scholarly journals Effects of Ozone on Hippocampus BDNF and Fos Expressions in Rats with Chronic Compression of Dorsal Root Ganglia

2021 ◽  
Vol 2021 ◽  
pp. 1-10
Author(s):  
Lingling Zhu ◽  
Yanxiu Wang ◽  
Xiaowen Lin ◽  
Xu Zhao ◽  
Zhi jian Fu

The effects of ozone on hippocampal expression levels of brain-derived neurotrophic factor (BDNF) and c-fos protein (Fos) were evaluated in rats with chronic compression of dorsal root ganglia (CCD). Forty-eight adult female Sprague-Dawley rats were randomly divided into the following 4 groups ( n = 12 ): sham operation (sham group), CCD group, CCD with 20 μg/ml of ozone ( CCD + A O 3 group), and CCD with 40 μg/ml of ozone ( CCD + B O 3 group). Except the sham group, unilateral L5 dorsal root ganglion (DRG) compression was performed on all other groups. On days 1, 2, and 4 after the operation, the CCD + A O 3 and CCD + B O 3 groups were injected with 100 μl of ozone with concentrations of 20 and 40 μg/ml, respectively. Thermal withdrawal latencies (TWLs) and mechanical withdrawal thresholds (MWTs) were measured at various time points before and after the operation. BDNF and Fos expressions were examined in the extracted hippocampi using immunohistochemistry. The TWLs and MWTs of CCD model rats that received ozone were lower with decreased BDNF and increased Fos expression levels, on day 21 after the operation, compared to those of the sham group ( P < 0.05 ). The TWLs and MWTs of the CCD + A O 3 and CCD + B O 3 groups were higher with increased BDNF and decreased Fos expression levels, on day 21 after the operation, compared to those of the CCD group ( P < 0.05 ). The TWLs were longer and the MWTs were higher in the CCD + B O 3 group at each time point with increased BDNF and decreased Fos expression levels, on day 21 after the operation, compared to those of the CCD + A O 3 group ( P < 0.05 ). Our results revealed that ozone can relieve the neuropathic pain caused by the pathological neuralgia resulting from DRG compression in rats. The mechanism of action for ozone is likely associated with changes in BDNF and Fos expression levels in the hippocampus.

2020 ◽  
Author(s):  
Cheng-Fu wan ◽  
Bo-Han zhang ◽  
Dao-Song Dong ◽  
Tao Song

Abstract Background: Neuropathic pain (NP) can be treated effectively using pulsed radiofrequency (PRF). NP development and maintenance involves the essential neurotransmitter chemokine c-c motif ligand 2 (CCL2). The present study aimed to determine whether PRF regulated CCL2 expression in sciatic nerve injury (SNI) model rats.Methods: Sprague-Dawley rats were divided randomly into a sham group, an SNI group, and a PRF group. In the PRF group, L5 dorsal root ganglia received PRF treatment. After paw withdrawal mechanical threshold (PWMT) was examined, the expression levels of CCL2 and nuclear factor kappa B (NF-κB) in spinal dorsal horn were determined.Results: The PWMT in PRF group increased significantly compared with that of the SNI group (P < 0.05). The CCL2 and NF-κB expression levels in the PRF group were significant lower than those in the SNI group (P < 0.05).Conclusion: NP was effectively alleviated by PRF-mediated reductions in CCL2 expression via inhibition of NF-κB activation in the spinal cord of SNI model rats.


2012 ◽  
Vol 2012 ◽  
pp. 1-6 ◽  
Author(s):  
Myeoung Hoon Cha ◽  
Taick Sang Nam ◽  
Yongho Kwak ◽  
Hyejung Lee ◽  
Bae Hwan Lee

The production of proinflammatory cytokines including interleukin-1 (IL-1), interleukin-6 (IL-6), and tumor necrosis factor-α(TNF-α) plays a key role in chronic pain such as neuropathic pain. We investigated changes in cytokine expression in injured peripheral nerves and dorsal root ganglia (DRG) following electroacupuncture (EA) treatment. Neuropathic pain was induced by peripheral nerve injury to the left hind limb of Sprague-Dawley rats under pentobarbital anesthesia. Two weeks later, the nerve-injured rats were treated by EA for 10 minutes. The expression levels of IL-1β, IL-6, and TNF-αin peripheral nerves and DRG of neuropathic rats were significantly increased in nerve-injured rats. However, after EA, the cytokine expression levels were noticeably decreased in peripheral nerves and DRG. These results suggest that EA stimulation can reduce the levels of proinflamtory cytokines elevated after nerve injury.


