Role Of Spinal Cord Research Articles

MicroRNA-101a-3p mimic ameliorates spinal cord ischemia/reperfusion injury.

miR-101a-3p is expressed in a variety of organs and tissues and plays a regulatory role in many diseases, but its role in spinal cord ischemia/reperfusion injury remains unclear. In this study, we established a rat model of spinal cord ischemia/reperfusion injury by clamping the aortic arch for 14 minutes followed by reperfusion for 24 hours. Results showed that miR-101a-3p expression in L4-L6 spinal cord was greatly decreased, whereas MYCN expression was greatly increased. Dual-luciferase reporter assay results showed that miR-101a-3p targeted MYCN. MYCN immunoreactivity, which was primarily colocalized with neurons in L4-L6 spinal tissue, greatly increased after spinal cord ischemia/reperfusion injury. However, intrathecal injection of an miR-101a-3p mimic within 24 hours before injury decreased MYCN, p53, caspase-9 and interleukin-1β expression, reduced p53 immunoreactivity, reduced the number of MYCN/NeuN-positive cells and the number of necrotic cells in L4-L6 spinal tissue, and increased Tarlov scores. These findings suggest that the miR-101a-3p mimic improved spinal ischemia/reperfusion injury-induced nerve cell apoptosis and inflammation by inhibiting MYCN and the p53 signaling pathway. Therefore, miR-101a-3p mimic therapy may be a potential treatment option for spinal ischemia/reperfusion injury.

Lapatinib alleviates TOCP-induced axonal damage in the spinal cord of mouse

Neuregulin-1 (NRG1), a family of EGF-like factors that activates ErbB receptors, can regulate the proliferation, migration, and myelinating of Schwann cells. We previously reported that NRG1/ErbB signal is responsible for organophosphate (OP)-induced delayed neuropathy (OPIDN) in hens, a susceptive animal model to neuropathic organophosphorous compounds. Our previous study discovered that a neuropathic OP, tri-o-cresyl phosphate (TOCP) activated NRG1/ErbB signaling pathway in both spinal cord and sciatic nerves of hens during the formation of OPIDN and lapatinib, a non-selective antagonist of ErbB1 and ErbB2 receptors, alleviated the toxicity. In this study, we intended to further look into the potential role of NRG1 in the pathogenesis of TOCP-induced axon damage in spinal cord and sciatic nerves and whether lapatinib could also rescue this damage in mice, an OPIDN-resistant animal model. The results revealed that no obvious toxic signs were observed after single TOCP exposure. However, slight histopathological wreck in lumbar spinal cord and sciatic nerves was found following TOCP intoxication, and the damage in sciatic nerves was characterized by axon degeneration of myelin sheath but not the loss of neural skeleton. Only histopathological damage induced by TOCP in spinal cord could be prevented by lapatinib. The translational expression of NRG1/ErbB signaling molecules was analyzed by both in vivo and in vitro studies. In general, NRG1/ErbB pathway was activated by TOCP while combined treatment with lapatinib attenuated TOCP-induced NRG1/ErbB signaling cascade. The results implied that NRG1/ErbB system may predominately play functional role in spinal cord (central nervous system) but not in sciatic nerves (peripheral nervous system) of mouse subjected to neurotoxic OP, which was confirmed by the study in vitro that lapatinib was not able to attenuate TOCP-induced neurotoxicity in rodent Schwann cell line RSC 96 cells.

