Agmatine inhibits nuclear factor-jB nuclear translocation in acute spinal cord compression injury rat model

Abstract

Secondary damage after acute spinal cord compression injury (SCCI) exacerbates initial insult. Nuclear factor kappa-B  (NF-jB)-p65 activation is involved in SCCI deleterious effects. Agmatine (Agm) showed neuroprotection against various CNS injuries. However, Agm impact on NF-jB signaling in acute SCCI remains to be investigated. The present study compared the effectiveness of Agm therapy and decompression laminectomy (DL) in functional recovery, oxidative stress,  inflammatory and apoptotic responses, and modulation of NF-jB activation in acute SCCI rat model. Rats were either sham-operated or subjected to SCCI at T8–9, using 2-Fr. catheter. SCCI rats were randomly treated with DL at T8–9,  intraperitoneal Agm (100 mg/kg/day), combined (DL/Agm) treatment or saline (n= 16/group). After 28-days of neurological follow-up, spinal cords were either  subjected to biochemical measurement of oxidative stress and inflammatory markers or histopathology and immuno-histochemistry for NF-jB-p65 and  caspase-3 expression (n= 8/group). Agm was comparable to DL in facilitating neurological functions recovery, reducing inflammation (TNF-a/interleukin-6), and apoptosis. Agm was distinctive in combating oxidative stress. Agm neuroprotective effects were paralleled with inhibition of NF-jB-p65 nuclear translocation. Combined pharmacological and surgical interventions were proved superior in functional recovery. In conclusion, present research suggested a new mechanism for Agm neuroprotection in rats SCCI through inhibition of NF-jB activation.

Keywords: Spinal cord injury; Agmatine; Nuclear factor kappa B; Oxidative stress; Inflammation; Apoptosis