Nitric oxide in the injured spinal cord: Synthases cross-talk, oxidative stress and inflammation

Conti, Alfredo; Miscusi, Massimo; Cardali, Salvatore; Germanò, Antonino; Suzuki, Hisanori; Cuzzocrea, Salvatore; Tomasello, Francesco

doi:10.1016/j.brainresrev.2007.01.013

Cited by 135 publications

(101 citation statements)

References 108 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Cell death and neuron degeneration, which occur after the injury, are a consequence of an increase in reactive oxygen species and NO production. NO is a unique molecule involved in a variety of physiological processes in the CNS [65]. The effects of NO on spinal cord damage are correlated with several factors, such as concentration of NO production, activity of different synthase isoforms, cellular source of production, and time of release [35].…”

Section: Discussionmentioning

confidence: 99%

B-Cell Depletion with CD20 Antibodies as New Approach in the Treatment of Inflammatory and Immunological Events Associated with Spinal Cord Injury

et al. 2016

Self Cite

View full text Add to dashboard Cite

Spinal cord injury (SCI) is a highly debilitating pathology that has irreversible impacts and results in functional loss. We evaluated the anti-inflammatory and immunologic role of antibody-mediated depletion of B cells through the glycoengineered anti-muCD20 antibody (18B12) in an experimental model of spinal cord compression, in vivo and ex vivo. Intraperitoneal 18B12 was administered at a dose of 30 mg/kg, 1 h and 6 h after SCI, and mice were sacrificed 24 h after trauma. We demonstrated, in vivo, that 18B12 slowed severe hindlimb motor dysfunction (Basso Mouse Scale score) and neuronal death by histological evaluation in SCI mice, as well as decreased expression of nuclear factor-kB, inducible nitric oxide synthase, cytokines, and glial fibrillary acidic protein. Also, 18B12 reduced expression of microglia, just as it lowered the expression of B and T lymphocytes. Moreover, in spinal cord organotypic cultures, pretreatment with 18B12 significantly reduced nitric oxide expression and protected cells from cell death [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay]. In this study, we showed that 18B12 treatment reduces the development of inflammation and tissue injury by alteration of the immune system associated with SCI. This study increases the current knowledge that B-cell depletion is able to exert immunomodulating actions in damaged spinal cords.

show abstract

Section: Discussionmentioning

confidence: 99%

B-Cell Depletion with CD20 Antibodies as New Approach in the Treatment of Inflammatory and Immunological Events Associated with Spinal Cord Injury

et al. 2016

Self Cite

View full text Add to dashboard Cite

show abstract

“…47,48 Reactive oxygen species (ROS) that can induce DNA damage and accelerate cellular senescence are upregulated in the damaged neural tissue after SCI. [49][50][51][52] Recent studies revealed that an inhibition of mTOR decelerates cellular senescence and increases the lifespan in diverse organisms. [53][54][55] mTOR is involved in agerelated diseases, such as atherosclerosis, metabolic syndrome, osteoporosis, neurodegeneration and macular degeneration.…”

Section: Suppression Of Cellular Senescence and Organismalmentioning

confidence: 99%

The role of mTOR signaling pathway in spinal cord injury

et al. 2012

View full text Add to dashboard Cite

T he mammalian target of rapamycin (mTOR) signaling pathway plays an important role in multiple cellular functions, such as cell metabolism, proliferation and survival. Many previous studies have shown that mTOR regulates both neuroprotective and neuroregenerative functions in trauma and various diseases in the central nervous system (CNS). Recently, we reported that inhibition of mTOR using rapamycin reduces neural tissue damage and locomotor impairment after spinal cord injury (SCI) in mice. Our results demonstrated that the administration of rapamycin at four hours after injury significantly increases the activity of autophagy and reduces neuronal loss and cell death in the injured spinal cord. Furthermore, rapamycintreated mice show significantly better locomotor function in the hindlimbs following SCI than vehicle-treated mice. These findings indicate that the inhibition of mTOR signaling using rapamycin during the acute phase of SCI produces neuroprotective effects and reduces secondary damage at lesion sites. However, the role of mTOR signaling in injured spinal cords has not yet been fully elucidated. Various functions are regulated by mTOR signaling in the CNS, and multiple pathophysiological processes occur following SCI. Here, we discuss several unresolved issues and review the evidence from related articles regarding the role and mechanisms of the mTOR signaling pathway in neuroprotection and neuroregeneration after SCI.

show abstract

“…Дослідження патогенетичних механізмів травми різного генезу свідчать про те, що клітинна й тканинна гіпоксія призводить до дисбалансу окиснювально-відновних про-цесів, мітохондріальної дисфункції, вивільнення прозапальних цитокінів, чинників клітинної ад-гезії, а це, у свою чергу, значно збільшує про-дукцію вільних радикалів [2]. Основними джере лами вільних радикалів є мітохондрії, ксантинок сидази, NAD(P)H-оксидази, а також велика кількість ендотеліальних факторів [3,4]. Дослі-дження показують, що оксидативний стрес у пацієнтів з різними видами травм розвивається практично відразу після початкового ушкоджен ня, переходячи з макроскопічного рівня на клітинний і молекулярний [5].…”

unclassified

The ways of free radical oxidation correction in the early posttraumatic period after the combined trauma of the chest and hips

Khudobyak¹

2016

MCCh

View full text Add to dashboard Cite

The article adduces the results of the research performance of reactive oxygen in the blood and liver tissue of rats in early post-traumatic period after combined chest trauma and hips. It was established that the post-traumatic period after combined chest trauma and both hips characterizing by increasing of free oxygen radicals percentage in the blood leukocyte suspensions and liver tissue after 1 day with advanced dynamics within 3 days of the experiment. It was showed the effectiveness of the emoxipin and mexicor use in animals with combined trauma within 1 day of post-traumatic period. Comparing the data in groups of correction antihypoxants with metabolic action revealed more expressed effect of the mexicor within 3 days of the experiment, which due to the presence of succinic acid in its composition.

show abstract

Nitric oxide in the injured spinal cord: Synthases cross-talk, oxidative stress and inflammation

Cited by 135 publications

References 108 publications

B-Cell Depletion with CD20 Antibodies as New Approach in the Treatment of Inflammatory and Immunological Events Associated with Spinal Cord Injury

B-Cell Depletion with CD20 Antibodies as New Approach in the Treatment of Inflammatory and Immunological Events Associated with Spinal Cord Injury

The role of mTOR signaling pathway in spinal cord injury

The ways of free radical oxidation correction in the early posttraumatic period after the combined trauma of the chest and hips

Contact Info

Product

Resources

About