Outcomes and efficacy of magnetic resonance imaging-compatible sacral nerve stimulator for management of fecal incontinence: A multi-institutional study

BACKGROUND Fecal incontinence(FI)is an involuntary passage of fecal matter which can have a significant impact on a patient’s quality of life.Many modalities of treatment exist for FI.Sacral nerve stimulation is a well-established treatment for FI.Given the increased need of magnetic resonance imaging(MRI)for diagnostics,the In-terStim which was previously used in sacral nerve stimulation was limited by MRI incompatibility.Medtronic MRI-compatible InterStim was approved by the United States Food and Drug Administration in August 2020 and has been widely used.AIM To evaluate the efficacy,outcomes and complications of the MRI-compatible InterStim.METHODS Data of patients who underwent MRI-compatible Medtronic InterStim placement at UPMC Williamsport,University of Minnesota,Advocate Lutheran General Hospital,and University of Wisconsin-Madison was pooled and analyzed.Patient demographics,clinical features,surgical techniques,complications,and outcomes were analyzed.Strengthening the Reporting of Observational studies in Epidemiology(STROBE)cross-sectional reporting guidelines were used.RESULTS Seventy-three patients had the InterStim implanted.The mean age was 63.29±12.2 years.Fifty-seven(78.1%)patients were females and forty-two(57.5%)patients had diabetes.In addition to incontinence,overlapping symptoms included diarrhea(23.3%),fecal urgency(58.9%),and urinary incontinence(28.8%).Fifteen(20.5%)patients underwent Peripheral Nerve Evaluation before proceeding to definite implant placement.Thirty-two(43.8%)patients underwent rechargeable InterStim placement.Three(4.1%)patients needed removal of the implant.Migration of the external lead connection was observed in 7(9.6%)patients after the stage I procedure.The explanation for one patient was due to infection.Seven(9.6%)patients had other complications like nerve pain,hematoma,infection,lead fracture,and bleeding.The mean follow-up was 6.62±3.5 mo.Sixty-eight(93.2%)patients reported significant improvement of symptoms on follow-up evaluation.CONCLUSION This study shows promising results with significant symptom improvement,good efficacy and good patient outcomes with low complication rates while using MRI compatible InterStim for FI.Further long-term follow-up and future studies with a larger patient population is recommended.

Repetitive magnetic stimulation affects the microenvironment of nerve regeneration and evoked potentials after spinal cord injury

Repetitive magnetic stimulation has been shown to alter local blood flow of the brain, excite the corticospinal tract and muscle, and induce motor function recovery. We established a rat model of acute spinal cord injury using the modified Allen＇s method. After 4 hours of injury, rat models received repetitive magnetic stimulation, with a stimulus intensity of 35% maximum output intensity, 5-Hz frequency, 5 seconds for each sequence, and an interval of 2 minutes. This was repeated for a total of 10 sequences, once a day, 5 days in a week, for 2 consecutive weeks. After repetitive magnetic stimulation, the number of apoptotic cells decreased, matrix metalloproteinase 9/2 gene and protein expression decreased, nestin expression increased, somatosensory and motor-evoked potentials recovered, and motor function recovered in the injured spinal cord. These findings confirm that repetitive magnetic stimulation of the spinal cord improved the microenvironment of neural regeneration, reduced neuronal apoptosis, and induced neuroprotective and repair effects on the injured spinal cord.

Effect of the combination of high-frequency repetitive magnetic stimulation and neurotropin on injured sciatic nerve regeneration in rats

