Previous studies have shown that electroacupuncture (EA) promotes recovery of motor function in Parkinson's disease (PD). However the mechanisms are not completely understood. Clinically, the subthalamic nucleus (STN) is a critical target for deep brain stimulation treatment of PD, and vesicular glutamate transporter 1 (VGluT1) plays an important role in the modulation of glutamate in the STN derived from the cortex. In this study, a 6-hydroxydopamine (6-OHDA)-lesioned rat model of PD was treated with 100 Hz EA for 4 weeks. Immunohistochemical analysis of tyrosine hydroxylase (TH) showed that EA treatment had no effect on TH expression in the ipsilateral striatum or substantia nigra pars compacta, though it alleviated several of the parkinsonian motor symptoms. Compared with the hemi-parkinsonian rats without EA treatment, the 100 Hz EA treatment significantly decreased apomorphine-induced rotation and increased the latency in the Rotarod test. Notably, the EA treatment reversed the 6-OHDA-induced down-regulation of VGluT1 in the STN. The results demonstrated that EA alleviated motor symptoms and up-regulated VGluT1 in the ipsilateral STN of hemi-parkinsonian rats, suggesting that up-regulation of VGluT1 in the STN may be related to the effects of EA on parkinsonian motor symptoms via restoration of function in the cortico-STN pathway.
Adrenergic Agents ; toxicity ; Animals ; Apomorphine ; pharmacology ; Disease Models, Animal ; Dopamine Agonists ; pharmacology ; Electroacupuncture ; methods ; Functional Laterality ; drug effects ; Male ; Medial Forebrain Bundle ; injuries ; Motor Activity ; drug effects ; physiology ; Neurons ; drug effects ; metabolism ; Oxidopamine ; toxicity ; Parkinson Disease, Secondary ; chemically induced ; physiopathology ; therapy ; Rats ; Rats, Sprague-Dawley ; Subthalamic Nucleus ; drug effects ; metabolism ; pathology ; Tyrosine 3-Monooxygenase ; metabolism ; Up-Regulation ; drug effects ; physiology ; Vesicular Glutamate Transport Protein 1 ; metabolism

Aged ; Computed Tomography Angiography ; Deep Brain Stimulation ; adverse effects ; Female ; Hematoma, Subdural, Intracranial ; diagnosis ; etiology ; surgery ; Humans ; Subthalamic Nucleus ; physiology

PURPOSE: As Parkinson's disease (PD) can be considered a network abnormality, the effects of deep brain stimulation (DBS) need to be investigated in the aspect of networks. This study aimed to examine how DBS of the bilateral subthalamic nucleus (STN) affects the motor networks of patients with idiopathic PD during motor performance and to show the feasibility of the network analysis using cross-sectional positron emission tomography (PET) images in DBS studies. MATERIALS AND METHODS: We obtained [15O]H2O PET images from ten patients with PD during a sequential finger-to-thumb opposition task and during the resting state, with DBS-On and DBS-Off at STN. To identify the alteration of motor networks in PD and their changes due to STN-DBS, we applied independent component analysis (ICA) to all the cross-sectional PET images. We analysed the strength of each component according to DBS effects, task effects and interaction effects. RESULTS: ICA blindly decomposed components of functionally associated distributed clusters, which were comparable to the results of univariate statistical parametric mapping. ICA further revealed that STN-DBS modifies usage-strengths of components corresponding to the basal ganglia-thalamo-cortical circuits in PD patients by increasing the hypoactive basal ganglia and by suppressing the hyperactive cortical motor areas, ventrolateral thalamus and cerebellum. CONCLUSION: Our results suggest that STN-DBS may affect not only the abnormal local activity, but also alter brain networks in patients with PD. This study also demonstrated the usefulness of ICA for cross-sectional PET data to reveal network modifications due to DBS, which was not observable using the subtraction method.
Aged ; Brain/*radionuclide imaging ; Cross-Sectional Studies ; Deep Brain Stimulation/*methods ; Female ; Functional Laterality/*physiology ; Humans ; Male ; Middle Aged ; Parkinson Disease/radionuclide imaging/*therapy ; Positron-Emission Tomography ; Severity of Illness Index ; Subthalamic Nucleus/*physiopathology