Role of spinal cord TRAF6/NF-κB signaling pathway in development of diabetic neuropathic pain in rats

Objective To evaluate the role of spinal cord tumor necrosis factor receptor-associated factor 6 (TRAF6)/nuclear factor kappa B(NF-κB)signaling pathway in the development of diabetic neuropathic pain(DNP)in rats. Methods Clean-grade healthy adult male Sprague-Dawley rats, aged 2 months, weighing 180-230 g, in which IT catheters were implanted, were used in this study.Streptozotocin 60 mg/kg was intraperitoneally injected after IT catheterization to establish the model of DNP.Twelve DNP rats were divided into 2 groups (n=6 each) by a random number table method: DNP group and DNP plus TRAF6 inhibitor group (group DTR). Another 6 age-matched Sprague-Dawley rats were used as normal control group(group NC). The rats in group DC and group DTR received IT injection of dimethyl sulfoxide 10 μl and TRAF6 inhibition 10 μg, respectively, once a day for 7 consecutive days starting from day 21 after establishing the model.The mechanical paw withdrawal threshold (MWT) was determined before establishing the model(T1), on 7, 14 and 21 days after establishing the model(T2-4), and on 1, 4 and 7 days after IT injection (T5-7). The rats were sacrificed after the last MWT measurement, and the L3-5 segments of the spinal cord were removed for determination of the expression of TRAF6 and NF-κB p65 by Western blot. Results Compared with group NC, the MWT at T3-7 in group DC and at T3-6 in group DTR was significantly decreased, and the expression of spinal TRAF6 and NF-κB p65 was up-regulated in DC and DTR groups (P<0.05). Compared with group DC, the MWT was significantly increased at T6-7, and the expression of spinal TRAF6 and NF-κB p65 was down-regulated in group DTR (P<0.05). Conclusion Spinal cord TRAF6/NF-κB signaling pathway is involved in the development of DNP in rats. Key words: Spinal cord; Tumor necrosis factor receptor-associated peptides and proteins; NF-kappa B; Diabetes mellitus; Neuralgia

Robust spinal cord resting-state fMRI using independent component analysis-based nuisance regression noise reduction.

Physiological noise reduction plays a critical role in spinal cord (SC) resting-state fMRI (rsfMRI). To reduce physiological noise and increase the robustness of SC rsfMRI by using an independent component analysis (ICA)-based nuisance regression (ICANR) method. Retrospective. Ten healthy subjects (female/male = 4/6, age = 27 ± 3 years, range 24-34 years). 3T/gradient-echo echo planar imaging (EPI). We used three alternative methods (no regression [Nil], conventional region of interest [ROI]-based noise reduction method without ICA [ROI-based], and correction of structured noise using spatial independent component analysis [CORSICA]) to compare with the performance of ICANR. Reduction of the influence of physiological noise on the SC and the reproducibility of rsfMRI analysis after noise reduction were examined. The correlation coefficient (CC) was calculated to assess the influence of physiological noise. Reproducibility was calculated by intraclass correlation (ICC). Results from different methods were compared by one-way analysis of variance (ANOVA) with post-hoc analysis. No significant difference in cerebrospinal fluid (CSF) pulsation influence or tissue motion influence were found (P = 0.223 in CSF, P = 0.2461 in tissue motion) in the ROI-based (CSF: 0.122 ± 0.020; tissue motion: 0.112 ± 0.015), and Nil (CSF: 0.134 ± 0.026; tissue motion: 0.124 ± 0.019). CORSICA showed a significantly stronger influence of CSF pulsation and tissue motion (CSF: 0.166 ± 0.045, P = 0.048; tissue motion: 0.160 ± 0.032, P = 0.048) than Nil. ICANR showed a significantly weaker influence of CSF pulsation and tissue motion (CSF: 0.076 ± 0.007, P = 0.0003; tissue motion: 0.081 ± 0.014, P = 0.0182) than Nil. The ICC values in the Nil, ROI-based, CORSICA, and ICANR were 0.669, 0.645, 0.561, and 0.766, respectively. ICANR more effectively reduced physiological noise from both tissue motion and CSF pulsation than three alternative methods. ICANR increases the robustness of SC rsfMRI in comparison with the other three methods. 2 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2018;47:1421-1431.

