scholarly journals Ozone Exposure Induces Metabolic Disorders and NAD+ Depletion Through PARP1 Activation in Spinal Cord Neurons

2020 ◽  
Vol 7 ◽  
Author(s):  
Shulin Ma ◽  
Xu Zhao ◽  
Cong Zhang ◽  
Panpan Sun ◽  
Yun Li ◽  
...  

Background and Objective: Ozone therapy has shown therapeutic efficacy in different disorders particularly low back pain (LBP). However, ozone therapy has been associated with toxic effects on the respiratory, endocrine, cardiovascular systems as well as nervous system because of its strong oxidizing capacity. Recent studies have reported possible associations between ozone exposure and metabolic disorders, but the findings are controversial and little is known on the mechanisms of action. This study aims to investigate the cytotoxic effects of ozone exposure and possible mechanism of action in the animal model.Methods: Wistar neonate rats with the age of 24 h after birth were sacrificed by cervical dislocation under general anesthesia, then immersed in 75% alcohol and iodophor for 5 min, respectively. The spinal cord was isolated and cut to samples of ~1 mm3 and prepared for further experiments. The spinal cord neurons (SCNs) were exposed to ozone at different concentrations and then cultured in 96-well plates with glass bottom for 7 days. The cell viability, ATP levels and the NAD+ concentration were determined and compared between the different experimental groups and the control group.Results: Analyses of the data by non-targeted liquid chromatography-mass spectrometry (LC-MS) analysis determined the metabolic disorder in SCNs following the ozone exposure. Moreover, our assessments showed that ozone exposure resulted in DNA damage, poly (ADP)-ribose polymerase-1 (PARP1) excessive activation, nicotinamide adenine dinucleotide (NAD+) depletion and decrease of ATP level in SCNs. The PARP1 inhibitor can inhibit the cytotoxic effect of ozone to SCNs without inhibiting the activation of AMP-activated protein kinase (AMPK). Our findings revealed that the cytotoxic effects of ozone to SCNs might be mediated by excessive PARP1 activation and subsequent NAD+ depletion. Moreover, using PARP1 inhibitor can protect SCNs from cytotoxic effects of ozone by preventing NAD+ depletion during ozone exposure.Conclusion: Ozone exposure seems to induce metabolic disorders and NAD+ depletion through excessive PARP1 activation in SCNs.

2015 ◽  
Vol 16 (2) ◽  
pp. 225-234 ◽  
Author(s):  
Alessandra Cristina Francischini de Carvalho ◽  
Maria Rita Pacheco ◽  
Silvana Martinez Baraldi-Artoni ◽  
Annita Morais Girardi

The aim of this work was to analyze the neuron morphology and morphometry of cervical, thoracic and lumbar areas of nonsymptomatic seropositive dogs’ spinal cord for toxoplasmosis. Twenty indefinite-breed adult dogs were used; ten dogs were healthy, with negative serology for toxoplasmosis, and were used as the control group (group 1), and ten dogs were nonsymptomatic but seropositive for toxoplasmosis (group 2). After the microtomy, with interval of 100 micrometers (µm), the histological 5-µm-thick cuts were dyed by hematoxylin-eosin and Masson's trichrome techniques. The glass slides were analyzed under light microscope to examine the neuron morphology. The parameters considered for the morphometric analysis were area, perimeter, maximum diameter, minimum diameter and shape factor of cytoplasm and nucleus of neuron. The results were statistically analyzed by Student’s t test at 5% probability level. The morphological characteristics between the two groups were similar and according to literature. The morphometric results showed that there were changes in neurons size and structure, and increase and loss of star shape were noticed in seropositive animals. The results suggest that the neurons of these dogs, yet nonsymptomatic, can have lost their conductor function.


1999 ◽  
Vol 81 (6) ◽  
pp. 2620-2626 ◽  
Author(s):  
Johannes Nebe ◽  
Andrea Ebersberger ◽  
Horacio Vanegas ◽  
Hans-Georg Schaible

