralateralsubventricular zones were also evaluated. Repeated-measured ANOVA and two wayANOVA were used respectively.ResultsWithin14days after cerebral ischemia, all the motor-sensory functions improvedover time. In the postural signs and the symmetry of muscle strength and muscle tone,both10Hz and1Hz rTMS group improved faster than model group on5d and7d. TheNSC proliferations in SVZ of both sides were significantly promoted by10Hz rTMS on7d, compared with other three groups. On14d after tMCAO, the NSCproliferations were increased in1Hz and5Hz groups compared with model group.The NSC proliferation significantly decreased in10Hz group on14d compared withthat on7d.ConclusionBoth1Hz and10Hz rTMS can promote motor-sensory function in rats aftertransient focal cerebral ischemia. But the effects have a short duration. rTMS withlow and high frequencies can promote NSC proliferation. The effect of10Hz rTMSmay be only significant in short duration, and that of lower frequencies may beweaker but last longer. ObjectiveRepetitive transcranial magnetic stimulation promotes the proliferation of adultneural stem cell(aNSC) after cerebral ischemia. Mir-106b family is an essentialregulator of the aNSC proliferation. Here we study the importance of mir-106b familyin the brain of rats subjected to transient focal cerebral ischemia with rTMS.MethodsSprague-Dawley rats subjected to tMCAO were reperfused for7days, andipsilateral forebrain samples were harvested. The expressions of miR-106b familywere determined by real-time PCR.ResultsThe increased expression of miR-25in the forebrain of the ischemic cerebralhemisphere was detected at7d after ischemia. Compared with sham group and modelgroup, the expression of three members of miR-106b family significantly increased inthe treatment of rTMS.ConclusionThe results suggest that mir-106b family may be an important effector of rTMSto promote the aNSC proliferation after cerebral ischemia. ObjectiveMicroRNAs are noncoding RNAs that control cellular function by eitherdegrading mRNAs or arresting their translation. To understand their functionalsignificance in the treatment of repetitive trancranial magnetic stimulation(rTMS), weprofiled miRNAs in adult rat brain after transient middle cerebral artery occlusionwith rTMS.MethodsSprague-Dawley rats subjected to tMCAO were reperfused for7days, andipsilateral striatum samples were harvested. miRNA microarray were carried out, andthe data were validated by quantitative real-time polymerase chain reaction andanalysed in bioinformatic methods.ResultsWe report here for the first time the involvement of miRNA regulation incerebral ischemic pathogenesis associated with repetitive transcranial magneticstimulation.15miRNAs were related to ischemia, and3of them were changed afterrTMS.20miRNAs were only related to rTMS at7d after ischemia. Bioinformaticsanalysis indicated a correlation between miRNAs altered to several mRNAs known tomediate response to stimulation, growth, development, cellular metabolism andlocolization. Four significant related signaling pathways were indicated as well,including Wnt signaling pathway, insulin pathway, regulation of actin cytoskeleton and tight junction. miR-743b,miR-294and miR-137were indicated as importantmiRNAs in the mechanism of rTMS.CONCLUSIONS:Further studies are needed to evaluate the possible use of miRNAs as the effectorof rTMS in stroke patients.

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