Anti-inflammatory and Antiapoptotic Effect of Interleukine-18 Binding Protein on the Spinal Cord Ischemia-Reperfusion Injury

We investigated the anti-inflammatory and antiapoptotic effects of interleukin-18 binding protein (IL-18BP) on spinal cord ischemia/reperfusion (I/R) injury in rats. Twenty-one adult male rats were divided into three groups: sham, I/R, and I/R+IL-18BP. Proinflammatory cytokines were determined in rat blood samples by using ELISA, while apoptosis was immunohistochemically evaluated in spinal cord tissue using caspase 3. Both IL-18 and TNF-α were significantly decreased in the IL-18BP group compared to that in the sham group. The highest caspase 3 levels were observed in the I/R group, while the lowest levels were found in the sham group. The mean Tarlov score of the I/R group was significantly lower than that of the sham group. However, the mean Tarlov score of the IL-18BP group was significantly higher than that of the I/R group. The results of the current study demonstrate that IL-18BP plays both anti-inflammatory and antiapoptotic roles in spinal cord I/R injury.

Oxidative phosphorylated neurofilament protein M protects spinal cord against ischemia/reperfusion injury.

Previous studies have shown that neurofilament protein M expression is upregulated in the early stage of spinal cord ischemia/reperfusion injury, indicating that this protein may play a role in the injury process. In the present study, we compared protein expression in spinal cord tissue of rabbits after 25 minutes of ischemia followed by 0, 12, 24, or 48 hours of reperfusion with that of sham operated rabbits, using proteomic two-dimensional gel electrophoresis and mass spectrometry. In addition, the nerve repair-related neurofilament protein M with the unregulated expression was detected with immunohistochemistry and western blot analysis. Two-dimensional gel electrophoresis and mass spectrometry showed that, compared with the sham group, upregulation of protein expression was most significant in the spinal cords of rabbits that had undergone ischemia and 24 hours of reperfusion. Immunohistochemical analysis revealed that neurofilament protein M was located in the membrane and cytoplasm of neuronal soma and axons at each time point after injury. Western blot analysis showed that neurofilament protein M expression increased with reperfusion time until it peaked at 24 hours and returned to baseline level after 48 hours. Furthermore, neurofilament protein M is phosphorylated under oxidative stress, and expression changes were parallel for the phosphorylated and non-phosphorylated forms. Neurofilament protein M plays an important role in spinal cord ischemia/reperfusion injury, and its functions are achieved through oxidative phosphorylation.

Neuromodulation in treatment of hypertension by acupuncture: A neurophysiological prospective

Hypertension is a major public health problem affecting over one billion individuals worldwide. This disease is the result of complex interactions between genetic and life-style factors and the central nervous system. Sympathetic hyperactivity has been postulated to be present in most forms of hypertension. Pharmaceutical therapy for hypertension has not been perfected, often requires a multidrug regimen, and is associated with adverse side effects. Acupuncture, a form of somatic afferent nerve stimulation has been used to treat a host of cardiovascular diseases such as hypertension. It has long been established that the two major contributors to systemic hypertension are the intrarenal reninangiotensin system and chronic activation of the sympathetic nervous system. A number of important studies on the baroreflex response and its response to acupuncture are discussed. The inhibitory effects of acupuncture on the rostral ventrolateral medulla (rVLM) reduces sympathetic nerve activity and blood pressure suggesting overactivity of the angiotensin system in this nucleus may play a role in the maintenance of hypertension. Our experimental studies have shown that electroacupuncture stimulation activates neurons in the arcuate nucleus, ventro-lateral gray, and nucleus raphe to inhibit the neural activity in the rVLM in a model of visceral reflex stimulation-induced hypertension. The significant role of spinal cord opioids and nociceptin are also reviewed. Although clinical studies of acupuncture to date have met some success, they are rarely scientifically robust and do not feature randomization and long-term follow up. Based on a great deal of basic scientific evidence, large trials are desperately needed to study the effects of acupuncture on the hyperensive man.