Effects of ω-agatoxin IVA, a P-type calcium channel antagonist, on the development of spinal neuronal hyperexcitability caused by knee inflammation in rats. Both N- and P-type high-threshold calcium channels are located presynaptically in the CNS and are involved in the release of transmitters. To investigate the importance of P-type calcium channels in the generation of inflammation-evoked hyperexcitability of spinal cord neurons, electrophysiological recordings were made from wide-dynamic-range neurons with input from the knee joint in the anesthetized rat. The responses of each neuron to innocuous and noxious pressure onto the knee and the ankle were continuously assessed before and during the development of an inflammation in the knee joint induced by the injections of K/C into the joint cavity. The specific antagonist at P-type calcium channels ω-agatoxin was administered into a 30-μl trough on the spinal cord surface above the recorded neuron. In most neurons the application of ω-agatoxin before induction of inflammation slightly enhanced the responses to pressure onto the knee and ankle or left them unchanged. Two different protocols were then followed. In the control group (13 rats) only Tyrode was administered to the spinal cord during and after induction of inflammation. In these neurons the responses to mechanical stimuli applied to both the inflamed knee and to the noninflamed ankle showed a significant increase over 4 h. In the experimental group (12 rats) ω-agatoxin was applied during knee injection and in five 15-min periods up to 180 min after kaolin. This prevented the increase of the neuronal responses to innocuous pressure onto the knee and to innocuous and noxious pressure onto the ankle; only the responses to noxious pressure onto the knee were significantly enhanced during development of inflammation. Thus the development of inflammation-evoked hyperexcitability was attenuated by ω-agatoxin, and this suggests that P-type calcium channels in the spinal cord are involved in the generation of inflammation-evoked hyperexcitability of spinal cord neurons. Finally, when ω-agatoxin was administered to the spinal cord 4 h after the kaolin injection, i.e., when inflammation-evoked hyperexcitability was fully established, the responses to innocuous and noxious pressure onto the knee were reduced by 20–30% on average. The shift in the effect of ω-agatoxin, from slight facilitation or no change of the responses before inflammation to inhibition in the state of hyperexcitability, indicates that P-type calcium channels are important for excitatory synaptic transmission involved in the maintenance of inflammation-evoked hyperexcitability.


Author(s):  
Semeleva E.V. ◽  
Blinova E.V. ◽  
Zaborovsky A.V. ◽  
Vasilkina O.V. ◽  
Shukurov A.S.

In this work, we studied the pharmacological activity of zinc and magnesium salts of 2-aminoethanesulfonic acid in white non-linear male rats with amyotrophic lateral sclerosis, which was modeled by neurotoxicantsimplication into the pelvic part of spinal cord. After the reproduction of the pathology in animals, the indices of motor activity were recorded in the Rotarod test, and morphological studies of spinal cord sections stained according to Nisl in the Belshovsky modification were carried out. It was shown that the magnesium salt of 2-aminoethanesulfonic acid (compound LHT-317) to a greater extent reduces the development of motor disorders in experimental animals compared with the control group on the 4th day of observation. The course of intravenous administration of the studied compounds of 2-aminoethanesulfonic acid did not inhibit morphological changes in the spinal cord that develop in degenerative-dystrophic pathology of the central nervous system: connections. Moreover, if, against the background of treatment with zinc salt, the total area of motor zones in animals of the experimental group exceeded that of control rats, then the number of motoneurons did not differ from the control.


2019 ◽  
Vol 24 (2) ◽  
pp. 121-126 ◽  
Author(s):  
V. G. Atrushkevich ◽  
L. Yu. Orekhova ◽  
O. O. Yanushevich ◽  
E. Yu. Sokolova ◽  
E. S. Loboda

Relevance: to indentify if periodontal treatment which is presented by photoactivated disinfection (PAD) adjunctively to scaling and root planing (SRP) yield better outcomes than ozone therapy as an adjunct to SRP in periodontitis.Materials and methods: we examined 57 (mean age 49,3 ± 1,02) patients with chronic periodontitis, divided into groups, SRP + PAD, SRP + ozone therapy and SRP alone. Subgingival plaque samples were subjected to DNA extraction and real time PCR amplifcation for detection Porphyromonas gingivalis (Pg), Prevotella intermedia (Pi), Tannerella forsythensis (Tf), Treponema denticola (Td), Aggregatibacter actinomycetemcomitans (Aa). The amount of periodontopathogens and clinical parameters including plaque index, clinical attachment loss, pocket depth, bleeding on probing were measured at baseline, after 40, 90 and 180 days.Results: the results in groups of PAD+SRP and ozone therapy+SRP showed an improvement in all clinical parameters PI, BOP, PD, CAL and the quantity of Pg, Td and Tf compared to the control group during an observation period.Conclusion: the results showed additional benefts from PAD and ozone therapy as an adjunctive treatment to SRP for patients of chronic periodontitis.


