Abstract
Spinal cord injury (SCI) main cause of motor dysfunction results in loss of feelings partially or completely. The current study investigated indirubin-3′-oxime (IR3O) for treatment of SCI in rat model and evaluated the related mechanism. Rats in model SCI and ID30 groups were subjected to laminectomy at 8th thoracic vertebra level. Vertebral column was secured by clamping T6 and T10 and SCI model was established by dripping a hammer. Treatment groups received 0.25, 0.5, 0.75 and 1.0 mg/kg doses of ID30 daily for 2-weeks post-surgery. Treatment with ID30 effectively improved BBB score in rats with SCI in dose-based manner. Accumulation of water in spinal cord tissues was alleviated significantly on treatment of SCI rats with ID30. ID30 treatment significantly alleviated SCI mediated higher serum levels of TNF-α and cytokines (IL-1β and IL-6) in SCI rats. In ID30 treated SCI rats SOD, CAT and GSH activities were significantly alleviated. The SCI mediated increased cleaved caspase-3 and -9 levels were alleviated by ID30 treatment significantly. Moreover, ID30 treatment suppressed SCI mediated elevation of PGE2, COX‑2 levels and significantly (P<0.05) elevated PPAR-γ expression. The ID30 treatment of SCI rats significantly (P<0.05) elevated PI3K and Akt phosphorylation. Thus, ID30 inhibited edema and improved BBB score in rats with SCI by targeting pro-inflammatory cytokines and oxidative response. Moreover, in SCI rats ID30 treatment down-regulated apoptotic proteins, promoted PPAR-γ activation and elevated PI3K/Akt phosphorylation. Thus, ID30 has potential to be studied further for development of therapeutic strategy for SCI.
Clinic serum levels of Plin5 is therapeutic target of spinal cord injury and Plin5 reduced inflammation in spinal cord injury via silent information regulator 1 dependent inhibition of NLRP3 inflammasome