Repetitive magnetic stimulation is effective for treating posttraumatic neuropathies following spinal or axonal injury.Neurotropin is a potential treatment for nerve injuries like demyelinating diseases.This study sought to observe the effects of high-frequency repetitive magnetic stimulation,neurotropin and their combined use in the treatment of peripheral nerve injury in 32 adult male Sprague-Dawley rats.To create a sciatic nerve injury model,a 10 mm-nerve segment of the left sciatic nerve was cut and rotated through 180°and each end restored continuously with interrupted sutures.The rats were randomly divided into four groups.The control group received only a reversed autograft in the left sciatic nerve with no treatment.In the high-frequency repetitive magnetic stimulation group,peripheral high-frequency repetitive magnetic stimulation treatment(20 Hz,20 min/d)was delivered for 10 consecutive days after auto-grafting.In the neurotropin group,neurotropin therapy(0.96 NU/kg per day)was administrated for 10 consecutive days after surgery.In the combined group,the combination of peripheral high-frequency repetitive magnetic stimulation(20 Hz,20 min/d)and neurotropin(0.96 NU/kg per day)was given for 10 consecutive days after the operation.The Basso-Beattie-Bresnahan locomotor rating scale was used to assess the behavioral recovery of the injured nerve.The sciatic functional index was used to evaluate the recovery of motor functions.Toluidine blue staining was performed to determine the number of myelinated fibers in the distal and proximal grafts.Immunohistochemistry staining was used to detect the length of axons marked by neurofilament 200.Our results reveal that the Basso-Beattie-Bresnahan locomotor rating scale scores,sciatic functional index,the number of myelinated fibers in distal and proximal grafts were higher and axon lengths were longer in the high-frequency repetitive magnetic stimulation,neurotropin and combined groups compared with the control group.These measures were not significantly different among the high-frequency repetitive magnetic stimulation,neurotropin and combined groups.Therefore,our results suggest that peripheral high-frequency repetitive magnetic stimulation or neurotropin can promote the repair of injured sciatic nerves,but their combined use seems to offer no significant advantage.This study was approved by the Animal Ethics Committee of the Affiliated Changzhou No.2 People’s Hospital of Nanjing Medical University,China on December 23,2014(approval No.2014keyan002-01).

A Comparative Study of the Effects of Magnetic Stimulation and Electric Stimulation on Peripheral Nerve Injury in Rat

The influence of pulsed magnetic stimulation on the sciatic nerve injury was investigated. Thirty rats were divided into three groups equally: MS group , electric stimulation group and the control group . The MS and ES were applied immediately after the first 10 min of the sciatic nerve crush. Sciatic function index , toe spreading reflex , muscular weight and volume were measured after the experiment. The TSR of in the groups A and B occurred at 4th day while in the control group it occurs at 10th day. There was statistically significant difference in SFI between groups A and B . The weight and volume of the gastrocnemius muscle were statistically greater in the groups A and B than in the control group . The effect of MS was similar to that of ES. It was suggested that the application of MS immediately after the nerve injury might have an important clinical value as it can accelerate functional recovery and prevent or minimize muscle atrophy. The technique is easily to operate, non invasion, painless and permits tolerance of high intensity output to be used.

Combined Sacral Nerve Roots Stimulation and Low Thoracic Spinal Cord Stimulation for the Treatment of Chronic Pelvic Pain

Some pelvic pain syndromes are very resistant to medical treatment. Several studies have demonstrated that sacral neuromodulation, which has been successfully used for the treatment of bladder dysfunction, incontinence, urinary retention and urinary frequency [1]-[3], can be successfully used for the treatment of chronic pelvic pain [4]-[7]. Several studies have also demonstrated significant involvement of dorsal column pathways in the transmission of visceral pelvic pain [8] and the successful use of spinal cord stimulation for the treatment of chronic pelvic pain [9]. We report three cases of severe chronic pelvic pain that failed conservative treatment modalities. Placement of a combined sacral nerve roots stimulator and a low thoracic spinal cord stimulator resulted in a significant pain relief and improvement in daily life activities. We believe that this combination may help patients suffering from chronic pelvic pain resistant to medical management.