2019 ◽  
Vol 18 (1) ◽  
pp. 52-62 ◽  
Author(s):  
Antonio Ibarra ◽  
Erika Mendieta-Arbesú ◽  
Paola Suarez-Meade ◽  
Elisa García-Vences ◽  
Susana Martiñón ◽  
...  

Background: The chronic phase of Spinal Cord (SC) injury is characterized by the presence of a hostile microenvironment that causes low activity and a progressive decline in neurological function; this phase is non-compatible with regeneration. Several treatment strategies have been investigated in chronic SC injury with no satisfactory results. OBJECTIVE- In this proof-of-concept study, we designed a combination therapy (Comb Tx) consisting of surgical glial scar removal plus scar inhibition, accompanied with implantation of mesenchymal stem cells (MSC), and immunization with neural-derived peptides (INDP). Methods: This study was divided into three subsets, all in which Sprague Dawley rats were subjected to a complete SC transection. Sixty days after injury, animals were randomly allocated into two groups for therapeutic intervention: control group and animals receiving the Comb-Tx. Sixty-three days after treatment we carried out experiments analyzing motor recovery, presence of somatosensory evoked potentials, neural regeneration-related genes, and histological evaluation of serotoninergic fibers. Results: Comb-Tx induced a significant locomotor and electrophysiological recovery. An increase in the expression of regeneration-associated genes and the percentage of 5-HT+ fibers was noted at the caudal stump of the SC of animals receiving the Comb-Tx. There was a significant correlation of locomotor recovery with positive electrophysiological activity, expression of GAP43, and percentage of 5-HT+ fibers. Conclusion: Comb-Tx promotes motor and electrophysiological recovery in the chronic phase of SC injury subsequent to a complete transection. Likewise, it is capable of inducing the permissive microenvironment to promote axonal regeneration.


Cells ◽  
2021 ◽  
Vol 10 (1) ◽  
pp. 143
Author(s):  
Ganchimeg Davaa ◽  
Jin Young Hong ◽  
Tae Uk Kim ◽  
Seong Jae Lee ◽  
Seo Young Kim ◽  
...  

Exercise training is a traditional method to maximize remaining function in patients with spinal cord injury (SCI), but the exact mechanism by which exercise promotes recovery after SCI has not been identified; whether exercise truly has a beneficial effect on SCI also remains unclear. Previously, we showed that epigenetic changes in the brain motor cortex occur after SCI and that a treatment leading to epigenetic modulation effectively promotes functional recovery after SCI. We aimed to determine how exercise induces functional improvement in rats subjected to SCI and whether epigenetic changes are engaged in the effects of exercise. A spinal cord contusion model was established in rats, which were then subjected to treadmill exercise for 12 weeks. We found that the size of the lesion cavity and the number of macrophages were decreased more in the exercise group than in the control group after 12 weeks of injury. Immunofluorescence and DNA dot blot analysis revealed that levels of 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC) in the brain motor cortex were increased after exercise. Accordingly, the expression of ten-eleven translocation (Tet) family members (Tet1, Tet2, and Tet3) in the brain motor cortex also elevated. However, no macrophage polarization was induced by exercise. Locomotor function, including Basso, Beattie, and Bresnahan (BBB) and ladder scores, also improved in the exercise group compared to the control group. We concluded that treadmill exercise facilitates functional recovery in rats with SCI, and mechanistically epigenetic changes in the brain motor cortex may contribute to exercise-induced improvements.


2021 ◽  
Vol 49 (5) ◽  
pp. 030006052110161
Author(s):  
Jing Li ◽  
Qiao-Ping Li ◽  
Bi-Hong Yang

Objective The study aim was to analyse the effect of participatory continuous nursing using the WeChat platform on the complications, family function and compliance of patients with spinal cord injuries. Methods This was a randomized controlled trial. Seventy-eight patients with stable disease treated by internal fixation were enrolled in the study from August 2017 to August 2019 and assigned equally to an observation group and a control group. The control group received regular care from the time of discharge. The observation group used the WeChat platform to participate in continuous care. Results Six months after discharge, the continuous nursing group had a significantly lower incidence of pressure ulcers, urinary tract infections, joint contractures and muscle atrophy than the control group. The continuous nursing group showed a significant improvement in family function level and compliance behaviour at 3 and 6 months after discharge. Conclusion A participation-based continuous nursing intervention using the WeChat platform can reduce the incidence of pressure ulcers, urinary tract infections, joint contracture and muscle atrophy; improve patient family function; and promote healthy compliance behaviour.


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