2016 ◽  
Vol 4;19 (4;5) ◽  
pp. E589-E600
Author(s):  
Salahadin Abdi

Background: Chemotherapy-induced neuropathic pain is difficult to treat. Pentoxifylline inhibits the production of inflammatory cytokines including tumor necrosis factor α (TNF-α) and interleukin 1β (IL-1β). Objective: The aims of our study were to investigate the analgesic and preventive effects of pentoxifylline on paclitaxel-induced neuropathic pain in rats and to identify its mechanisms of action. Study Design: Controlled animal study. Methods: Neuropathic pain was induced with intraperitoneally injected paclitaxel on 4 alternate days in male Sprague-Dawley rats. Pentoxifylline was administered systemically as a single injection and a continuous infusion before or after the injection of paclitaxel. The mechanical threshold for allodynia was measured by using von Frey filaments. Protein levels and localization of inflammatory cytokines were performed by using Western blotting and immunohistochemistry, respectively. Results: After the rats developed neuropathic pain behavior, a single intraperitoneal injection and continuous infusion of pentoxifylline ameliorated paclitaxel-induced mechanical allodynia. In addition, systemic infusion of pentoxifylline in the early phase of the development of pain behavior delayed the onset of paclitaxel-induced pain behavior. Paclitaxel increased the levels of the catalytic subunit α of protein kinase A, phosphorylated nuclear factor κB, TNF-α, and IL-1β in the lumbar dorsal root ganglia. Pentoxifylline decreased the paclitaxel-induced TNF-α and IL1β levels. In addition, IL-1β was expressed in neurons and satellite cells in the lumbar dorsal root ganglia after paclitaxel. Limitations: Although this study was performed in the animal model by well-designed manner, clinical study will be needed to confirm the analgesic effect of pentoxifylline. Conclusion: Pentoxifylline alleviated chemotherapy-induced neuropathic pain in rats by reducing the levels of inflammatory cytokines in dorsal root ganglia and may be effective chemotherapyinduced neuropathic pain in patients. Key words: Chemotherapy, chronic pain, inflammatory cytokines, neuropathic pain, paclitaxel, pain behavior, pain treatment, pentoxifylline, phosphodiesterase inhibitor


2014 ◽  
Vol 8 (1) ◽  
pp. 69-73 ◽  
Author(s):  
Kazuyuki Watanabe ◽  
Karin Larsson ◽  
Björn Rydevik ◽  
Shin-ichi Konno ◽  
Claes Nordborg ◽  
...  

Purpose: It has been assumed that nucleus pulposus-induced activation of the dorsal root ganglion (DRG) may be related to an activation of sodium channels in the DRG neurons. In this study we assessed the expression of Nav 1.8 and Nav 1.9 following disc puncture. Method: Thirty female Sprague-Dawley rats were used. The L4/L5 disc was punctured by a needle (n=12) and compared to a sham group without disc puncture (n=12) and a naive group (n=6). At day 1 and 7, sections of the left L4 DRG were immunostained with anti-Nav 1.8 and Nav 1.9 antibodies. Result: At day 1 after surgery, both Nav 1.8-IR neurons and Nav 1.9-IR neurons were significantly increased in the disc puncture group compared to the sham and naive groups (p<0.05), but not at day 7. Conclusion: The findings in the present study demonstrate a neuronal mechanism that may be of importance in the pathophysiology of sciatic pain in disc herniation.


2020 ◽  
Author(s):  
Yuan Li ◽  
Heng Zhang ◽  
Ning-Tao Ren ◽  
Chao Chen ◽  
Peng Qi ◽  
...  

