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Neuroprotective Potential of Gentongping in Rat Model of Cervical Spondylotic Radiculopathy Targeting PPAR-? Pathway.

ABSTRACT: Cervical spondylotic radiculopathy (CSR) is the most general form of spinal degenerative disease and is characterized by pain and numbness of the neck and arm. Gentongping (GTP) granule, as a classical Chinese patent medicine, has been widely used in curing CSR, whereas the underlying mechanism remains unclear. Therefore, the aim of this study is to explore the pharmacological mechanisms of GTP on CSR. The rat model of CSR was induced by spinal cord injury (SCI). Our results showed that GTP could significantly alleviate spontaneous pain as well as ameliorate gait. The HE staining and Western blot results showed that GTP could increase the quantity of motoneuron and enhance the activation of peroxisome proliferator-activated receptor gamma (PPAR-?) in the spinal cord tissues. Meanwhile, immunofluorescence staining analysis indicated that GTP could reduce the expression of TNF-? in the spinal cord tissues. Furthermore, the protein level of Bax was decreased whereas the protein levels of Bcl-2 and NF200 were increased after the GTP treatment. These findings demonstrated that GTP might modulate the PPAR-? pathway by inhibiting the inflammatory response and apoptosis as well as by protecting the cytoskeletal integrity of the spinal cord, ultimately play a neuroprotective role in CSR.

SUBMITTER: Sun W

PROVIDER: S-EPMC5694586 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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Neuroprotective Potential of Gentongping in Rat Model of Cervical Spondylotic Radiculopathy Targeting PPAR-<i>γ</i> Pathway.

Sun Wen W Zheng Kang K Liu Bin B Fan Danping D Luo Hui H Qu Xiaoyuan X Li Li L He Xiaojuan X Yi Jianfeng J Lu Cheng C

Journal of immunology research 20171105

Cervical spondylotic radiculopathy (CSR) is the most general form of spinal degenerative disease and is characterized by pain and numbness of the neck and arm. Gentongping (GTP) granule, as a classical Chinese patent medicine, has been widely used in curing CSR, whereas the underlying mechanism remains unclear. Therefore, the aim of this study is to explore the pharmacological mechanisms of GTP on CSR. The rat model of CSR was induced by spinal cord injury (SCI). Our results showed that GTP coul ...[more]

PMID: 29230425

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Project description:BackgroundCervical spondylosis is a very common disorder and cervical spondylotic radiculopathy (CSR) is the most common form of spinal degenerative disease. Its clinical manifestations focus on pain and numbness of the neck and arm as well as restricted movement of the neck, which greatly affect the patient's life and work. The orthopedic of traditional Chinese medicine (TCM) theory holds that the basic pathologic change in spinal degenerative diseases is the imbalance between the dynamic system and the static system of the cervical spine. Based on this theory, some Chinese physicians have developed a balance chiropractic therapy (BCT) to treat CSR, which has been clinically examined for more than 50 years to effectively cure CSR. The purpose of this study is to evaluate the therapeutic effect and safety of BCT on CSR and to investigate the mechanism by which the efficacy is achieved.Methods/designWe propose a multicenter, parallel-group, randomized controlled trial to evaluate the efficacy and safety of BCT for CSR. Participants aged 18 to 65 years, who are in conformity with the diagnostic criteria of CSR and whose pain score on a Visual Analog Scale (VAS) is more than 4 points and less than 8 points, will be included and randomly allocated into two groups: a treatment group and a control group. Participants in the treatment group will be treated with BCT, while the control group will receive traction therapy (TT). The primary outcome is pain severity (measured with a VAS). Secondary outcomes will include cervical curvature (measured by the Borden Index), a composite of functional status (measured by the Neck Disability Index, NDI), patient health status (evaluated by the SF-36 health survey) and adverse events (AEs) as reported in the trial.DiscussionIf BCT can relieve neck pain without adverse effects, it may be a novel strategy for the treatment of CSR. Furthermore, the mechanism of BCT for CSR will be partially elucidated.Trial registrationClinical Trials.gov Identifier: NCT02705131 . Registered on 9 March 2016.

