CHANGES IN BEHAVIOURAL REACTIONS OF RATS FOLLOWING MODELLED TRAUMATIC BRAIN INJURY AND THEIR CORRECTION WITH TRANSCRIPTION FACTORS MODULATORS

Abstract

This study aimed at investigating the effect of modulators of transcription factors NF-κB, AP-1 and Nrf2 on the behavioural responses of rats in the "Dark-light chamber" and "Open field" tests following the simulation of traumatic brain injury (TBI). The study included 42 white Wistar male rats weighing 180-220 g, divided into 6 groups of 7 rats in each: the control group included the animals exposed to the above mentioned tests before TBI modelling and 3 – 7 days after it; as for the animals of other groups, for 7 days after TBI simulation they were given intraperitoneal injections of the following transcription factor modulators: ammonium pyrrolidine dithiocarbamate, an inhibitor of nuclear translocation NF-κB, was injected in a dose of 76 mg/kg; AP-1 SR 11302 inhibitor given in a dose of 1 mg/kg; Nrf2 inductors as dimethyl fumarate given in a dose of 15 mg/kg of a 10% dimethyl sulfoxide solution and epigallocatechin-3-gallate in a dose of 1 mg/kg as well as a water-soluble form of quercetin (corvitin), which acts as an NF-κB inhibitor and Nr inducer, in a dose of 100 mg / kg (10 mg / kg in terms of quercetin). Unlike the test animals, the rats of the control group were given intraperitoneal injections of 1 ml of isotonic sodium chloride solution. It has been found out that during the first week following TBI simulation, the locomotor activity and psycho-emotional state of the rats were disturbed: the indicators of motor and exploratory activity, orienting reaction became deteriorated, anxiety and fear increased as well as the frequency of self-grooming actions. The use of inhibitors of transcription factors NF-κB (ammonium pyrolidindithiocarbamate) and AP-1 (SR 11302), Nrf2 inducers (dimethyl fumarate and epigallocatechin-3-gallate) and the water-soluble form of quercetin (corvitin) for the 1st week after TBI simulation improves motor performance and exploratory activity, orienting reaction, and reduces emotional anxiety and fear as well.