Abstract Background: Previous studies demonstrate that long-tern microgravity induces multi-organ injury and dysfunction, including the dorsal root ganglia (DRG) damage. This study investigated oral pyruvate protective effects on lumbar 5 (L5) DRG nerve tissues in rats subjected to hindlimb unweighting (HU).Results: Male Sprague-Dawley rats were randomly assigned to four groups (n=10): control group (Group CON), suspension group (Group SUS), normal saline group (Group SAL) and sodium pyruvate group (Group PYR), respectively. The rats of SUS, SAL and PYR groups were simulated with microgravity by tail suspension of HU for 8 weeks. Rats in Groups SAL and PYR fed with normal saline and pyruvate saline, respectively. Histopathological and immunofluorescence examinations were conducted and levels of glial cell line-derived neurotrophic factor (GDNF), glial fibrillary acidic protein (GFAP), ATP and ATPase were measured in DRG tissues; L5 spinal cord scans were also carried out in rats following HU. Results showed that the HU resulted in significant alterations in DRG nerve tissues’ structure and function in Groups SUS and SAL, whereas morphological changes were not significantly distinguished between Group PYR and Group CON; GDNF, GFAP, ATP and ATPase levels were mostly preserved in Group PYR, but still worse than in Group CON. The significance of oral pyruvate protection against DRG injury following HU and the dose and formula of oral pyruvate solutions were discussed for use in astronauts’ spaceflight.Conclusions: oral pyruvate effectively protected L5 DRG from pathological alterations and dysfunction induced by the HU in rats. Further studies and clinical trials are warranted.


2017 ◽  
Vol 11 (4) ◽  
pp. 556-561 ◽  
Author(s):  
Jun Sato ◽  
Kazuhide Inage ◽  
Masayuki Miyagi ◽  
Yoshihiro Sakuma ◽  
Kazuyo Yamauchi ◽  
...  

<sec><title>Study Design</title><p>An experimental animal study.</p></sec><sec><title>Purpose</title><p>To evaluate effects of anti-vascular endothelial growth factor (VEGF) on the content and distribution of the calcitonin gene-related peptide (CGRP) in the dorsal ganglia in a rat model.</p></sec><sec><title>Overview of Literature</title><p>Increased expression of VEGF in degenerative disc disease increases the levels of inflammatory cytokines and nerve ingrowth into the damaged discs. In animal models, increased levels of VEGF can persist for up to 2 weeks after an injury.</p></sec><sec><title>Methods</title><p>Through abdominal surgery, the dorsal root ganglia (DRG) innervating L5/L6 intervertebral disc were labeled (FluoroGold neurotracer) in 24, 8-week old Sprague Dawley rats. The rats were randomly allocated to three groups of eight rats each. The anti-VEGF group underwent L5/6 intervertebral disc puncture using a 26-gauge needle, intradiscal injection of 33.3 µg of the pegaptanib sodium, a VEGF165 aptamer. The control-puncture group underwent disc puncture and intradiscal injection of 10 µL saline solution, and the sham-surgery group underwent labeling but no disc puncture. Two rats in each group were sacrificed on postoperative days 1, 7, 14, and 28 after surgery. L1–L6 DRGs were harvested, sectioned, and immunostained to detect the content and distribution of CGRP.</p></sec><sec><title>Results</title><p>Compared with the control, the percentage of CGRP-positive cells was lower in the anti-VEGF group (<italic>p</italic>&lt;0.05; 40.6% and 58.1% on postoperative day 1, 44.3% and 55.4% on day 7, and 42.4% and 59.3% on day 14). The percentage was higher in the control group compared with that of the sham group (<italic>p</italic>&lt;0.05; sham group, 34.1%, 40.7%, and 33.7% on postoperative days 1, 7, and 14, respectively).</p></sec><sec><title>Conclusions</title><p>Decreasing CGRP-positive cells using anti-VEGF therapy provides fundamental evidence for a possible therapeutic role of anti-VEGF in patients with discogenic lower back pain.</p></sec>


2017 ◽  
Vol 43 (6) ◽  
pp. 2479-2488 ◽  
Author(s):  
Xiaoying Dong ◽  
Can Wang ◽  
Jingqi Zhang ◽  
Siyue Wang ◽  
Hongjian Li ◽  
...  