Role of Spinal Cord in Regulating Mouse Kidney: A Virally Mediated Trans-synaptic Tracing Study

To determine the spinal innervation and neuronal connections is important for studying renal metabolic responses. In this study, the spinal cords of 10 adult male C57BL/6J strain mice were mapped retrograde using injections of pseudorabies virus (PRV)-614. The virus, injected into the kidney, was specifically transported to the spinal cord. At 5 days after injection of the PRV-614, PRV-614-positive cells were found in the intermediolateral cell column, the intercalates nucleus, or the central autonomic nucleus of spinal cord segments T4-L1, and most PRV-614-labeled cells were found in the T9 segment. Our results revealed neuroanatomical circuits between kidney and the spinal intermediolateral cell column neurons.

Expression and ultrastructural localization of Mint2 in the spinal cord of rats

Mint protein family, as adaptor molecules, contains three members, Mint1, Mint2 and Mint3. Although Mint3 is ubiquitously expressed, Mint1 and Mint2 have been reported to express specifically in neuron. Here we demonstrated Mint1 and Mint2 expression pattern in rat spinal cord. The protein level of Mint2 was found to be higher than that of Mint1 in rat spinal by western blot. In an attempt to know Mint2 distribution in the spinal cord of rat, in situ hybridization was carried out, Mint2 mRNA was showed to be ubiquitously distributed in cervical, thoracic and lumbar sections of rat spinal cord, and high intensive signal was detected in motor neurons. These were further confirmed by fluorescent immunohistochemistry, Mint2 was also found to exist throughout gray matter especially motor neurons where Mint2 was mainly located in perikaryon, however, Mint1 was showed to be relatively lower. By electron microscope, Mint2 was found to be mainly located in vesicles in perikaryon in motor neuron of lumbar section, and at the same time Mint2 was located in axons in myelin and presynaptic terminals. These data suggest that Mint2 may play more important role in spinal cord than the other two family members.

Inhibition of the MEK/ERK pathway reduces microglial activation and interleukin-1-beta expression in spinal cord ischemia/reperfusion injury in rats

Ischemic spinal cord injury is a serious complication of aortic surgery. Although the extracellular signal-regulated kinases 1 and 2 are generally regarded as related to cell proliferation and survival, increasing evidence suggests that the role of the extracellular signal-regulated kinase pathway in ischemia/reperfusion injury is much more sophisticated. Spinal cord ischemia in rats was induced by occluding the thoracic descending aorta with a balloon catheter introduced through a femoral artery, accompanied by concomitant exsanguination. Rats in the control group were given dimethyl sulfoxide (vehicle) before undergoing spinal cord ischemia/reperfusion injury. In the U0126-treated group, rats were pretreated with a specific inhibitor of the mitogen-activated protein kinase/extracellular signal-regulated kinases 1 and 2, U0126, to inhibit extracellular signal-regulated kinases 1 and 2 phosphorylation. The sham-operated rats underwent aortic catheterization without occlusion. Parameters, including neurologic performance, neuronal survival, inflammatory cell infiltration, and interleukin-1beta production in the spinal cords, were compared between groups. Early extracellular signal-regulated kinases 1 and 2 phosphorylation was observed after injury in the control group, followed by abundant microglial accumulation in the infarct area and increased interleukin-1beta expression. In the U0126 group, U0126 treatment completely blocked extracellular signal-regulated kinases 1 and 2 phosphorylation. Microglial activation and spinal cord interleukin-1beta levels were significantly reduced. Neuronal survival and functional performance were improved. The mitogen-activated protein kinase/extracellular signal-regulated kinase pathway may play a noxious role in spinal cord ischemia/reperfusion injury by participating in inflammatory reactions and cytokine production. Targeting this pathway may be of potential value in terms of therapeutic intervention.

843 CAN RECHARGEABLE NEUROSTIMULATORS PLAY A ROLE IN SPINAL CORD STIMULATION THERAPY IN PATIENTS WITH REFRACTORY ANGINA PECTORIS?

