Inhibition of the nuclear factor—κB activation with pyrrolidine dithiocarbamate attenuating inflammation and oxidative stress after experimental spinal cord trauma in rats

Rosa, G. La; Cardali, Salvatore; Genovese, Tiziana; Conti, Alfredo; Paola, Rosanna Di; Torre, Domenico La; Cacciola, Fabio; Cuzzocrea, Salvatore

doi:10.3171/spi.2004.1.3.0311

Cited by 64 publications

(61 citation statements)

References 72 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…To analyze the molecular mechanisms responsible for GILZ anti-inflammatory activity, we evaluated the classical NF-κB pathway [33,34] measured by Western blot IκB-α levels and nuclear translocation of NF-κB (NF-κB p65) twenty-four hours after SCI induction. A basal level of IκB-α was detected in the spinal cord from both WT and GILZ TG sham-operated animals (Fig.…”

Section: Gilz Over-expression Reduces Inos Nitrotyrosine and The Damentioning

confidence: 99%

Glucocorticoid-Induced Leucine Zipper (GILZ) Over-Expression in T Lymphocytes Inhibits Inflammation and Tissue Damage in Spinal Cord Injury

et al. 2012

Self Cite

View full text Add to dashboard Cite

Spinal cord injury (SCI) is a traumatic event that causes a secondary and extended inflammation characterized by infiltration of immune cells, including T lymphocytes, release of pro-inflammatory mediators in the lesion site, and tissue degeneration. Current therapeutic approaches for SCI are limited to glucocorticoids (GC) due to their potent antiinflammatory activity. GC efficacy resides, in part, in the capability to inhibit NF-κB, T lymphocyte activation, and the consequent cytokine production. In this study, we performed experiments aimed to test the susceptibility of glucocorticoidinduced leucine zipper (GILZ) transgenic (GILZ TG ) mice, in which GILZ is selectively over-expressed in T lymphocytes, to SCI induction. Consistent with a decreased inflammatory response, GILZ TG were less susceptible to SCI as compared to wild-type littermates. Notably, inhibition of NF-κB activation and nuclear translocation, diminished T lymphocytes activation and tissue infiltration, as well as decreased release of cytokines were evident in GILZ TG as compared to wild-type mice. Moreover, GILZ TG showed a reduced tumor necrosis factor-α, IL-1β, Inductible nitric oxide synthase (iNOS) and nytrotyrosine production, apoptosis, and neuronal tissue damage. Together these results indicate that GILZ mimics the anti-inflammatory effect of GC and represents a potential pharmacological target for modulation of T lymphocyte-mediated immune response in inflammatory disorders, such as SCI.

show abstract

Section: Gilz Over-expression Reduces Inos Nitrotyrosine and The Damentioning

confidence: 99%

Glucocorticoid-Induced Leucine Zipper (GILZ) Over-Expression in T Lymphocytes Inhibits Inflammation and Tissue Damage in Spinal Cord Injury

et al. 2012

Self Cite

View full text Add to dashboard Cite

show abstract

“…Hamada et al [13] reported that intravenous injection of an iNOS inhibitor, N G -nitro-L-arginine methyl ester, reduces motor dysfunction in SCI models. La Rosa and colleagues [22] also reported that administration of pyrolidine dithiocarbamate (PDTC), which inhibits the activation of NF-jB and thus reduces iNOS expression, significantly improves motor function. These experimental results suggest that a NOS blocker and PDTC are candidate future pharmacologic treatments for SCI in humans.…”

Section: Limitations and Problems In The Present Studymentioning

confidence: 99%

Significant correlation between cerebrospinal fluid nitric oxide concentrations and neurologic prognosis in incomplete cervical cord injury

