Involvement of GABAergic pathway on inhibition of subthalamic nucleus high-frequency stimulation of spontaneous firing activity in substantia nigra pars reticulata neurons in a rat model of Parkinson's disease

BACKGROUND： Subthalamic nucleus-high frequency stimulation （STN-HFS） plays an important role in the treatment of Parkinson＇s disease, but the mechanisms underlying STN-HFS remain unclear. Some studies have demonstrated that STN stimulation inhibits the firing activity of substantia nigra pars reticulata neurons. OBJECTIVE： To investigate the effects of different-frequency STN stimulation and microiontophoresis of gamma-aminobutyric acid （GABA） and its antagonist, bicuculline, on spontaneous firing activity in a rat model of Parkinson＇s disease, and to analyze the action pathway of high frequency stimulation in firing activity inhibition of substantia nigra pars reticulata neurons. DESIGN, TIME AND SETTING： This neuroelectrophysiological, animal experiment was performed at the Electrophysiology Laboratory of Liaoning Medical University, China from March to August 2008. MATERIALS： 6-hydroxydopamine （6-OHDA） （Sigma, USA）, A320R isolated stimulus and DAM80 preamplifier （World Precision Instruments, USA）, 6400A microiontophoresis apparatus （Dagan, USA）, and Spike 2 biological signal acquisition system （CED, UK） were used in this study. METHODS： A total of 20 Sprague Dawley rats were used to establish a Parkinson＇s disease model via injection of 6-OHDA into the right striatum. Electrical stimulation （0.06-ms width, 0.4-mA intensity 20-200-Hz frequency, 5-second train duration） was delivered to the subthalamic nucleus. Peripheral channels were separately filled with GABA （pH 3.5, 0.2 mol/L）, bicuculline （pH 4.0, 0.01 mol/L）, and NaCI （pH 7.0, 3 mol/L）. The electrode was positioned with a WK-2 microelectrode propulsion device, and was slowly inserted into the substantia nigra pars reticulata to record spontaneous firing activity of substantia nigra pars reticulata neurons. MAIN OUTCOME MEASURES： The number and firing rate of substantia nigra pars reticulata neurons which were either inhibited or excited were measured. RESULTS： Substantia nigra pars reticulata neurons were inhibited by STN stimulation. The proportion of inhibited substantia nigra pars reticulata neurons increased with increasing stimulation frequency. GABA had a tonic inhibitory effect on substantia nigra pars reticulata neurons. Microiontophoresis of bicuculline suppressed the inhibitory effect of STN-HFS on 67% （4/6） of substantia nigra pars reticulata neurons. CONCLUSION： STN-HFS ameliorated abnormal activity in substantia nigra pars reticulata neurons via the inhibitory effect of GABA treatment in a rat model of Parkinson＇s disease.

Towards frequency adaptation for delayed feedback deep brain stimulations

In neurodegenerative disorders such as Parkinson＇s disease （PD）, deep brain stimulation （DBS） is a desirable approach when the medication is less effective for treating the symptoms. DBS incorporates transferring electrical pulses to a specific tissue of the central nervous system, obtaining therapeutic results by modulating the neuronal activity of that region. DBS has certain advantages such as reversibility and adjustability features over medication, since the neuronal firing patterns can be recorded and used to alter the parameters of the DBS signal （Benabid et al., 2009）. One of the DBS indications is its ability to suppress the abnormal neuronal activity to treat symptoms like tremor, akinesia and dystonia.

Electrical stimulation upregulates angiopoietin-1/Tie-2 mRNA expression in a rat model of focal cerebral ischemia

Angiopoietin-1/tyrosine kinase with immunoglobulin and epidermal growth factor homology domains 2 （Tie-2） is a newly discovered signaling pathway of angiogenesis. Angiogenesis benefits recovery of neurological functions such as swallowing. In the present study, a rat model of dysphagia following stroke was induced by middle cerebral artery occlusion to investigate the influence of low frequency electrical stimulus with bidirectional square waves and triangular waves on angiopoietin-1/-13e-2 mRNA expression. Reverse transcription-polymerase chain reaction results showed that low frequency electrical stimulus significantly improved the neurological scores of the model rats, and increased angiopoietin-1/＇13e-2 mRNA expression. This demonstrates that low frequency electrical stimulation can ameliorate neurological function in rats with focal brain ischemia, potentially through regulation of angiopoietin-1/-13e-2 expression in the angiogenesis pathway.