Effects of different frequencies of repetitive transcranial magnetic stimulation on the recovery of upper limb motor dysfunction in patients with subacute cerebral infarction

Studies have confirmed that low-frequency repetitive transcranial magnetic stimulation can decrease the activity of cortical neurons, and high-frequency repetitive transcranial magnetic stimulation can increase the excitability of cortical neurons. However, there are few studies concerning the use of different frequencies of repetitive transcranial magnetic stimulation on the recovery of upper-limb motor function after cerebral infarction. We hypothesized that different frequencies of repetitive transcranial magnetic stimulation in patients with cerebral infarction would produce different effects on the recovery of upper-limb motor function. This study enrolled 127 patients with upper-limb dysfunction during the subacute phase of cerebral infarction. These patients were randomly assigned to three groups. The low-frequency group comprised 42 patients who were treated with 1 Hz repetitive transcranial magnetic stimulation on the contralateral hemisphere primary motor cortex （M1）. The high-frequency group comprised 43 patients who were treated with 10 Hz repetitive transcranial magnetic stimulation on ipsilateral M1. Finally, the sham group comprised 42 patients who were treated with 10 Hz of false stimulation on ipsilateral M1. A total of 135 seconds of stimulation was applied in the sham group and high-frequency group. At 2 weeks after treatment, cortical latency of motor-evoked potentials and central motor conduction time were significantly lower compared with before treatment. Moreover, motor function scores were significantly improved. The above indices for the low- and high-frequency groups were significantly different compared with the sham group. However, there was no significant difference between the low- and high-frequency groups. The results show that low- and high-frequency repetitive transcranial magnetic stimulation can similarly improve upper-limb motor function in patients with cerebral infarction.

Effects of repetitive transcranial magnetic stimulation on cognitive function and cholinergic activity in the rat hippocampus after vascular dementia

Repetitive transcranial magnetic stimulation （rTMS） is a non-invasive treatment that can enhance the recovery of neurological function after stroke. Whether it can similarly promote the recovery of cognitive function after vascular dementia remains unknown, In this study, a rat model for vascular dementia was established by the two-vessel occlusion method. Two days after injury, 30 pulses of rTMS were ad- ministered to each cerebral hemisphere at a frequency of 0.5 Hz and a magnetic field intensity of 1,33 T. The Morris water maze test was used to evaluate learning and memory function. The Karnovsky-Roots method was performed to determine the density of cholinergic neurons in the hippocampal CA1 region. Immunohistochemical staining was used to determine the number of brain-derived neurotroph- ic factor （BDNF）-immunoreactive cells in the hippocampal CA1 region, rTMS treatment for 30 days significantly improved learning and memory function, increased acetylcholinesterase and choline acetyltransferase activity, increased the density of cholinergic neurons, and increased the number of BDNF-immunoreactive cells. These results indicate that rTMS can ameliorate learning and memory deficiencies in rats with vascular dementia, The mechanism through which this occurs might be related to the promotion of BDNF expression and subsequent restoration of cholinergic system activity in hippocampal CA 1 region.

Magnetic Stimulation Accelerating Rehabilitation of Peripheral Nerve Injury

Summary: The effect of magnetic stimulation (MS) on sciatic nerve injury was observed. After sciatic nerve was crushed in 40 Sprague Dawley (SD) rats, one randomly selected group (group D) was subjected, from the 4th day post-operatively to 3 min of continuous 70 % of maximum output of MS daily for 8 weeks. The other group (group E) served as a control group. The nerve regeneration and motor function recovery were evaluated by walking track analysis (sciatic function index, SFI; toe spreading reflex, TSR), electrophysiological, histological and acetylcholineesterase histochemistry. The SFI in the group D was greater than in the group E with the difference being statistically significant (P<0.01). TSR reached its peak on the 4th day in the group D and on the 10th day in the group E respectively. The amplitude and velocity of MCAP and NCAP in the group D was greater than in the group E with the difference being statistically significant (P<0.01), while the latency and duration of MCAP and NCAP in the group D were less than in the group E with the difference being also statistically significant (P<0.01). Histological examination showed the mean axon count above the lesion for thick myelinated fibers (>6.5 μm) in the group D was greater than in the control group with the difference being statistically significant (P<0.01), while the mean axon count below the lesion for thick myelinated fibers was less than that in the group E with the difference being statistically significant (P<0.01). The mean axon count above the lesion for thin myelinated fibers (2-6.5 μm) in the group D was greater than that in the group E with the difference being statistically significant (P<0.05), while the mean axon count below the lesion for thin myelinated in the group D was greater than that in the group E with the difference being statistically significant (P<0.01). Acetylcholine esterase examination showed that the MS could significantly increase the number of the motor neurons. There was no significant difference in the number of the motor neurons between the treatment side and the normal side (P>0.05). It can be concluded that MS can enhance functional recovery and has a considerable effect in the treatment of the peripheral nerve injury.