et al. 2007

View full text Add to dashboard Cite

In animal models of spinal cord injury (SCI), inducible NO (nitric oxide) synthase is expressed in the spinal cord immediately after sustaining SCI. Excessive NO production has cytotoxic effects and induces neuronal apoptosis, causing neural degeneration and neurodysfunction in the spinal cord. Little is known, however, about the relationship between NO x (NO metabolites: nitrite and nitrate) levels in the cerebrospinal fluid (CSF) and neurologic severity or recovery in clinical cases. The objective of the present study was to examine the correlation between CSF NO x levels and neurologic severity or recovery in SCI. Twenty-five patients with incomplete cervical cord injury (CCI) were examined. Eight cases were treated conservatively (non-operated group). Seventeen cases underwent surgical intervention (operated group). NO x levels in the CSF were measured using the Griess method. The severity of the neurologic impairment was assessed using Frankel's classification and the American Spinal Injury Association motor score (ASIA MS). The degree of neurologic recovery was assessed using Frankel's classification and the ASIA motor recovery percentage (MRP). There was no significant difference in the NO x levels between the CCI group (NO x levels: 5.9 ± 0.7 lM) and the 36 control subjects (1 volunteer and 35 patients without neurologic disorders, NO x levels: 4.9 ± 0.3 lM). There was no significant difference in NO x levels and MRP between the non-operated group and the operated group. The NO x levels in total SCI group were significantly correlated with the ASIA MS and MRP. There was a significant correlation between CSF NO x levels and neurologic severity or recovery in incomplete CCI.

show abstract

“…It was reported that PDTC could protect against brain ischemia (Nurmi et al, 2004b) and spinal cord trauma (La Rosa et al, 2004). However, to date, no study has been conducted to investigate the influence of PDTC on cerebral vasospasm.…”

Section: Introductionmentioning

confidence: 99%

Potential Contribution of Nuclear Factor-κB to Cerebral Vasospasm after Experimental Subarachnoid Hemorrhage in Rabbits

Zhou

Shi

Hang

et al. 2007

J Cereb Blood Flow Metab

View full text Add to dashboard Cite

Nuclear factor-jB (NF-jB) plays a key role in inflammation, which is involved in the development of cerebral vasospasm after subarachnoid hemorrhage (SAH). In the present study, we assessed the potential role of NF-jB in regulation of cerebral vasospasm. Nuclear factor-jB DNA-binding activity was measured in cultured vascular smooth muscle cells (VSMCs) treated with hemolysate and pyrrolidine dithiocarbamate (PDTC, 80 lmol/L), an inhibitor of NF-jB. Forty-two rabbits were divided into three groups: control, SAH, and PDTC groups (n = 14 for each group). The caliber of the basilar artery was evaluated. Nuclear factor-jB DNA-binding activity and the gene expression levels of cytokines and adhesion molecules in the basilar artery were measured. Immunohistochemical study was performed to assess the expression and localization of tumor necrosis factor (TNF)-a, intercellular adhesion molecule (ICAM)-1, and myeloperoxidase (MPO). It was observed that NF-jB DNA-binding activity was significantly increased by treatment with hemolysate in cultured VSCMs, but this increase was suppressed by pretreatment with PDTC. Severe vasospasm was observed in the SAH group, which was attenuated in the PDTC group. Subarachnoid hemorrhage could induce increases of NF-jB DNA-binding activity and the gene expression levels of TNF-a, interleukin (IL)-1b, ICAM-1, and vascular cell adhesion molecule (VCAM)-1, which were reduced in the PDTC group. Immunohistochemical study demonstrated that the expression levels of TNF-a, ICAM-1, and MPO were all increased in the SAH group, but these increases were attenuated in the PDTC group. Our results suggest that NF-jB is activated in the arterial wall after SAH, which potentially leads to vasospasm development through induction of inflammatory response.

show abstract

Inhibition of the nuclear factor—κB activation with pyrrolidine dithiocarbamate attenuating inflammation and oxidative stress after experimental spinal cord trauma in rats

Cited by 64 publications

References 72 publications

Glucocorticoid-Induced Leucine Zipper (GILZ) Over-Expression in T Lymphocytes Inhibits Inflammation and Tissue Damage in Spinal Cord Injury

Glucocorticoid-Induced Leucine Zipper (GILZ) Over-Expression in T Lymphocytes Inhibits Inflammation and Tissue Damage in Spinal Cord Injury

Significant correlation between cerebrospinal fluid nitric oxide concentrations and neurologic prognosis in incomplete cervical cord injury

Potential Contribution of Nuclear Factor-κB to Cerebral Vasospasm after Experimental Subarachnoid Hemorrhage in Rabbits

Contact Info

Product

Resources

About