Project description:IntroductionCervical spondylotic radiculopathy (CSR) is the most common pattern of cervical spondylosis, which is a serious and common degenerative disease. Both acupotomy and acupuncture have been widely used clinically to treat CSR in China with satisfied efficacy. However, there is no systematic review comparing the effectiveness of these two therapies. The aim of this study is to compare the therapeutic efficacy and safety between acupotomy and acupuncture for patients with CSR to provide evidence for clinical practice.Methods and analysisThe following electronic databases will be searched: Web of Science, PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure , China Biology Medicine disc, Wanfang Database and Chinese Scientific Journal Database (VIP). The randomised controlled trials of acupotomy versus acupuncture with/without additional treatment for CSR will be searched in the databases from their inception to December 2018 by two researchers independently. Visual analogue scale, symptom score and neck disability index will be assessed as the primary outcomes. The total effective rate, curative rate, adverse events and amount of rescue medication used will be assessed as the secondary outcomes. The Review Manager 5.3 will be used for meta-analysis and the evidence level will be assessed by using the method for Grading of Recommendations Assessment, Development and Evaluation. Continuous outcomes will be presented as the weighted mean difference or standardised mean difference with 95% CI, whereas dichotomous data will be expressed as relative risk with 95%?CI. If the included studies have existing heterogeneity (p<0.05), then a random-effects model will be used. Otherwise, we will calculate using a fixed-effects model.Ethics and disseminationEthical approval is not required because no primary data are collected. This review will be published in a peer-reviewed journal and will be presented at an international academic conference for dissemination.Prospero registration numberCRD42019117348.

Project description:Objective To explore the clinical effect and operating skills of channel assisted Cervical Key Hole technology combined with Ultrasonic Bone Osteotome (CKH-UBO) in the treatment of single segment cervical spondylotic radiculopathy (CSR). Methods From June 2018 to June 2020, 14 patients diagnosed with CSR and treated with channel assisted CKH-UBO were collected. The duration of the disease, the length of the incision, the operation time, the amount of bleeding during the operation, the length of hospitalization and the complications were recorded. The Range Of Motion (ROM) and the stability of the surgical segment were recorded before and after the operation. Visual analog scale (VAS), neck disability index (NDI) and modified macnab efficacy evaluation criteria were used to evaluate the surgical efficacy. Results The operative segments of the enrolled patients were all lower cervical vertebrae. The average incision length was 2.0 ± 0.1 cm, the operation time was 42.2 ± 5.7 min, the intraoperative bleeding volume was 32.7 ± 4.1 ml, and the hospital stay was 5.6 ± 1.2 days. There was no difference in ROM between preoperative and 3 months and 1 year after operation (P > 0.05), and all patients did not have segmental instability. The VAS scores of neck pain before surgery, 3 days after surgery, 3 months after surgery, and 1 year after surgery were 5.6 ± 1.2, 1.6 ± 0.6, 1.1 ± 0.7, 0.6 ± 0.5, and the VAS scores of upper limb pain were 6.2 ± 1.2, 1.7 ± 0.7, 1.1 ± 0.6, 0.6 ± 0.5. The NDI scores of upper limb pain before surgery, 3 days after surgery, 3 months after surgery, and 1 year after surgery were 36.7 ± 3.5, 9.8 ± 2.4, and 3.9 ± 1.5, 1.8 ± 1.0, The VAS and NDI scores at all follow-up time points after operation were significantly lower than those before operation (P < 0.001). One year after operation, the curative effect was evaluated according to the modified macnab evaluation standard, and the excellent and good rate was 100%. The complication rate was 6.25%. Conclusion Channel assisted CKH-UBO for single segment CSR has the advantages of short operation time, reliable clinical effect, high safety and low complication rate, which is worthy of clinical promotion.