Analysis of the effect of repeated-pulse transcranial magnetic stimulation at the Guangming point on electroencephalograms

Here, we administered repeated-pulse transcranial magnetic stimulation to healthy people at the left Guangming （GB37） and a mock point, and calculated the sample entropy of electroencephalo- gram signals using nonlinear dynamics. Additionally, we compared electroencephalogram sample entropy of signals in response to visual stimulation before, during, and after repeated-pulse tran- scranial magnetic stimulation at the Guangming. Results showed that electroencephalogram sample entropy at left （F3） and right （FP2） frontal electrodes were significantly different depending on where the magnetic stimulation was administered. Additionally, compared with the mock point, electroencephalogram sample entropy was higher after stimulating the Guangming point. When visual stimulation at Guangming was given before repeated-pulse transcranial magnetic stimula- tion, significant differences in sample entropy were found at five electrodes （C3, Cz, C4, P3, T8） in parietal cortex, the central gyrus, and the right temporal region compared with when it was given after repeated-pulse transcranial magnetic stimulation, indicating that repeated-pulse transcranial magnetic stimulation at Guangming can affect visual function. Analysis of electroencephalogram revealed that when visual stimulation preceded repeated pulse transcranial magnetic stimulation, sample entropy values were higher at the C3, C4, and P3 electrodes and lower at the Cz and T8 electrodes than visual stimulation followed preceded repeated pulse transcranial magnetic stimula- tion. The findings indicate that repeated-pulse transcranial magnetic stimulation at the Guangming evokes different patterns of electroencephalogram signals than repeated-pulse transcranial mag- netic stimulation at other nearby points on the body surface, and that repeated-pulse transcranial magnetic stimulation at the Guangrning is associated with changes in the complexity of visually evoked electroencephalogram signals in parietal regions, central gyrus, and temporal regions.

Sphincteroplasty for fecal incontinence in the era of sacral nerve modulation

The role of sphincteroplasty in the treatment of patients with fecal incontinence due to anal sphincter defects has been questioned because the success rate declines in the long-term.A new emerging treatment for fecal incontinence,sacral nerve stimulation,has been shown to be effective in these patients.However,the success rate of sphincteroplasty may depend of several patient-related and surgical-related factors and the outcome from sphincteroplasty has been evaluated differently(with qualitative data) from that after sacral nerve stimulation(quantitative data using scoring systems and quality of life).Furthermore,the data available so far on the longterm success rate after sacral nerve modulation do not differ substantially from those after sphincteroplasty.The actual data do not support the replacement of sphincteroplasty with sacral nerve stimulation in patients with fecal incontinence secondary to sphincter defects.

Does a combined intervention program of repetitive transcranial magnetic stimulation and intensive occupational therapy affect cognitive function in patients with post-stroke upper limb hemiparesis?

Low-frequency repetitive transcranial magnetic stimulation（LF-r TMS） to the contralesional hemisphere and intensive occupational therapy（i OT） have been shown to contribute to a significant improvement in upper limb hemiparesis in patients with chronic stroke. However, the effect of the combined intervention program of LF-r TMS and i OT on cognitive function is unknown. We retrospectively investigated whether the combined treatment influence patient＇s Trail-Making Test part B（TMT-B） performance, which is a group of easy and inexpensive neuropsychological tests that evaluate several cognitive functions. Twenty-five patients received 11 sessions of LF-r TMS to the contralesional hemisphere and 2 sessions of i OT per day over 15 successive days. Patients with right- and left-sided hemiparesis demonstrated significant improvements in upper limb motor function following the combined intervention program. Only patients with right-sided hemiparesis exhibited improved TMT-B performance following the combined intervention program, and there was a significant negative correlation between Fugl-Meyer Assessment scale total score change and TMT-B performance. The results indicate the possibility that LF-r TMS to the contralesional hemisphere combined with i OT improves the upper limb motor function and cognitive function of patients with right-sided hemiparesis. However, further studies are necessary to elucidate the mechanism of improved cognitive function.

