Effects of Modulators of Redox-Sensitive Transcription Factors on Neurologic Deficit in Rats After Traumatic Brain Injury

Abstract

<jats:p>This study was aimed as investigating the effects of modulators of transcription factors NF-κB, AP-1 and Nrf2 on the survival rate of white rats and the development of neurological deficits following the simulation of traumatic brain injury (TBI). The study included 110 white Wistar male rats weighing 180-220 g, divided into 6 groups. Control group involved animals after the TBI injury simulation (n=30). The animals of other groups (16 rats in each) were intraperitoneally injected with modulators of transcription factors after the simulation of the trauma for 7 days: ammonium pyrrolidine dithiocarbamate, an inhibitor of nuclear translocation NF-κB, was injected in a dose of 76 mg/kg; AP-1 SR 11302 inhibitor – in a dose of 1 mg/kg; Nrf2-ARE system inductors as dimethyl fumarate in a dose of 15 mg/kg in a 10% dimethyl sulfoxide solution and epigallocatechin-3-gallate in a dose of 1 mg/kg. The test animals were also injected with a water-soluble form of quercetin (corvitin), which acts as an NF-κB inhibitor and Nrf2 inducer, in a dose of 100 mg/kg (10 mg/kg in terms of quercetin). The animals in the control group were injected intraperitoneally with 1 ml of isotonic sodium chloride solution instead of the tested compounds mentioned above. It has been found out that on the 7th day after the simulation of moderate TBI most animals showed signs of neurological deficit including impaired muscle tone (83.3%), impaired coordination (83.3%) and pain reaction (66.7%). Integral indicator of neurological deficit by Todd et al. 100-score grading scale was 51.33±2.95. The use of inhibitors of transcription factors NF-κB (ammonium pyrrolidinedithiocarbamate) and AP-1 (SR 11302), the Nrf2-ARE system inducers (dimethylfumarate and epigallocatechin-3-gallate) and the water-soluble form of quercetin (corvitin) increases rats’ survival rate, significantly limits their signs of neurological deficit and its integral index.</jats:p>