Project description:Sagittal cervical alignment is a clinically related feature in patients suffering from chronic cervical spondylotic radiculopathy (CSR). We designed this randomized trial to explore the effects of cervical lordosis (CL) correction in thirty chronic lower CSR patients with CL < 20°. Patients were assigned randomly into two equal groups, study (SG) and control (CG). Both groups received neck stretching and exercises and infrared radiation; additionally, the SG received cervical extension traction. Treatments were applied 3× per week for 10 weeks after which groups were followed for 3 months and 2 years. The amplitude of dermatomal somatosensory evoked potentials (DSSEPS), CL C2−C7, and pain scales (NRS) were measured. The SG had an increase in CL post-treatment (p < 0.0001), this was maintained at 3 months and 2 years. No statistical improvement in CL was found for the CG. A significant reduction in NRS for SG after 10 weeks of treatment with non-significant loss of change at 3 months and continued improvement at 2 years was found. CG had less significant improvement in post-treatment NRS; the 3-month and 2-year measures revealed significant worsening in NRS. An inverse linear correlation between increased CL and NRS was found (r = −0.49; p = 0.005) for both groups initially and maintained in SG at the final 2-year follow-up (r = −0.6; p = 0.01). At 10 weeks, we found significant improvements in DSSEPS for both groups (p < 0.0001). We identified a linear correlation between initial DSSEPs and CL for both groups (p < 0.0001), maintained only in the SG at the final follow-up for all levels (p < 0.0001). Improved CL in the SG correlated with significant improvements in nerve root function and pain rating in patients with CSR at short and long-term follow-up. These observed effects indicate that clinicians involved in the treatment of patients with symptoms of cervical degenerative disorders should add sagittal curve correction to their armamentarium of rehabilitation procedures for relevant patient populations.

Project description:MethodsTwenty patients with CSM and 17 controls were recruited. Clinical scores of modified Japanese Orthopedic Association (mJOA) and Nurick were collected. MRI based compression grades such as cord distortion were assessed. Hand dysfunction was tested using a custom motorized apparatus. Subject's forearm was placed in a cast and positioned such that their metacarpophalangeal (MCP) joint was vertically aligned with the motor shaft. Surface electromyographic sensors were placed on flexor digitorum superficialis (FDS) and extensor digitorum communis muscles. Hyperreflexia was measured as the FDS muscle activation during reflex when the MCP joint was moved from flexion to extension at 300°/sec. Proprioception was quantified as the angle of detection in absence of visual or auditory cues (subjects were blindfolded and given noise-cancelling headphones). Strength was measured as the maximum isometric force at the MCP joint. 2-sample t-test (p<0.05) were performed to assess significant differences in reflexes, proprioception and strength among patients and controls (SPSS software version 24).ResultsPatients reported higher Nurick (1.90±1.0 vs 0±0, p<0.001) and lower mJOA scores (14.3±1.9 vs 18.0±0, p<0.001) as compared to controls. Similarly, patients with CSM had increased reflexes (peak FDS EMG) (0.073±0.096 vs. 0.014±0.010, p = 0.019). Patient proprioception was significantly worse; mean angle of detection was greater than twice as high in patients (9.6± 9.43°) compared to controls (4.0± 2.3°), p = 0.022. MRI based compression ratio (CR) was a significant predictor of hyperreflexia, CR<0.44 resulted in steep increase in reflex activity. Fifteen of the 20 patients who completed follow up testing at 6 months after surgery show substantial clinical improvement in reflexes and proprioceptive angle, while repeated testing in controls were unchanged.ConclusionIn conclusion, hyperreflexia and decline in proprioception are the main drivers of hand disability in patients with CSM. Of multiple scales, only a select few MRI scales (such as compression ratio) were predictive of increased reflexes. The study describes a pre-clinical testing apparatus to quantitatively and objectively assess primary presenting symptoms in CSM. This pilot apparatus has the potential to evaluate treatment efficacy through repeated testing. Objective testing of hand dysfunction can help inform the design of clinically feasible devices, guide MRI biomarker analysis, and improve our understanding of the progression of neurological injury in this patient population.

Dataset Information

Neuroprotective Potential of Gentongping in Rat Model of Cervical Spondylotic Radiculopathy Targeting PPAR-? Pathway.

Publications

Neuroprotective Potential of Gentongping in Rat Model of Cervical Spondylotic Radiculopathy Targeting PPAR-<i>γ</i> Pathway.

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