Right lower limb apraxia in a patient with left supplementary motor area infarction: intactness of the corticospinal tract confirmed by transcranial magnetic stimulation

We reported a 50-year-old female patient with left supplementary motor area infarction who presented right lower limb apraxia and investigated the possible causes using transcranial magnetic stimulation. The patient was able to walk and climb stairs spontaneously without any assistance at 3 weeks after onset. However, she was unable to intentionally move her right lower limb although she understood what she supposed to do. The motor evoked potential evoked by transcranial magnetic stimulation from the right lower limb was within the normal range, indicating that the corticospinal tract innervating the right lower limb was uninjured. Thus, we thought that her motor dysfunction was not induced by motor weakness, and confirmed her symptoms as aprax- ia. In addition, these results also suggest that transcranial magnetic stimulation is helpful for diagnosing apraxia.

Impulse magnetic stimulation facilitates synaptic regeneration in rats following sciatic nerve injury

The current studies describing magnetic stimulation for treatment of nervous system diseases mainly focus on transcranial magnetic stimulation and rarely focus on spinal cord magnetic stimulation. Spinal cord magnetic stimulation has been confirmed to promote neural plasticity after injuries of spinal cord, brain and peripheral nerve. To evaluate the effects of impulse magnetic stimulation of the spinal cord on peripheral nerve regneration, we compressed a 3 mm segment located in the middle third of the hip using a sterilized artery forceps to induce ischemia. Then, all animals underwent impulse magnetic stimulation of the lumbar portion of spinal crod and spinal nerve roots daily for 1 month. Electron microscopy results showed that in and below the injuryed segment, the inflammation and demyelination of neural tissue were alleviated, apoptotic cells were reduced, and injured Schwann cells and myelin fibers were repaired. These findings suggest that high-frequency impulse magnetic stimulation of spinal cord and corresponding spinal nerve roots promotes synaptic regeneration following sciatic nerve injury.

Prolonged electrical stimulation causes no damage to sacral nerve roots in rabbits

Previous studies have shown that, anode block electrical stimulation of the sacral nerve root can produce physiological urination and reconstruct urinary bladder function in rabbits. However, whether long-term anode block electrical stimulation causes damage to the sacral nerve root re- mains unclear, and needs further investigation. In this study, a complete spinal cord injury model was established in New Zealand white rabbits through T9_10 segment transection. Rabbits were given continuous electrical stimulation for a short period and then chronic stimulation for a longer period. Results showed that compared with normal rabbits, the structure of nerve cells in the anterior sacral nerve roots was unchanged in spinal cord injury rabbits after electrical stimu- lation. There was no significant difference in the expression of apoptosis-related proteins such as Bax, Caspase-3, and Bcl-2. Experimental findings indicate that neurons in the rabbit sacral nerve roots tolerate electrical stimulation, even after long-term anode block electrical stimulation.

Adverse events of sacral neuromodulation for fecal incontinence reported to the federal drug administration

