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Objective@#To observe the effects of paired associative stimulation (PAS) on synaptic ultrastructure, neuron apoptosis and BDNF in rats with cerebral infarct, and explore the possible underlying mechanisms.@*Methods@#Forty-five male Sprague-Dawley rats were randomly divided into three groups: a sham operation group, a model group and a PAS group, with 15 rats in each. All the rats underwent a surgical operation for transient middle cerebral artery occlusion (MCAO) on the right side to model focal cerebral ischemia, with those in the sham operation group left without real occlusion. PAS treatment was given to rats in the PAS group 24h after MCAO model was successfully established, while no special intervention was given to those in the sham operation group and model group. After 28 days of treatment, transmission electron microscopy was used to investigate the ultrastructure of the ischemic penumbra, TUNEL was used to observe the apoptosis of cortex neurons, and real time-PCR to investigate BDNF mRNA expression.@*Results@#It was found that after 28 days treatment: ①The synaptic curvature, the synapse length and the post-synaptic density (PSD) decreased significantly in the rats of model group in contrast to those of the sham control group (P<0.05). And compare to model group, the synaptic curvature, the synapse length and the PSD increased significantly in the rats of PAS group (P<0.05). ②Compare to sham control group, the apoptosis rate of model group and PAS group increased significantly (P<0.05). And the apoptosis rate of PAS group decreased significantly in contrast to those of model group (P<0.05). ③Compare to sham control group, BDNF mRNA expression of the PAS group increased significantly(P<0.05), while BDNF mRNA expression of the model group decreased significantly(P<0.05). BDNF mRNA expression of the PAS group increased significantly in contrast to those of model group (P<0.05).@*Conclusion@#PAS promotes neural plasticity and inhibits apoptosis of cortex neurons of the ischemic penumbra in rats with ischemic cerebral infarction. One of the underlying mechanisms might be related to the up-regulation of BDNF mRNA expression.
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Objective To explore the effects and the underlying mechanisms by which paired associative stimulation ( PAS) of tibial nerve electrostimulation and M1 cortex transcranial magnetic stimulation ( TMS) in pro-moting the recovery of forelimb dysfunction in rats with cerebral ischemic stroke. Methods Resting motor thresholds of left extensor carpi radialis muscle ( ECR) were determined 5 min before and 5 min, 30 min, 60 min after PAS,respectively, in 8 male Sprague-Dawley ( SD) rats. Then 48 male SD rats were divided into a sham group ( n=16) subject to sham surgery, an experimental group (n=32) which was further divided into a MCAO group (n=16) and a PAS group (n=16) after cerebral ischemic stroke model was established successfully by occluding the right middle cerebral artery. 24 hours after surgery, PAS consisting of left tibial nerve stimulation and right M1 cortex area TMS was applied to PAS group once daily for 7 consecutive days. The corner tests and grip strength tests were per-formed before and after 7 days of PAS treatment in each group. The RMTs of left ECR were determined, metabolites of the left area tissue of cervical spinal cord were measured by nuclear magnetic resonance spectrum, and expressions of Bcl-2 and Bax of left and right area tissue of cervical spinal cord enlargement were detected by Western Blot tech-nique after 7 days of intervention. Results The average RMTs of left ECR at 5 min, 30 min, 60 min after PAS were significantly lower than those at 5 min before PAS ( P<0.05) . All rats in experimental group showed significant higher turning scores and lower grip strength when compared with sham group (P<0.001 or P<0.01). After PAS interven-tion, PAS group demonstrated lower turning scores, higher grip strength and lower RMT of left ECR as compared with MCAO group ( P<0.05 or P<0.01) . The expression of GABA of left cervical enlargment was significantly decreased in MCAO group when compared with the sham group ( P<0.05) , and there was no significant difference between MCAO group and PAS group. Meanwhile, other metabolites showed no significant difference among the three groups. The av-erage expression level of Bcl-2 and Bax proteins in both sides of cervical spinal cord enlargment showed no significant difference among three groups either. Conclusions Tibial nerve-M1 cortex area PAS may increase the excitability of motor cortical representation of forelimbs in rats, by which PAS promotes the recovery of forelimb dysfunction in rats with cerebral ischemic stroke.
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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.
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This review intends to synthesize our understanding of the effects of novel approach of non-invasive peripheral nerve and brain stimulation techniques in motor rehabilitation and the potential role of these techniques in clinical practice. The ability to induce cortical plasticity with non-invasive stimulation techniques has provided novel and exciting opportunities for examining the role of the human cortex during a variety of behaviors literature concerning non-invasive stimulation technique incorporated into stroke research is young, limiting the ability to draw consistent conclusions. In this review we discuss how these techniques can enhance the effects of a behavioral intervention and the clinical evidence for its use to date.
