Effects Of Low-frequency Electrical Stimulation Research Articles

Effect of Low-Frequency Electrical Stimulation Combined with Abdominal Acupoint Massage on Postoperative Gastrointestinal Function Recovery after Cesarean Section: A Prospective Randomized Study

Background: This study aimed to investigate the effects of low-frequency electrical stimulation combined with abdominal acupoint massage on the recovery of gastrointestinal function following cesarean section. Methods: A total of 60 postoperative patients were randomly assigned to either the control group (group A, n = 30) or the observation group (group B, n = 30) between January 2021 to December 2021. The control group received conventional interventions, while the observation group received a nursing intervention consisting of low-frequency electrical stimulation combined with abdominal acupoint massage starting at 10–12 hours after the operation. The primary outcomes included the time to first bowel sound, time to flatus, time to defecation, and time to lactation. The secondary outcomes included postoperative visual analogue scale (VAS) pain scores, the rate and severity of abdominal distension, and serum levels of prolactin (PRL) and vasoactive intestinal peptide (VIP). Results: The observation group had significantly earlier restoration of bowel sounds, passage of first flatus, and first defecation than the control group (p < 0.001). The VAS scores in the observation group were significantly lower than those in the control group at 24 h, 48 h, and 72 h after the operation (p < 0.001). The incidence of abdominal distension in the observation group (13.3%, 4/30) was lower than that in the control group (36.7%, 11/30) (p < 0.05). Furthermore, compared to the control group, the observation group showed a significant increase in serum PRL levels and a significant decrease in VIP levels after treatment (p < 0.001). Conclusions: The application of low-frequency electrical stimulation combined with abdominal acupoint massage after cesarean section can expedite the recovery of gastrointestinal function and reduce pain and complications, such as abdominal distension. This approach can be used in clinical practice to accelerate the recovery of intestinal function after cesarean section. Clinical Trial Registration: The study was registered with the ISRCTN registry (https://www.isrctn.com/), registration number: ISRCTN16533743.

Is Electrical Stimulation Useful for Patients with Duchenne Muscular Dystrophy? A Mini-review

Duchenne muscular dystrophy (DMD) is a hereditary progressive neuromuscular disease of childhood. The survival rate of DMD patients is extremely low. In physiotherapy, electrical stimulation is frequently applied to rehabilitate these patients. The present study aimed to evaluate the effects of electrical stimulation on the muscles of patients with DMD. In this regard limited relevant studies were found, some of which reported the positive effects of low-frequency electrical stimulation on improving muscle strength. Conversely, there were reports of the detrimental effects of electrical stimulation on muscle fibers. Overall, there is no standard guideline for electrical stimulation in patients with DMD, and further research is required with adequate sample size and follow-up.

Effect of Low-Frequency Electrical Stimulation Combined with Tonifying Kidney and Blood Pills on Uterine Rejuvenation after Abortion.

Objective This study aimed to observe the clinical efficacy of low-frequency electrical stimulation therapy combined with tonifying the kidney and activating blood pills to promote uterine recovery after abortion and its effect on heat-shock protein (HSP)70 and HSP90. Methods All cases were women with early pregnancy who underwent an abortion at the Third Affiliated Hospital of Nanchang University from September 2019 to September 2020. They were divided into two groups in accordance with the principle of patient voluntariness: 237 cases in the experimental group and 143 cases in the control group. Patients in both groups were given low-frequency electrical stimulation after surgery. In addition, patients in the experimental group began to take the Dingkun pill orally (one pill per time, two times per day) from the first day of surgery and continued to take it until their menstruation returned to normal. Abdominal pain, the duration of vaginal bleeding, and the amount of bleeding were observed in both groups. Uterine size, endometrial thickness, and urinary human chorionic gonadotropin (HCG) status were also observed at 2 weeks postoperatively to determine preoperative and postoperative HSP70 and HSP90 serum levels. The time of menstrual resumption, menstrual period, and menstrual volume were observed and compared with preoperative menstruation. The occurrence of complications, such as a residual uterine cavity, uterine effusion, menstrual irregularities, and reproductive tract infections, during the follow-up period was also recorded in both groups. Results Comparison of the endometrial thickness (mm) and uterine size (sum of the three diameters) on uterine adnexal ultrasound at 2-week postoperative review was better in the experimental group than in the control group (p < 0.05). No statistically significant difference was found between the two groups in terms of residual uterine cavity and blood accumulation in the uterine cavity and the results of the urine pregnancy test (p > 0.05). Serum HSP70 and HSP90 levels were significantly higher in the control group than in the experimental group 2 weeks after surgery (p < 0.05). Postoperative HSP70 and HSP90 levels were significantly higher than preoperative levels in both groups (p < 0.05). The degree of postoperative abdominal pain in the experimental group was less severe than that in the control group, and the duration was shorter (p < 0.05). No statistically significant differences were observed when comparing the duration of postoperative vaginal bleeding and the amount of bleeding (p > 0.05). The time of the first menstrual resumption and menstrual volume were more satisfactory in the experimental group than in the control group (p < 0.05). No adverse reactions occurred in either group of patients receiving treatment. ConclusionLow-frequency electrical stimulation combined with tonifying the kidney and invigorating blood pills could effectively promote uterine rejuvenation after abortion, conducive to improving patients' postoperative abdominal pain, promoting menstrual recovery and maintaining menstrual flow.