AIM:To investigate the nature and severity of AE related to sacral neurostimulation(SNS).METHODS:Based on Pubmed and Embase searches,we identified published trials and case series of SNS for fecal incontinence(FI)and extracted data on adverse events,requiring an active intervention.Those problems were operationally defined as infection,device removal explant or need for lead and/or generator replacement.In addition,we analyzed the Manufacturer and User Device Experience registry of the Federal Drug Administration for the months of August-October of2015.Events were included if the report specifically mentioned gastrointestinal(GI),bowel and FI as indication and if the narrative did not focus on bladder symptoms.The classification,reporter,the date of the recorded complaint,time between initial implant and report,the type of AE,steps taken and outcome were extracted from the report.In cases of device removal or replacement,we looked for confirmatory comments by healthcare providers or the manufacturer.RESULTS:Published studies reported adverse events and reoperation rates for 1954 patients,followed for 27(1-117)mo.Reoperation rates were 18.6%(14.2-23.9)with device explants accounting for 10.0%(7.8-12.7)of secondary surgeries;rates of device replacement or explant or pocket site and electrode revisions increased with longer follow up.During the period examined,the FDA received 1684 reports of AE related to SNS with FI or GI listed as indication.A total of 652 reports met the inclusion criteria,with 52.7%specifically listing FI.Lack or loss of benefit(48.9%),pain or dysesthesia(27.8%)and complication at the generator implantation site(8.7%)were most commonly listed.Complaints led to secondary surgeries in 29.7%of the AE.Reoperations were performed to explant(38.2%)or replace(46.5%)the device or a lead,or revise the generator pocket(14.6%).Conservative management changes mostly involved changes in stimulation parameters(44.5%),which successfully addressed concerns in 35.2%of cases that included information about treatment results.CONCLUSION:With reoperation rates around 20%,physicians need to fully disclose the high likelihood ofcomplications and secondary interventions and exhaust non-invasive treatments,including transcutaneous stimulation paradigms.

Nerve root magnetic stimulation improves locomotor function following spinal cord injury with electrophysiological improvements and cortical synaptic reconstruction

Following a spinal cord injury,there are usually a number of neural pathways that remain intact in the spinal cord.These residual nerve fibers are important,as they could be used to reconstruct the neural circuits that enable motor function.Our group previously designed a novel magnetic stimulation protocol,targeting the motor cortex and the spinal nerve roots,that led to significant improvements in locomotor function in patients with a chronic incomplete spinal cord injury.Here,we investigated how nerve root magnetic stimulation contributes to improved locomotor function using a rat model of spinal cord injury.Rats underwent surgery to clamp the spinal cord at T10;three days later,the rats were treated with repetitive magnetic stimulation(5 Hz,25 pulses/train,20 pulse trains)targeting the nerve roots at the L5-L6 vertebrae.The treatment was repeated five times a week over a period of three weeks.We found that the nerve root magnetic stimulation improved the locomotor function and enhanced nerve conduction in the injured spinal cord.In addition,the nerve root magnetic stimulation promoted the recovery of synaptic ultrastructure in the sensorimotor cortex.Overall,the results suggest that nerve root magnetic stimulation may be an effective,noninvasive method for mobilizing the residual spinal cord pathways to promote the recovery of locomotor function.

Non-invasive transcutaneous electrical stimulation in the treatment of overactive bladder

We reviewed the literature on transcutaneous electrical nerve stimulation(TENS)used as a therapy for overactive bladder(OAB)symptoms,with a particular focus on:stimulation site,stimuli parameters,neural structures thought to be targeted,and the clinical and urodynamic outcomes achieved.The majority of studies used sacral or tibial nerve stimulation.The literature suggests that,whilst TENS therapy may have neuromodulation effects,patient are unlikely to benefit to a significant extent from a single application of TENS and indeed clear benefits from acute studies have not been reported.In long-term studies there were differences in the descriptions of stimulation intensity,strategy of the therapy,and positioning of the electrodes,as well as in the various symptoms and pathology of the patients.Additionally,most studies were uncontrolled and hence did not evaluate the placebo effect.Little is known about the underlying mechanism by which these therapies work and therefore exactly which structures need to be stimulated,and with what parameters.There is promising evidence for the efficacy of a transcutaneous stimulation approach,but adequate standardisation of stimulation criteria and outcome measures will be necessary to define the best way to administer this therapy and document its efficacy.