Background/Aims: Cholecystokinin (CCK) is expressed in cardiomyocytes and may also play an important role in cardiovascular regulation. Clinical studies have shown that plasma CCK levels are an independent marker of cardiovascular mortality in cardiac disease. However, whether the development of postinfarction heart failure is associated with changes in CCK expression is unknown. Methods: To investigate CCK expression patterns and the association between CCK expression and heart functional parameters, we randomized male Sprague-Dawley rats into myocardial infarction (MI) or sham operation (SO) groups. CCK expression levels were assessed by western blotting, immunohistochemistry, real-time polymerase chain reaction (PCR), and enzyme-linked immunosorbent assay (ELISA) at different time points (2, 4 or 6 weeks) after surgery. Brain natriuretic peptide (BNP) concentrations were determined using Western blotting and ELISA, myocardial morphology was assessed by microscopy. Results: Plasma CCK and BNP levels were significantly increased in all the MI groups compared with the corresponding SO groups. However, the degree to which myocardial CCK mRNA and protein expression levels were increased the MI groups compared with the SO groups was greater in the 4- and 6-week groups than in the 2-week group. Furthermore, plasma CCK levels were positively correlated with BNP concentrations and left ventricular end-systolic diameter (LVDs) and significantly negatively correlated with the ejection fraction (EF) and shortening fraction (SF) in model animals. Conclusions: Heart failure progression after infarction is associated with upregulated CCK levels; thus, CCK may be useful as a novel marker of heart failure.


Author(s):  
Qi Li ◽  
Zi-yu Zhu ◽  
Jian Lu ◽  
Yu-Chieh Chao ◽  
Xiao-xin Zhou ◽  
...  

AbstractPerioperative sleep disturbance is a risk factor for persistent pain after surgery. Clinical studies have shown that patients with insufficient sleep before and after surgery experience more intense and long-lasting postoperative pain. We hypothesize that sleep deprivation alters L-type calcium channels in the dorsal root ganglia (DRG), thus delaying the recovery from post-surgical pain. To verify this hypothesis, and to identify new predictors and therapeutic targets for persistent postoperative pain, we first established a model of postsurgical pain with perioperative sleep deprivation (SD) by administering hind paw plantar incision to sleep deprivation rats. Then we conducted behavioral tests, including tests with von Frey filaments and a laser heat test, to verify sensory pain, measured the expression of L-type calcium channels using western blotting and immunofluorescence of dorsal root ganglia (an important neural target for peripheral nociception), and examined the activity of L-type calcium channels and neuron excitability using electrophysiological measurements. We validated the findings by performing intraperitoneal injections of calcium channel blockers and microinjections of dorsal root ganglion cells with adeno-associated virus. We found that short-term sleep deprivation before and after surgery increased expression and activity of L-type calcium channels in the lumbar dorsal root ganglia, and delayed recovery from postsurgical pain. Blocking these channels reduced impact of sleep deprivation. We conclude that the increased expression and activity of L-type calcium channels is associated with the sleep deprivation-mediated prolongation of postoperative pain. L-type calcium channels are thus a potential target for management of postoperative pain.


2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Yasuki Nakada ◽  
Kenji Onoue ◽  
Tomoya Nakano ◽  
Satomi Ishihara ◽  
Takuya Kumazawa ◽  
...  

Abstract Soluble Flt-1 (sFlt-1), an endogenous antagonist of the proatherogenic cytokine placental growth factor, is decreased in chronic kidney disease (CKD), leading to atherosclerotic progression. In this study, we investigated the effect of AST-120, an oral carbon adsorbent which can remove uremic toxins, on sFlt-1 expression levels and atherosclerosis progression. Atherosclerotic apolipoprotein E-deficient mice underwent a 5/6 nephrectomy (5/6 NR) or a sham operation (sham) at 8 weeks of age and were then treated or not with oral AST-120 for 12 weeks. sFlt-1 expression levels and the degree of atherosclerosis were assessed at 22 weeks of age in each of the four groups (sham; n = 7, 5/6 NR; n = 10, sham + AST-120: n = 8, 5/6 NR + AST-120; n = 8). The expression levels of sFlt-1 mRNA in the kidney were significantly lower in the 5/6 NR group than in the sham group, but AST-120 treatment prevented this decrease in sFlt-1 levels. Similarly, the atherosclerotic plaque area of the thoracoabdominal aorta was significantly larger in the 5/6 NR group than in the sham group, and AST-120 treatment prevented this increase in atherosclerosis. AST-120 could, therefore, be used as a therapeutic to treat atherosclerosis in patients with CKD.


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