Low-frequency electrical stimulation alleviates immobilization-evoked disuse muscle atrophy by repressing autophagy in skeletal muscle of rabbits

BackgroundThe study aimed to investigate the effect of low-frequency electrical stimulation (LFES) on disuse muscle atrophy and its mechanism in a rabbit model of knee extension contracture.MethodsThis study involved two experiments. In the time-point experiment, 24 rabbits were randomly divided into 4 groups: Control 1 (Ctrl1 group), immobilization for 2 weeks (I-2 group), immobilization for 4 weeks (I-4 group), and immobilization for 6 weeks (I-6 group). In the intervention experiment, 24 rabbits were randomly divided into 4 groups: Control 2 (Ctrl2 group), electrical stimulation (ESG group), natural recovery (NRG group), and electrical stimulation treatment (ESTG group). All intervention effects were assessed by evaluating the knee joint range of motion (ROM), cross-sectional area (CSA) of the rectus femoris muscle, and expression of autophagy-related proteins.ResultsThe time-point experiment showed that immobilization reduced the knee ROM, reduced the rectus femoris muscle CSA, and activated autophagy in skeletal muscle. The levels of five autophagy-related proteins [mammalian target of rapamycin (mTOR), phosphorylated mTOR (p-mTOR), autophagy-related protein 7 (Atg7), p62, and microtubule-associated protein light chain 3B-II (LC3B-II)] were significantly elevated in the skeletal muscle of the I-4 group. The intervention experiment further showed that LFES significantly improved the immobilization-induced reductions in ROM and CSA. Additionally, LFES resulted in a significant decrease in the protein expression of mTOR, p-mTOR, Atg7, p62, and LC3B-II in the rectus femoris muscle.ConclusionsLFES alleviates immobilization-evoked disuse muscle atrophy possibly by inhibiting autophagy in the skeletal muscle of rabbits.

Low-Frequency Electrical Stimulation Promotes Satellite Cell Activities to Facilitate Muscle Regeneration at an Early Phase in a Rat Model of Muscle Strain.

The capability of regeneration for skeletal muscle after injury depends on the differentiation and proliferation ability of the resident stem cells called satellite cells. It has been reported that electrical stimulation was widely used in clinical conditions to facilitate muscle regeneration after injury, but the characterization of satellite cell responses to the context of low-frequency electrical stimulation in early-phase muscle strain conditions has not been fully clarified. In this study, we aim to investigate the effects of low-frequency electrical stimulation (frequency: 20 Hz; duration: 30 minutes, twice daily) on satellite cell activities in a rat model for the early phase of muscle strain. Firstly, we adopted our previously developed rat model to mimic the early phase of muscle strain in human. After then, we examined the effects of low-frequency electrical stimulation on histopathological changes of the muscle fiber by hematoxylin and eosin (H&E) staining. Finally, we investigated the effects of low-frequency electrical stimulation on satellite cell proliferation and differentiation by quantification of the expression level of the specific proteins using western blot analyses. The muscle strain in biceps femoris muscles of rats can be induced by high-speed rotation from knee flexion 50° to full knee extension at 960°·s−1 angular velocity during its tetany by activating the sciatic nerve, as evidenced by a widening of the interstitial space between fibers, and more edema or necrosis fibers were detected in the model rats without treatment than in control rats. After treatment with low-frequency electrical stimulation (frequency: 20 Hz; duration: 30 minutes, twice daily), the acute strained biceps femoris muscles of rats showed obvious improvement of histomorphology as indicated by more mature muscle fibers with well-ordered formation with clear boundaries. Consistently, the expression levels of the MyoD and myogenin were marked higher than those in the rats in the animal model group, indicating increased satellite cell proliferating and differentiating activities by low-frequency electrical stimulation. This study shows that low-frequency electrical stimulation provides an effective stimulus to upregulate the protein expression of MyoD/myogenin and accelerate the restoration of structure during the early phase of muscle strain. This may have significance for clinical practice. Optimization of low-frequency electrical stimulation parameters may enhance the therapeutic outcome in patients.