Low frequency repetitive transcranial magnetic stimulation improves motor dysfunction after cerebral infarction

Low frequency （≤ 1 Hz） repetitive transcranial magnetic stimulation （rTMS） can affect the excitability of the cerebral cortex and synaptic plasticity. Although this is a common method for clinical treatment of cerebral infarction, whether it promotes the recovery of motor function remains controversial. Twenty patients with cerebral infarction combined with hemiparalysis were equally and randomly divided into a low frequency rTMS group and a control group. The patients in the low frequency rTMS group were given 1-Hz rTMS to the contralateral primary motor cortex with a stimulus intensity of 90% motor threshold, 30 minutes/day. The patients in the control group were given sham stimulation. After 14 days of treatment, clinical function scores （National Institute of Health Stroke Scale, Barthel Index, and Fugl-Meyer Assessment） improved significantly in the low frequency rTMS group, and the effects were better than that in the control group. We conclude that low frequency （1 Hz） rTMS for 14 days can help improve motor function after cerebral infarction.

Effect of Paired Associative Stimulation on Motor Cortex Excitability in Rats

Paired associative stimulation (PAS),combining transcranial magnetic stimulation (TMS) with electrical peripheral nerve stimulation (PNS) in pairs with an optimal interstimulus interval (ISI)in between,has been shown to influence the excitability of the motor cortex (MC)in humans.However,the underlying mechanisms remain unclear.This study was designed to explore an optimal protocol of PAS,which can modulate the excitability of MC in rats,and to investigate the underlying mechanisms. The resting motor thresholds (RMTs) of TMS-elicited motor evoked potentials (MEPs) recorded from the gastrocnemius muscle and the latency of P1 component of somatosensory evoked potentials (SEPs) induced by electrical tibial nerve stimulation were determined in male Sprague-Dawley rats (n=10).Sixty rats were then randomly divided into 3 groups:a PAS group (further divided into 10 subgroups at various ISIs calculated by using the latency of P1,n=5,respectively),a TMS (only)group (n=5)and a PNS (only)group (n=5).Ninety repetitions of PAS,TMS and PNS were administered to the rats in the 3 groups,respectively,at the frequency of 0.05 Hz and the intensity of TMS at 120% RMT and that of PNS at 6 mA.RMTs and motor evoked potentials'amplitude (MEPamp)were recorded before and immediately after the interventions.It was found that the MEPamp significantly decreased after PAS at ISI of 5 ms (P<0.05),while the MEPamp significantly increased after PAS at ISI of 15ms,as compared with those before the intervention (P<0.05).However,the RMT did not change significantly after PAS at ISI of 5 ms or 15 ms (P>0.05).PAS at other ISis as well as the sole use of TMS and PNS induced no remarkable changes in MEPamp and RMT.In conclusion,PAS can influence motor cortex excitability in rats.Neither TMS alone nor PNS alone shows significant effect.

High-frequency magnetic stimulation attenuates beta-amyloid protein 1-42 neurotoxicity in organotypic hippocampal slices

Repetitive transcranial magnetic stimulation （rTMS） has been utilized as a therapeutic tool for neurodegenerative disorders including Alzheimer＇s disease. However, the precise mechanisms of its clinical effects remain unknown. β-amyloid （Aβ） exhibits direct neurotoxic effects and is closely related to neuronal degeneration in Alzheimer＇s disease. Therefore, it has been hypothesized that the neuroprotective effects of rTMS are related to the mechanisms of protection against Aβ neurotoxicity. Organotypic hippocampal slices were prepared from 8-day old, Sprague Dawley rats. The tissue slices were exposed to 100 μmol/L Al3142 since day 12 in vitro with and without high-frequency （20 Hz） magnetic stimulation. Magnetic stimulation efficacy was evaluated by measuring neuronal nuclei （NeuN） protein expression and by observing cultures following propidium iodide fluorescence staining and bromodeoxyuridine （BrdU） immunohistochemistry. Lactate dehydrogenase activity was detected in the culture media to evaluate hippocampal neuronal damage. Our results demonstrated that high-frequency magnetic stimulation significantly reversed the reduction of NeuN protein expression because of Aβ1-42 exposure （P 〈 0.05） and significantly reduced the number of damaged cells in the hippocampal slices （P 〈 0.05）. However, lactate dehydrogenase levels and anti-BrdU staining results did not reveal any statistical differences These findings indicate that high-frequency magnetic stimulation might have protective effect on hippocampal neurons from Aβ1-42 neurotoxicity.