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A Neurosphere Assay to Evaluate Endogenous Neural Stem Cell Activation in a Mouse Model of Minimal Spinal Cord Injury
Published on: September 13, 2018
Early effects of modulating nuclear factor-kappaB activation on traumatic spinal cord injury in rats
Octavio Jiménez-Garza1, Javier Camacho, Antonio Ibarra
1Pharmacology Section, CINVESTAV-IPN, México City, México.
Abstract:
Genes regulated by NF-kappaB play an important role on secondary damage and repair after spinal cord injury (SCI). To assess the early effects of the pharmacological inhibition and overactivation of NF-kappaB, pyrrolidine dithiocarbamate (PDTC) or lipopolysaccharide were given to rats before or after SC contusion. The amount of spared SC tissue was higher (P < 0.05) at 24 h postinjury in rats post-treated with PDTC; both PDTC-treated rats showed no significant trend to decrease polymorphonuclear infiltrate. p65 subunit was present in inflammatory cells, neurons, and astrocytes at the injury site. These data support further investigation on functional effects of NF-kappaB inhibition in acute SCI.
Insights
Pharmacological inhibition of nuclear factor-kappa B (NF-kappaB) using PDTC after spinal cord injury (SCI) increased spared tissue. NF-kappaB inhibition shows promise for acute SCI treatment.
Area of Science:
- Neuroscience
- Immunology
- Pharmacology
Background:
- Nuclear factor-kappa B (NF-kappaB) pathway is implicated in secondary damage and repair processes following spinal cord injury (SCI).
- Understanding the early effects of modulating NF-kappaB activity is crucial for developing therapeutic strategies for acute SCI.
Purpose of the Study:
- To investigate the early effects of pharmacological inhibition and overactivation of NF-kappaB on spinal cord tissue sparing and inflammation after contusion injury.
- To assess the cellular localization of the p65 subunit of NF-kappaB at the injury site.
Main Methods:
- Rats underwent spinal cord contusion injury.
- Rats received either pyrrolidine dithiocarbamate (PDTC) for NF-kappaB inhibition or lipopolysaccharide for NF-kappaB activation, administered before or after injury.
- Spared spinal cord tissue was quantified at 24 hours post-injury.
- Polymorphonuclear cell infiltration was assessed.
- Immunohistochemistry was used to detect the p65 subunit of NF-kappaB in inflammatory cells, neurons, and astrocytes.
Main Results:
- Post-treatment with PDTC significantly increased the amount of spared spinal cord tissue at 24 hours post-injury (P < 0.05).
- PDTC treatment did not show a significant trend in decreasing polymorphonuclear cell infiltrate.
- The p65 subunit of NF-kappaB was detected in inflammatory cells, neurons, and astrocytes within the injury site.
Conclusions:
- Pharmacological inhibition of NF-kappaB with PDTC demonstrates a neuroprotective effect by increasing spared tissue in the acute phase of SCI.
- While NF-kappaB inhibition shows potential, its effect on reducing inflammatory cell infiltration requires further investigation.
- The presence of NF-kappaB subunits in various cell types at the injury site highlights its complex role in SCI pathophysiology.
- These findings warrant further research into the functional outcomes of NF-kappaB inhibition in acute SCI.