Histological evaluation of the effect of low-frequency electric stimulation on healing Achilles tendons in rats.

ABSTRACTPurpose:Histologically evaluate the effects of low frequency electrical stimulation in the treatment of Achilles tendon injuries in rats.Methods:Thirty-four rats underwent Achilles tendon tenotomy and tenorrhaphy. They were randomly allocated in two groups. Half of the sample constituted the experiment group, whose lesions were stimulated with 2 Hz, nonpolarized current and 1 mA, for 14 days. The other animals formed the control group. They were evaluated at 2, 4 and 6 weeks. The histological study was carried out, the collagen density and the wound maturity index were measured.Results:The healing score was higher in the group stimulated at the 6th week (p = 0.018). The density collagen 1 was higher in the group treated at the three times (p = 0.004) and that collagen 3 was higher in the group treated at 6 weeks (p = 0.004). Together, collagen 1 and 3 were higher in the group stimulated at 4 and 6 weeks (p = 0.009, p = 0.004). The maturity index was higher in this group at the three moments (p = 0.017 p = 0.004 and p = 0.009).Conclusion:Low frequency electric stimulation improved healing and increased the quantity of collagen.

Presynaptic GABAB receptors underlie the antiepileptic effect of low-frequency electrical stimulation in the 4-aminopyridine model of epilepsy in brain slices of young rats

Low-frequency electrical stimulation (LFES) of the brain is one of the promising methods for helping patients with pharmacoresistant epilepsy. However, the mechanism of the antiepileptic effect of LFES is still unclear. We applied electrophysiological and pharmacological tools and mathematical modeling to investigate it. Using the 4-aminopyridine (4-AP) model of epileptiform activity in juvenile rat brain slices, we found that LFES increased the interval between ictal discharges (IDs) in the entorhinal cortex. The blockade of GABAA, GABAB, AMPA, or NMDA synaptic receptors strongly affected the characteristics of epileptiform discharges in slices. However, only under the blockade of GABAB receptors, LFES becomes entirely ineffective, indicating that the activation of GABAB receptors underlies the main LFES antiepileptic effect. Further experiments allowed us to suggest that LFES activates mostly presynaptic GABAB receptors, which decrease the probability of glutamate release. In line with this hypothesis is the following data: 1) LFES reduces the short-term synaptic depression of excitatory postsynaptic currents similar to the agonist of GABAB receptors SKF-97541; 2) the blockade of excitatory amino acid transporters diminishes the antiepileptic effect of LFES; 3) modeling of the effects of LFES on the probability of glutamate release with a previously proposed mathematical model of epileptiform activity Epileptor-2 also shows the increase of the interval between IDs. Our findings point out a crucial role of presynaptic GABAB receptors in the antiepileptic effect of LFES in the 4-AP model in juvenile rat brain slices.

The Effect of Low-Frequency Electrical Stimulation on Denervation Atrophy in Man

The effect of low frequency electrical stimulation (LES) on denervation atrophy and recovery of the muscles was examined in a group of 73 patients with a single or a combined total lesion of the median, ulnar or peroneal nerves. The differences between the patients were evaluated by means of clinical muscle force testing, EMG, dynamometry (ulnar and median nerve lesions), computer tomography (ulnar nerve lesions) and ultrasonography (median and peroneal nerve lesions). A beneficial effect of LES could not be shown.

Tensiometric evaluation of the effect of lowfrequency electric stimulation on healing Achilles tendons in rats.