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Humanos , Encéfalo , Nervos Periféricos , Plásticos , Reabilitação , Acidente Vascular CerebralRESUMO
Objective To investigate the effects of paired associative stimulation (PAS) on the recovery of upper limb motor function in stroke patients,and to analyze the relationship between the change of motor cortex excitability in the contralesional hemisphere and the recovery of motor function in the affected upper limb.Methods Thirty hemiplegic stroke patients were divided randomly into a treatment group and a control group.Both groups were given routine rehabilitation therapy,but the treatment group also received PAS consisting of transcranial magnetic stimulation (TMS) of the intact motor cortex and electrical stimulation (ES) of the median nerve at the wrist of the intact arm with an interval of 10 ms between the TMS and ES (PAS10).The PAS10 was delivered at a frequency of 0.05 Hz and an intensity of 120％ the resting motor threshold (RMT),once daily for 30 minutes,five times a week for 4 weeks.Corticospinal excitability was measured using motor evoked potentials (MEP) and the RMT.The FuglMeyer upper limb assessment (FMA),Brunnstrom staging and the modified Barthel index (MBI) were also applied before and at the end of the 4 weeks of treatment.Correlation was sought between any changes in MEP amplitude,the RMT of the contralesional hemisphere and changes in the FMA results.Results Before the intervention there were no significant differences between the two groups in terms of any of the assessments.After 4 weeks of treatment,all the assessments had changed significantly compared to those before the treatment,but there were still no significant differences between the two groups in terms of any the assessments.After 4 weeks of treatment,the differences in MEP amplitude from the contra-lesional hemisphere and the differences in FMA scores were positively and significantly correlated with a correlation coefficient of r =0.431.The lesioned hemisphere was also positively correlated with the differences in FMA scores with a significant correlation coefficient of r =0.608.Conclusion PAS10 can facilitate the recovery of upper limb motor function.The change in motor cortex excitability of the contra-lesional hemisphere significantly correlates with functional recovery in the upper limb.
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Objective To compare the effects of paired associative stimulation (PAS) and repetitive transcranial magnetic stimulation (rTMS) on motor cortex excitability.Methods The baseline corticospinal excitability of the left hemispheres of 10 healthy subjects was measured in terms of resting motor threshold (RMT) and other indicators of motor evoked potentials (MEP).On the following day they received PAS composed of trascranial magnetic stimulation (TMS) to the motor cortex of the left hemisphere and electric stimulation (ES) of the median nerve contralateral to the motor cortex,with an interval of 10ms between the TMS and ES (termed PAS10).The PAS10 was delivered at a frequency of 0.05 Hz and an intensity of 120％ of the RMT,for a total of 90 pulses.The MEP amplitude,MEP latency and RMT were evaluated one minute after the stimulation.After the PAS intervention,an interval of one week was allowed to eliminate any effect of PAS on motor cortex excitability.Then rTMS was delivered to the subjects' left motor cortex at the same time of day at a frequency of 1 Hz and an intensity of 120％ of the RMT,for a total of 1000 pulses.MEP amplitude,MEP latency and RMT were evaluated one minute after the stimulation.The two interventions were compared in terms of MEP amplitude,MEP latency and RMT.Results The average MEP amplitude,MEP latency and RMT at baseline were (2.93 ± 0.99) mV,(20.97 ± 1.67) ms,and (46.06 ±5.32) ％,respectively.One minute after PAS10,the MEP amplitude,MEP latency and RMT were (1.14 ± 0.76) mV,(21.87 ± 1.09) ms and (52.06 ±4.20) ％,respectively.One minute after rTMS,the MEP amplitude and latency and the RMT were (2.24 ± 0.79) mV,(20.88 ± 1.94) ms,and (49.00 ± 4.54) ％,respectively.The differences in MEP amplitude,MEP latency and RMT pre-and post-intervention were (0.69 ± 0.10) mV,(0.09 ±0.05) ms and (3.94 ± 0.93) ％,respectively for rTMS.For PAS10 they were (1.83 ± 0.14) mV,(0.90 ± 0.26)ms and (6.00 ± 1.13)％,respectively.The differences in MEP amplitude decrease and MEP latency lengthening between the two stimulation protocols were significant,but the difference in RMT elevation was not.Conclusion Both PAS10 and low frequency rTMS suppressed motor cortex excitability,but the suppressive effect of PAS10 is more significant.