We investigated the effect of propofol and fentanyl on microelectrode recording (MER) and its clinical applicability during subthalamic nucleus (STN) deep brain stimulation (DBS) surgery. We analyzed 8 patients with Parkinson's disease, underwent bilateral STN DBS with MER. Their left sides were done under awake and then their right sides were done with a continuous infusion of propofol and fentanyl under local anesthesia. The electrode position was evaluated by preoperative MRI and postoperative CT. The clinical outcomes were assessed at six months after surgery. We isolated single unit activities from the left and the right side MERs. There was no significant difference in the mean firing rate between the left side MERs (38.7+/-16.8 spikes/sec, n=78) and the right side MERs (35.5+/-17.2 spikes/sec, n=66). The bursting pattern of spikes was more frequently observed in the right STN than in the left STN. All the electrode positions were within the STNs on both sides and the off-time Unified Parkinson's Disease Rating Scale part III scores at six months after surgery decreased by 67% of the preoperative level. In this study, a continuous infusion of propofol and fentanyl did not significantly interfere with the MER signals from the STN. The results of this study suggest that propofol and fentanyl can be used for STN DBS in patients with advanced Parkinson's disease improving the overall experience of the patients.
Aged ; Anesthetics, Intravenous/*pharmacology ; *Deep Brain Stimulation ; Electrodes, Implanted ; Female ; Fentanyl/*pharmacology ; Humans ; Magnetic Resonance Imaging ; Male ; Microelectrodes ; Middle Aged ; Parkinson Disease/*prevention & control ; Propofol/*pharmacology ; Severity of Illness Index ; Subthalamic Nucleus/*drug effects/physiology ; Tomography, X-Ray Computed

Adult ; Deep Brain Stimulation ; Essential Tremor ; physiopathology ; therapy ; Female ; Humans ; Male ; Middle Aged ; Subthalamic Nucleus ; physiology

OBJECTIVETo observe the modulatory effect of subthalamic nucleus (STN) on activity of motor cortex during exhausting exercise.

METHODSElectrocorticogram (ECoG) and local field potentials (LFPs) recording techniques were applied simultaneously to observe the dynamic changes of oscillations in sensorimotor area and STN of rat during exhausting exercise.

RESULTSRats ran well initiatively with treadmill at the beginning of the exercise, about 45 min (45 +/- 11.5) later, movement capacity reduced. Corresponding electrical property showed that STN activity increased significantly while activity of cortex decreased significantly. Subsequently rats continued exercise with minor external stimulation utill exhaustion. Activity of ECoG reached the minimum under exhausting stations (P < 0.01), while the activity of LFPs changed insignificantly (P > 0.05).

CONCLUSIONDuring the exhausting exercise, the cortex activity was extensively depressed with the development of fatigue, while the activity of STN increased significantly at the early stage of fatigue, STN took part in the modulation of central fatigue through negative induction. And the increase of STN activity may be one of the key measures accounting for protective inhibition.

Animals ; Cerebral Cortex ; physiology ; Electrophysiological Phenomena ; physiology ; Male ; Neurons ; physiology ; Physical Conditioning, Animal ; physiology ; Physical Exertion ; physiology ; Rats ; Rats, Wistar ; Subthalamic Nucleus ; physiology

We compared the surgical outcome with electrode positions after bilateral subthalamic nucleus (STN) stimulation surgery for Parkinson's disease. Fifty-seven patients treated with bilateral STN stimulations were included in this study. Electrode positions were determined in the fused images of preoperative MRI and postoperative CT taken at six months after surgery. The patients were divided into three groups: group I, both electrodes in the STN; group II, only one electrode in the STN; group III, neither electrode in the STN. Unified Parkinson's Disease Rating Scale (UPDRS), Hoehn and Yahr stage, and activities of daily living scores significantly improved at 6 and 12 months after STN stimulation in both group I and II. The off-time UPDRS III speech subscore significantly improved (1.6 +/- 0.7 at baseline vs 1.3 +/- 0.8 at 6 and 12 months, P < 0.01) with least L-dopa equivalent daily dose (LEDD) (844.6 +/- 364.1 mg/day at baseline; 279.4 +/- 274.6 mg/day at 6 months; and 276.0 +/- 301.6 mg/day at 12 months, P < 0.001) at 6 and 12 months after STN deep brain stimulation (DBS) in the group I. Our findings suggest that the better symptom relief including speech with a reduced LEDD is expected in the patients whose electrodes are accurately positioned in both STN.
Adult ; Aged ; Antiparkinson Agents/adverse effects/*therapeutic use ; Combined Modality Therapy ; *Deep Brain Stimulation/adverse effects/instrumentation/methods ; *Electrodes, Implanted ; Female ; Humans ; Levodopa/adverse effects/therapeutic use ; Magnetic Resonance Imaging ; Male ; Middle Aged ; Parkinson Disease/drug therapy/*therapy ; Severity of Illness Index ; Subthalamic Nucleus/*physiology ; Treatment Outcome

AIMTo investigate the neuroprotective effects of lesion and high frequency stimulation(HFS) of the subthalamic nucleus (SIN) on the substantia nigra pars compacta(SNc) neurons and its probable mechanism.

METHODSThe PD models were induced by unilateral administration of 6-hydroxydopamine into right substantia nigra in rats. After the high-frequence stimulation to SIN and injection of ibotenic acid to STN on PD rats, the changes of behavior were observed. The substantia nigra neurons were detected by using special-dyeing, TUNEL techniques and immunohistochemistry methods.