Effect of low versus high frequency stimulation on freezing of gait and other axial symptoms in Parkinson patients with bilateral STN DBS:a mini-review

Some studies have shown that low frequency stimulation(LFS,most commonly 60 Hz),compared to high frequency stimulation(HFS,most commonly 130 Hz),has beneficial effects,short-term or even long-term,on improving freezing of gait(FOG)and other axial symptoms,including speech and swallowing function,in Parkinson disease(PD)patients with bilateral subthalamic nucleus deep brain stimulation(STN DBS).However,other studies failed to confirm this.It seems not clear what determines the difference in response to LFS.Differences in study design,such as presence or absence of FOG,exact LFS used(60 Hz versus 80 Hz),study size,open label versus randomized double blind assessment,retrospective versus prospective evaluation,medication On or Off state,total electric energy delivered maintained or not with the change in frequency,and the location of active contacts could all potentially affect the results.This mini-review goes over the literature with the aforementioned factors in mind,focusing on the effect of LFS versus HFS on FOG and other axial symptoms in PD with bilateral STN DBS,in an effort to extract the essential data to guide our clinical management of axial symptoms and explore the potential underlying mechanisms as well.Overall,LFS of 60 Hz seems to be consistently effective in patients with FOG at the usual HFS in regards to improving FOG,speech,swallowing function and other axial symptoms,though LFS could reduce tremor control in some patients.Whether LFS simply addresses the axial symptoms in the context of HFS or has other beneficial effects requires further studies,along with the mechanism.

Cochlear and Vestibular Functional Study in Patients with Sudden Deafness and Lyme Disease

Lyme disease (LD) and idiopathic sudden deafness (ISD) are supposed to be different diseases with different aetiologies. In an attempt to confirm this assumption, 10 patients with confirmed LD and 12 patients with ISD were consecutively included into the study. Further to the laboratory and audio logical investigation, a low frequency sound (LFS) stimulation on posturography was performed and evaluated. Patients with ISD had higher pure tone average (PTA) than patients with LD (PTA ISD/LD was 72 decibel (dB)/23 dB). There was no difference of vertigo between LD and ISD patients. Patients with ISD have more body sway velocity during the first stimulation than patients with LD. We conclude that the cochlear organ is more affected in ISD patients than in patients with LD. However, the vestibular organ seems to be affected in both diseases. ISD and LD are two different disease entities with different aetiologies but with common otological clinical signs.

Effects of low frequency external excitation on oil slug mobilization and flow in a water saturated capillary model

The present research is to experimentally study the joint effects of external pressure and vibratory excitations of low frequency on oil slug mobilization and flow in a capillary model.During and after the oil slug mobilization,the flow phenomena and pressure drop variation across the model are investigated.The distance travelled by the oil slug subjected to various external pressure and vibratory excitations are also studied.The experimental results obtained indicate that the external vibratory excitation acting on the model has positive effect on the flow and mobilization of the oil slug in the model.It is found in the research,with the application of the excitation,the contact angle between the oil slug and tube-wall is changed;the maximum pressure required to mobilize the oil slug is reduced accordingly;and the oil slug travel distance is increased in comparing with that without external excitations.This research contributes to the comprehension of improved liquid mobilization in porous media under the application of external excitations.The finding of the research is significant for studying the two-phase liquid flow in porous media subjected to external excitations and provides insights for Enhanced Oil Recovery with waterflooding and vibratory stimulations.

Non-Invasive Treatment to Grade 1 Essential Hypertension by Percutaneous Laser and Electric Pulse to Acupoint with Music:A Randomized Controlled Trial

Objective： To study a non-drug therapy for hypertension disease by combining percutaneous laser and electric pulse stimulation to acupoint with music, and to test the efficiency of the combining treatment to grade 1 essential hypertension. Methods： A total of 174 patients with grade 1 essential hypertension were randomly assigned to 3 groups with a random number table after Chinese medicine（CM） syndrome differentiation： the photoelectric and musical treatment group（Group 1, with a self-developed multi-mode audio frequency pulse photoelectric therapeutic apparatus）, acupuncture group（Group 2）, and oral placebo group（Group 3）, 58 cases per group. The curative effect of each group was evaluated by the changes of blood pressure and CM syndrome integral before and after treatment. Results： Compared with Group 3, there were significant decrease of blood pressure and CM syndrome integral in Group 1 and Group 2（P〈0.01）. Compared with Group 2, Group 1 showed the highest decrease in systolic pressure（P〈0.017）. The total effective rate of anti-hypertension in Group 1（91.38%, 53/58） was significantly higher than that in Group 2（74.13%, 43/58） and Group 3（18.97%, 11/58, P〈0.05 or P〈0.01）; and that in Group 2 was also significantly higher than that in Group 3（P〈0.01）. There were significant difference in the total effective rate of CM syndrome integral in both Group 1（93.10%, 54/58） and Group 2（84.48%, 49/58） as compared with Group 3（17.24%, 10/58, P〈0.01）, while there was no significant difference between Group 1 and Group 2（P〉0.05）. Conclusions： The multi-mode audio frequency pulse photoelectric therapeutic apparatus, combining music, laser and electric pulse stimulation, is clinically useful for grade 1 essential hypertension. This ＂three in one＂ therapy method is non-invasive, easy and simple to handle. It is expected to be popularized as a new alternative treatment.