Purpose:To evaluate the effects of low-frequency electric stimulation on biomechanics following surgical treatment of the Achilles tendon in rats.Methods:Forty-two rats were divided into two groups. One was given electric stimulation and the other was not. All were submitted to Achilles tenotomy and tenorrhaphy performed with a modified Kessler stitch. The experiment group underwent electric stimulation with 2 Hz, a nonpolarized current of 1 mA intensity for 14 days. The animals were euthanized at 2, 4 and 6 weeks for the biomechanical study.Results:The work performed, that is, the tendon’s capacity to absorb energy until rupture, was greater in the electrically stimulated group in the 2nd (p = 0.032) and in the 6th week (p = 0.010). The maximum tension, which is the capacity to support a load, was higher in the treated group in the 2nd (p = 0.030) and the 6th week (p = 024). These results indicate greater resistance of the electrically stimulated tendons. An analysis of the elastic module showed no differences.Conclusion:Low-frequency electric stimulation increased the resistance of the tendons at 2 and 6 weeks of evolution in rats.

Low-frequency Stimulation Decreases Hyperexcitability Through Adenosine A1 Receptors in the Hippocampus of Kindled Rats.

Introduction:In this study, the role of A1 adenosine receptors in improving the effect of Low-Frequency Electrical Stimulation (LFS) on seizure-induced hyperexcitability of hippocampal CA1 pyramidal neurons was investigated.Methods:A semi-rapid hippocampal kindling model was used to induce seizures in male Wistar rats. Examination of the electrophysiological properties of CA1 pyramidal neurons of the hippocampus using whole-cell patch-clamp recording 48 h after the last kindling stimulation revealed that the application of LFS as two packages of stimulations at a time interval of 6 h for two consecutive days could significantly restore the excitability CA1 pyramidal neurons evidenced by a decreased in the of the number of evoked action potentials and enhancement of amplitude, maximum rise slope and decay slope of the first evoked action potential, rheobase, utilization time, adaptation index, first-spike latency, and post-AHP amplitude. Selective locked of A1 receptors by the administration of 8-Cyclopentyl-1,3-dimethylxanthine (1 μM, 1 μl, i.c.v.) before applying each LFS package, significantly reduced LFS effectiveness in recovering these parameters.Results:On the other hand, selective activation of A1 receptors by an injection of N6-cyclohexyladenosine (10 μM, 1 μl, i.c.v.), instead of LFS application, could imitate LFS function in improving these parameters.Conclusion:It is suggested that LFS exerts its efficacy on reducing the neuronal excitability, partially by activating the adenosine system and activating its A1 receptors.

Modest Effects of Low-frequency Electrical Stimulation on Patients with Chronic Insomnia in an Open Trial

Modest Effects of Low-frequency Electrical Stimulation on Patients with Chronic Insomnia in an Open Trial

Cellular Changes in Injured Rat Spinal Cord Following Electrical Brainstem Stimulation.

Spinal cord injury (SCI) is a major cause of disability and pain, but little progress has been made in its clinical management. Low-frequency electrical stimulation (LFS) of various anti-nociceptive targets improves outcomes after SCI, including motor recovery and mechanical allodynia. However, the mechanisms of these beneficial effects are incompletely delineated and probably multiple. Our aim was to explore near-term effects of LFS in the hindbrain’s nucleus raphe magnus (NRM) on cellular proliferation in a rat SCI model. Starting 24 h after incomplete contusional SCI at C5, intermittent LFS at 8 Hz was delivered wirelessly to NRM. Controls were given inactive stimulators. At 48 h, 5-bromodeoxyuridine (BrdU) was administered and, at 72 h, spinal cords were extracted and immunostained for various immune and neuroglial progenitor markers and BrdU at the level of the lesion and proximally and distally. LFS altered cell marker counts predominantly at the dorsal injury site. BrdU cell counts were decreased. Individually and in combination with BrdU, there were reductions in CD68 (monocytes) and Sox2 (immature neural precursors) and increases in Blbp (radial glia) expression. CD68-positive cells showed increased co-staining with iNOS. No differences in the expression of GFAP (glia) and NG2 (oligodendrocytes) or in GFAP cell morphology were found. In conclusion, our work shows that LFS of NRM in subacute SCI influences the proliferation of cell types implicated in inflammation and repair, thus providing mechanistic insight into deep brain stimulation as a neuromodulatory treatment for this devastating pathology.