RESULTSIn the stimulation group, the apoptotic rate was significantly lower than PD model group and lesion group (P < 0.05). Compared with normal rats, model group and lesion one had the similar results of expression of Bcl-2, Bax and their ratio, which were lower expression of Bcl-2, higher expression of Bax and the decrease of their ratio (P < 0.05). In the stimulation group, the expression of Bcl-2 and Bcl-2/Bax were much higher than model group and lesion group. The number of apoptotic neurons of rats in lesion group was smaller than model ones (P < 0.05), but there was no significant difference in expression of Bcl-2, Bax and their ratio (P > 0.05).

CONCLUSIONLesion or HFS of STN have the neuroprotective effects on SNc neurons of PD rats, and HFS has a better long-term effect.

Animals ; Electric Stimulation ; Male ; Neurons ; physiology ; Oxidopamine ; Parkinson Disease, Secondary ; chemically induced ; physiopathology ; therapy ; Proto-Oncogene Proteins c-bcl-2 ; metabolism ; Rats ; Rats, Sprague-Dawley ; Substantia Nigra ; physiopathology ; Subthalamic Nucleus ; physiopathology ; bcl-2-Associated X Protein ; metabolism

AIMTo research the spontaneous firing activities during different-frequency stimulation of subthalamic nucleus and microelectrophoresis GABA, Glu and their antagons respectively, approaching the mechanism of DBS in the treatment of Parkinson's disease further.

METHODSUsing extracellular recording to investigate the effect of different-frequency stimulation of STN and microelectrophoresis several drugs on the spontaneous firing activities of the SNr neurons.

RESULTSFor STN stimulation at low frequency, there was no difference on the spontaneous firing activities of SNr neurons between pro-stimulation and meta-stimulation (P > 0.05). With the increasing of stimulation frequency, most of the SNr neurons were inhibited. While during the STN stimulation frequency at high-frequency, the firing rates of inhibited SNr neurons were changed (P < 0.05). Glu had catatonic excitement effect on the SNr neurons, whereas GABA had tonic inhibition effect. 80% of SNr neurons which were inhibited by STN-HFS were not inhibited by STN-HFS on the basis of excitatory effect of BIC.

CONCLUSIONTo treat the motor symptoms of PD, when SIN is selected as the target nucleus, the electrical stimulation with high-frequency should be chosen. It is possible that SIN-HFS modulate the activity of SNr by inhibitory effect of GABA predominantly.

Action Potentials ; physiology ; Animals ; Electric Stimulation ; Electrophoresis ; methods ; Glutamic Acid ; administration & dosage ; pharmacology ; Male ; Neurons ; physiology ; Parkinson Disease ; physiopathology ; therapy ; Rats ; Rats, Sprague-Dawley ; Substantia Nigra ; physiology ; Subthalamic Nucleus ; physiology ; gamma-Aminobutyric Acid ; administration & dosage ; pharmacology

The present study was designed to investigate the function and mechanism of high-frequency stimulation (HFS) of the parafascicular nucleus (PF) used as a therapeutic approach for Parkinson's disease (PD). PD rat model was built by injecting 6-hydroxydopamine (6-OHDA) into the substartia nigra pars compacta of adult male Sprague-Dawley rats. Using the ethological methods, we examined the effect of electrical stimulation of PF on the apomorphine-induced rotational behavior in PD rats. Moreover, Electrophysiological recordings were made in rats to investigate the effects of electrical stimulation of PF on the neuronal activities of the subthalamic nucleus (STN) and the ventromedial nucleus (VM). Our results showed that one week after HFS (130 Hz, 0.4 mA, 5 s) of PF, there was significant improvement in apomorphine-induced rotational behavior in PD rats. HFS of PF caused an inhibition of the majority of neurons (84%) recorded in the STN in PD rats. The majority of cells recorded in the VM of the thalamus responded to the HFS with an increase in their unitary discharge activity (81%). These effects were in a frequency-dependent manner. Only stimulus frequencies above 50 Hz were effective. Furthermore, employing microelectrophoresis, we demonstrated that glutamatergic and GABAergic afferent nerve fibers converged on the same STN neurons. These results show that the HFS of PF induces a reduction of the excitatory glutamatergic output from the PF which in turn results in deactivation of STN neurons. The reduction in tonic inhibitory drive from the basal ganglia induces a disinhibition of activity in the VM, a motor thalamic nucleus. In conclusion, the results suggest that HFS of PF may produce a therapeutic effect in PD rats, which is mediated by the nuclei of PF, STN and VM.
Action Potentials ; physiology ; Animals ; Electric Stimulation ; Intralaminar Thalamic Nuclei ; physiopathology ; Male ; Neurons ; physiology ; Parkinson Disease ; physiopathology ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Subthalamic Nucleus ; physiopathology ; Ventral Thalamic Nuclei ; physiopathology