Neuronal re-organization and functional recovery following activity dependent BDNF upregulation

Object.本研究证明，重复经颅磁刺激（rTMS）诱导缺血耐受后，海马神经元的迟发性神经元死亡（DND），否则致命的缺血insult. Methods。在成年沙鼠短暂（5 min）缺血发作前的不同时间给予不同方案的rTMS。双侧颈总动脉闭塞（BCCO）。在短暂性脑缺血发作后7天定量评估海马CA 1区迟发性神经元死亡的程度，我们将评估当在BCCO前2-5天给予rTMS时，迟发性神经元死亡是否会如缺血耐受中所报道的那样显著减轻。我们将评估在BCCO前2天刺激的动物组中BDNF上调的神经保护程度，rTMS预处理组中CA 1区的神经元密度是否显著高于仅缺血组。当在BCCO之前3、4或5天递送刺激时，将看到类似程度的神经元保留。rTMS的有效性进行了评价，无论是在25和50 Hz的频率刺激。我们还将评估25 Hz刺激128秒（3200个脉冲）是否比50 Hz刺激64秒（3200个脉冲）或128秒（6400个脉冲）更有效。临床应用将在获得伦理委员会批准的硬件规格后进行。

Object. The present study demonstrates that repetitive transcranial magnetic stimulation (rTMS) induces ischemic tolerance against delayed neuronal death (DND) of hippocampal neurons following an otherwise lethal ischemic insult.Methods. Various regimens of rTMS were delivered to adult gerbils at various times prior to an episode of ischemia induced by transient(5min.) bilateral common carotid artery occlusion(BCCO). The extent of delayed neuronal death in the CA1 region of the hippocampus was assessed quantitatively 7 days after the transient ischemic episode.We will evaluate whether when rTMS will delivered 2-5 days prior to BCCO, delayed neuronal death will be substantially attenuated as reported in ischemic tolerance. We will evaluate the degree of neuroprotection by BDNF upregulation in the animals in the group that was stimulated 2 days prior to BCCO, whether neuron density in the CA1 sector was significantly higher in the rTMS pretreatment group than in the ischemia-only group. A similar degree of neuron sparing will be seen when stimulation was delivered 3, 4, or 5 days prior to BCCO. Effectiveness of rTMS was evaluated whether when stimulation was delivered at frequencies of 25 and 50 Hz. We will also evaluate whether stimulation at 25 Hz stimulation for 128 seconds(3200 pulses) is more effective than stimulation at 50 Hz for 64 seconds(3200 pulses) or 128 seconds(6400 pulses). Clinical application will be performed after hardware spec-up with ethical committee approve.