Endocannabinoid CB1 receptors are involved in antiepileptogenic effect of low frequency electrical stimulation during perforant path kindling in rats

IntroductionAdministration of low-frequency electrical stimulation (LFS) at the kindling site has an antiepileptogenic effect. In the present study, we investigated the role of cannabinoid receptors type 1 (CB1) in mediating the inhibitory effects of LFS on the development of perforant path kindled seizures. MethodsFor seizure generation, rats were kindled by electrical stimulation of perforant path in semi-rapid kindling manner (12 stimulations per day at 10 min intervals at afterdischarge threshold intensity).To determine the effect of LFS (0.1 ms pulse duration at 1 Hz, 800 pulses) on seizure generation, LFS was applied to the perforant path 5 min after the last kindling stimulation daily. AM281, a CB1 receptor antagonist, was microinjected into the lateral ventricle immediately after the last kindling stimulation (before LFS application) at the doses of 0.5 and 2 μg/μl during kindling procedure. The expression of cannabinoid receptors in the dentate gyrus was also investigated using immunohistochemistry. ResultsApplication of LFS had inhibitory effect on development of kindled seizures (kindling rate). Microinjection of AM281 (0.5 μg/μl) immediately after the last kindling stimulation (before LFS application) reduced the inhibitory effect of LFS on the kindling rate and suppressed the effects of LFS on potentiation (increasing the magnitude) of both population spike amplitude and population excitatory postsynaptic potential slope during kindling acquisition. AM281 pretreatment also prevented the effects of LFS on kindling-induced increase in early and late paired pulse depression. The higher dose of AM281 (2 μg/μl) failed to exert the effects observed with its lower dose (0.5 μg/μl). In addition, there was a decreased CB1 receptors immunostaining in kindled animals compared to control. However, application of LFS following kindling stimulations led to overexpression of CB1 receptors in the dentate gyrus. ConclusionObtained results showed that activation of overexpressed cannabinoid CB1 receptors by endogenous cannabinoids may have a role in mediating the inhibitory effect of LFS on perforant path kindled seizures.

ERK activation is required for the antiepileptogenic effect of low frequency electrical stimulation in kindled rats

IntroductionThe signaling pathways involved in the antiepileptogenic effect of low frequency electrical stimulation (LFS) have not been fully understood. In the present study the role of extracellular signal-regulated kinase (ERK) signaling cascade was investigated in mediating the inhibitory effects of LFS on kindled seizures. MethodsAnimals received kindling stimulations for seven days (the mean number of stimulation days for achieving stage 5 seizure) according to semi-rapid perforant path kindling protocol (12 stimulations per day at 10 min intervals). LFS (0.1 ms pulse duration at 1 Hz, 800 pulses) was applied at 5 min after the last kindling stimulation every day. During the kindling procedure, FR180204 (inhibitor of ERK) was daily microinjected (1 μg/μl; intracerebroventricular) immediately after the last kindling stimulation and before LFS application. The expression of activated ERK (p-ERK) in the dentate gyrus was also investigated using immunohistochemistry technique. ResultsApplication of LFS at 5 min after the last kindling stimulation had inhibitory effect on kindling rate. FR180204 had no significant effect on seizure parameters when administered at the dose of 1 μg/μl in kindled group of animals. However, microinjection of FR180204 before LFS application reduced the inhibitory effect of LFS on seizure severity and field potential parameters (i.e. the slope of population field excitatory postsynaptic potentials and population spike amplitude) during kindling. FR180204 also blocked the preventing effects of LFS on kindling-induced increase in early (at 10–40 ms intervals) and late (at 300–1000 ms intervals) paired pulse depression. In addition, application of LFS following kindling stimulations increased the expression of p-ERK in the dentate gyrus. ConclusionObtained results showed ERK signaling pathway had important role in mediating the antiepileptogenic effect of LFS in perforant path kindling. These findings represent a promising opportunity to gain insight about LFS mechanism in epilepsy therapy.