European Journal of PainVolume 10, Issue S1 p. S219a-S219 843 CAN RECHARGEABLE NEUROSTIMULATORS PLAY A ROLE IN SPINAL CORD STIMULATION THERAPY IN PATIENTS WITH REFRACTORY ANGINA PECTORIS? C. Scherer, C. Scherer ESES-Unit, Dep. of Anaesthesiology and Intensive Care, Odense University Hospital, DenmarkSearch for more papers by this authorT. Enggaard, T. Enggaard ESES-Unit, Dep. of Anaesthesiology and Intensive Care, Odense University Hospital, DenmarkSearch for more papers by this authorC. Andersen, C. Andersen ESES-Unit, Dep. of Anaesthesiology and Intensive Care, Odense University Hospital, DenmarkSearch for more papers by this author C. Scherer, C. Scherer ESES-Unit, Dep. of Anaesthesiology and Intensive Care, Odense University Hospital, DenmarkSearch for more papers by this authorT. Enggaard, T. Enggaard ESES-Unit, Dep. of Anaesthesiology and Intensive Care, Odense University Hospital, DenmarkSearch for more papers by this authorC. Andersen, C. Andersen ESES-Unit, Dep. of Anaesthesiology and Intensive Care, Odense University Hospital, DenmarkSearch for more papers by this author First published: 13 January 2012 https://doi.org/10.1016/S1090-3801(06)60846-XRead the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat No abstract is available for this article. Volume10, IssueS1September 2006Pages S219a-S219 RelatedInformation

Stimulus-transcription coupling and immediate-early genes: Correlations and molecular mechanisms

Z immerman and Herdegen provide an interesting, if somewhat fast-paced, review of cellular immediate early genes (clEGs) and their potential roles in spinal cord and dorsal root ganglion neurons during nociception and nerve injury. It has now been unequivocal ly demonstrated that activation of a wide variety of neural pathways by either natural, pathological, or pharmacological stimuli modifies neuronal gene expression. In many cases, the process of gene regulation appears to commence with the activation of several classes of proteins whose names are based on historical association with drosophi la molecular genetics (transacting factors), or by analogy with virology (cellular immediate early genes). These proteins generally share the common property of recognizing and binding to specific sequences of DNA and, thereby regulating gene expression. Generally these proteins act to control gene transcript ion and, the clEGs are members of a broader class of proteins called transcription factors all of which govern gene transcription within the cell nuc leus . 2'14'17'18'21'25'28'30 One of the questions that is apparently still under debate is whether induct ion of clEGs reflects increased neural activity. In my opinion, the answer is a definite, but qualified, yes. The qual i f icat ion depends on how neural activity is defined. If one thinks only in terms of action potentials, then a correspondence between activity and gene expression, especially clEGs, does not necessarily apply. A microelec-

The role of spinal cord 5-HT 1A and 5-HT 1B receptors in the modulation of a spinal nociceptive reflex

The role of the 5-hydroxytryptamine (5-HT) receptor subtypes in the spinal cord in the regulation of nociception is unknown. This study examined whether administration of different 5-HT 1 receptor agonists into the spinal subarachnoid space of mice modulates the nociceptive tail-flick reflex, and whether effects on the tail-flick reflex involve changes in tail skin temperature. The tail-flick latencies (the time needed to evoke the tail-flick reflex by noxious radiant heat) were significantly increased after intrathecal (i. th.) injection of 5-HT (10–20 μg), the 5-HT 1A/5-HT 1B receptor agonist 5-methoxy-N,N-dimethyltryptamine (5-MeODMT, 10–20 μg), the selective 5-HT 1A receptor agonist 8-hydroxy-2-di-n-propylamino)tetralin (8-OH-DPAT, 20 μg), and after i.th. injection of 1(m-chlorophenyl)piperazine (mCPP, 5–20 μg) and 5-methoxy-3(1,2,3,6-tetrahydropyridin-4-yl)-1H-indole (RU 24969, 5–20 μg) which have high affinity for the 5-HT 1B receptors. None of the 5-HT 1 receptor agonists had the ability to change the tail skin temperature. The results show that in the mouse i.th. injection of both 5-HT 1A and 5-HT 1B receptor agonists has the ability to inhibit the tail-flick reflex without interfering with the tail skin temperature.