Objective To observe the effect of paired associative stimulation ( PAS) on the recovery of sensorimotor function and to explore the mechanism in terms of neural plasticity. Methods Ninety male adult Sprague-Dawley rats were randomly divided into a sham operation group (Sham group), a model group (Model group) and a paired associative stimulation group ( PAS group) , each of 30. Each group was then subdivided into 7-, 14-and 28-day subgroups with 10 rats in each. A model of focal cerebral ischemia and reperfusion was estab-lished using the Longa suture method in the Model and PAS groups. The rats in the Sham group underwent the same surgical procedure except for the occlusion of the middle cerebral artery. The rats received 30 minutes of paired pe-ripheral nerve stimulation and transcranial magnetic stimulation comprising 90 pairs at 0.05 Hz beginning 24 h after the occlusion. The impulse wave width of the peripheral nerve stimulation was 200 μs and the intensity was 6 mA. The intensity of the transcranial magnetic stimulation was 120％ of the resting motor threshold. The other two groups weren't given any intervention. Neurological function was tested using Garcia scores on the 1st, 7th, 14th and 28th day after surgery. The rats were then sacrificed and the expression of MAP-2 and GAP-43 in the ischemic penumbra were detected using western blotting and immunohistochemistry. Results No neurological dysfunction was ob-served in the Sham group at any time. Compared with the Sham group at the same time points, the average Garcia scores of the Model and PAS groups were significantly lower (P≤0.05). However, the average Garcia scores on the 7th, 14th and 28th day were significantly higher in the PAS group compared with the Model group at the same time points ( P≤0.05) . The average Garcia scores of the Model and PAS groups on the 28th day after surgery were significantly higher than those on the 1st day (P≤0.05), but only the PAS group's average Garcia score on the 28th day was significantly higher than that on the 7th day. Compared with the Sham group at the same time points, the expression of MAP-2 and GAP-43 protein in the Model and PAS groups was significantly higher, but with that of the Model group significantly lower than that of the PAS group ( all P≤0.05) . The protein expression of MAP-2 and GAP-43 protein in the PAS group on the 14th day was significantly higher than on the 7th and 28th day ( P≤0.05 for both) . Conclusions PAS can promote the recovery of sensorimotor function after cerebral thrombosis, at least in rats. That may be due to its promoting the expression of the neuroplasticity-associated proteins MAP-2 and GAP-43 in the ischemic penumbra.%目的 观察成对关联刺激(PAS)对局灶性脑缺血再灌注大鼠感觉运动功能恢复的影响,并从神经可塑性角度探讨其可能的作用机制.方法 选取90只健康雄性SD大鼠,随机分为假手术组、模型组和PAS组,每组又分为7 d、14 d、28 d 3个亚组,每组10只.模型组和PAS组大鼠采用Longa线栓法制作大脑中动脉栓塞(MCAO)模型,假手术组除不插入线栓外,其余操作与模型组和PAS组相同.PAS组于术后第1天开始给予0.05 Hz、共90对脉冲的PAS治疗[其中周围神经电刺激(PNS)脉冲波宽200μs、刺激强度6 mA;经颅磁刺激(TMS)强度120％静息运动阈值(RMT)],持续30 min,每日1次;模型组和假手术组不予任何干预措施.术后第1、7、14、28天采用Garcia神经行为学评分评定大鼠感觉运动功能,各时间点治疗结束后,采用免疫组化和蛋白质印记法(Western blot)检测大鼠缺血半暗带区微管相关蛋白-2(MAP-2)、生长相关蛋白43(GAP-43)的表达.结果 假手术组大鼠在各时间点均无神经功能损伤的体征.与假手术组同时间点比较,模型组、PAS组Garcia神经功能评分均较低(P<0.05).与模型组同时间点比较,PAS组术后7 d、14 d、28 d的Garcia神经功能评分均较高(P<0.05).与组内术后1 d比较,模型组、PAS组术后28 d的Garcia神经功能评分显著较高(P<0.05).与组内术后7 d比较,仅PAS组术后28 d的Garcia神经功能评分较高(P<0.05).与假手术组同时间点比较,模型组、PAS组GAP-43蛋白表达水平较高(P<0.05),MAP-2蛋白表达水平较低(P<0.05).与模型组同时间点比较,PAS组GAP-43、MAP-2蛋白表达水平较高(P<0.05).与组内术后7 d比较,PAS组术后14 d GAP-43、MAP-2蛋白表达水平较高(P<0.05).与组内术后14 d比较,PAS组术后28 d GAP-43、MAP-2蛋白表达水平降低(P<0.05).结论 PAS可促进缺血性脑卒中大鼠感觉运动功能的恢复,其机制可能与促进缺血半暗带区MAP-2、GAP-43的表达有关.
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