Effect of Low-Frequency Electrical Stimulation on the High-K+-Induced Neuronal Hyperexcitability in Rat Hippocampal Slices

Low-frequency electrical stimulation (LFS) is a potential therapeutic method for epilepsy treatment. However, the effect of different LFS characteristics including the number of pulses, intensity and the time of application on its antiepileptic action has not been completely determined. In the present study, epileptiform activity (EA) was induced in hippocampal slices by high-K+ solution which was washed out after 20 min. The changes in the electrophysiological properties of CA1 pyramidal neurons were measured during and 30 min after EA using whole-cell patch-clamp recording. EA occurrence resulted in neuronal hyperexcitability. Application of 1-Hz LFS to the Schaffer collaterals at 600 and 900 pulses and two intensities (equal and 1.5 times more than an intensity sufficient to elicits a 5-mV EPSP) at the beginning of EA showed that 900-pulse LFS at high intensity had stronger preventing effect on high-K+-induced neuronal hyperexcitability by increasing the rheobase current, utilization time, first-spike latency, delay to first-rebound action potential and decreasing the number of rebound action potential. In addition, application of high-intensity 900-pulse LFS had better inhibitory effect on the neuronal hyperexcitability when applied at the beginning of EA compared to its administration before or at 8–10 min after EA. Therefore, it may suggest the inhibitory action of LFS on the neuronal hyperexcitability is augmented by increasing its number of pulses and intensity. In addition, there is a time window for LFS application so that its application at the beginning of EA has better inhibitory effect.

The effect of low-frequency electrical stimulation at acupoints on the plasma DA of stroke survivors with insomnia: A clinical trial

Objective To compare the therapeutic effect of low-frequency electrical stimulation at the acupoints with that of conventional Western medication among patients with post-stroke insomnia, and explore the underlying mechanism. Methods Totally 120 stroke survivors with insomnia were randomly divided into an intervention group, a medication group and a placebo group, each of 40. The intervention group received low-frequency electrical stimulation at the Dazhui and Shenshu acupoints once a day for 30 consecutive days. The medication group received 1mg estazolam capsules and the placebo group took 1mg starch capsules. The average levels of plasma dopamine (DA) of the 3 groups were compared before and after the intervention and therapeutic efficacy was estimated. Results After the intervention, the total effective rate of the intervention group was 95% (38/40). For the medication group it was 92.5% (37/40) and for the placebo group it was 17.9% (7/39). The former two treatments were significantly more effective than no treatment (the placebo). There was no significant change in the average level of plasma DA before and after the treatment in the placebo group, but significant improvement was observed in the other two groups. There was no significant difference in plasma DA between the two treatment groups after the treatment. Conclusion Low-frequency electrical stimulation at acupoints is safe and equally as effective as estazolam for treating post-stroke insomnia. Both may alleviate post-stroke insomnia by increasing plasma DA levels. Key words: Insomnia; Low-frequency electric stimulation; Acupoints; Dopamine; Randomized controlled trials

Effects of low-frequency electrical stimulation of the anterior piriform cortex on kainate-induced seizures in rats.

Recent evidence in animals and humans suggests that low-frequency stimulation (LFS) has significant antiepileptic properties. The anterior piriform cortex (APC) is a highly susceptible seizure-trigger zone and may be critical for the initiation and propagation of seizures originating from cortical and limbic foci. We used the kainic acid (KA) seizure model in rats to assess the therapeutic effect of LFS of the APC on seizures. Adult male Sprague-Dawley rats were implanted with electrodes in the left APC and recording electrodes bilaterally in the hippocampal CA3 regions. Rats were monitored continuously with video-EEG after the emergence of spontaneous recurrent seizures that followed induction of status epilepticus by intraperitoneal KA. After two weeks of baseline recordings to determine seizure frequency, LFS of the APC was applied 60-min On 15-min Off, for two weeks with 1Hz biphasic square waves, 0.2ms pulse width, at 200μA. Another 2-week period of video-EEG monitoring was done after the cessation of LFS to study the carry-over effect. Changes in seizure frequency, severity, and duration between baseline, during LFS, and post-LFS were analyzed using the Poisson regression model. Overall seizure frequency decreased during the post-LFS period to 5% of that at baseline (p=0.003). Severe seizures (stages 4 and 5 on the Racine scale) decreased to 0% of the baseline during the post-LFS period. Two weeks of LFS of the APC reduced spontaneous seizure frequency and severity in the KA model with the effect outlasting the stimulation. Our findings suggest that the APC can be an important therapeutic target for stimulation in epilepsy.

Effect of low frequency electrical stimulation on seizure-induced short- and long-term impairments in learning and memory in rats

Kindled seizures can impair learning and memory. In the present study the effect of low-frequency electrical stimulation (LFS) on kindled seizure-induced impairment in spatial learning and memory was investigated and followed up to one month. Animals were kindled by electrical stimulation of hippocampal CA1 area in a semi-rapid manner (12 stimulations per day). One group of animals received four trials of LFS at 30s, 6h, 24h, and 30h following the last kindling stimulation. Each LFS trial was consisted of 4 packages at 5min intervals. Each package contained 200 monophasic square wave pulses of 0.1ms duration at 1Hz. The Open field, Morris water maze, and novel object recognition tests were done 48h, 1week, 2weeks, and one month after the last kindling stimulation respectively. Kindled animals showed a significant impairment in learning and memory compared to control rats. LFS decreased the kindling-induced learning and memory impairments at 24h and one week following its application, but not at 2week or 1month after kindling. In the group of animals that received the same 4 trials of LFS again one week following the last kindling stimulation, the improving effect of LFS was observed even after one month. Obtained results showed that application of LFS in fully kindled animals has a long-term improving effect on spatial learning and memory. This effect can remain for a long duration (one month in this study) by increasing the number of applied LFS.

Study of the anti-seizure effects of low-frequency stimulation following kindling (a review of the cellular mechanism related to the anti-seizure effects of low-frequency electrical stimulation).

Epilepsy affects about 1-2% of world population as a chronic neurological disease that is manifested by repeated and consecutive seizures (Grone and Baraban, Nat Neurosci 18(3):339-343, 2015). There is no definitive therapy for epilepsy and antiepileptic drugs cannot offer a permanent and definitive cure for epilepsy, and most epileptic patients become drug resistant (Sasa, J Pharmacol Sci 100(5):487-494, 2006). Surgery and removal of the epileptic focus is a substitute method for treating drug-resistant patients and epilepsy surgery of either side of the brain improves seizure control. Temporal lobectomy is the most common epilepsy surgery and is associated with high success rates. Other studies have reported higher success rates for carefully selected temporal lobe seizure patients. Some physicians still consider temporal lobectomy an extreme procedure, citing the risks of side effects, including loss of memory, visual disturbances, and emotional change, associated with the removal of brain tissue (Spencer, Lancet Neurol 1(6):375-382, 2002; Wiebe et al., N Engl J Med 345(5):311-318, 2001; Yasargil et al., J Neurosurg 112(1):168-185, 2010). Nowadays, direct electrical stimulation (in the form of low- or high-frequency stimulation) in the location involved in seizures is used as a potentially suitable treatment method for this destructive disease in both laboratory animals and humans (Goodman et al., Epilepsia 46(1):1-7, 2005; Richardson et al., Epilepsia 44(6):768-777, 2003; Velasco et al., Epilepsia 41(2):158-169, 2000). Low-frequency stimulation causes less damage to the epileptic area and surrounding neuronal structures compared to high-frequency stimulation, and it can be a suitable option for patients suffering from epilepsy (Goodman et al., Epilepsia 46(1):1-7, 2005). Since the cellular mechanism of this stimulation is not clearly known, the purpose of this review research was to investigate the anticonvulsive effects of low-frequency electrical stimulation and the probable cellular mechanism involved in it.

Antiepileptic effect of low-frequency electrical stimulation is waveform-dependent in hippocampal kindled mice

To investigate whether the waveform of electrical stimulus affects the antiepileptic effect of focal low-frequency stimulation (LFS). The antiepileptic effects of the LFS in sine, monophase square and biphase square waves were investigated in hippocampal kindled mice, respectively. Compared to the control group, sine wave focal LFS (30 s) inhibited seizure stages (2.85 ± 0.27 vs 4.75 ± 0.12, P<0.05), lowered incidence of generalized seizures (53.6% vs 96.5%, P<0.01) and reduced afterdischarge durations [(16.2 2 ± 1.69)s vs (30.29 ± 1.12)s, P<0.01] in hippocampal kindled mice, while monophase or biphase square wave LFS (30 s) showed no antiepileptic effect. Monophase square LFS (15 min) inhibited seizure stages (3.58 ± 0.16, P<0.05) and incidence of generalized seizures (66.7%,P<0.01), but had weaker inhibitory effect on hippocampal afterdischarge durations than sine wave LFS. In addition, pre-treatment and 3 s but not 10 s post-treatment with sine wave LFS resulted in suppression of evoked seizures (P<0.05 or P<0.01). The antiepileptic effect of LFS is dependent on its waveform. Sine wave may be optimal for closed-loop LFS treatment of epilepsy.