Investigation of possible protective effects of combination of uridine and therapeutic hypothermia in experimental traumatic brain injury

Traumatic brain injury is accepted as an emergency situation with high morbidity and mortality rates worldwide. Although most of the patients admitted to the hospital are diagnosed with mild traumatic brain injury, permanent damage could be seen in the long term period. The physiopathological processes of traumatic brain injury are classified as; primary injury and secondary injury period. While primary brain injury occurs immediately after trauma, secondary injury occurs hours and days after primary injury. The aim of this study is to examine the changes in oxidative, inflammatory and apoptotic parameters within the secondary injury period in an experimental model of traumatic brain injury and to investigate the neuroprotective effect of Uridine and/or hypothermia combination therapy. In our study, the free weight drop model defined by Marmarou et al. was used and mild hypothermia (32-34.0±1°C) was applied for 4 hours. Uridine was administered intraperitoneally in 500mg/kg dose for 7 days following traumatic brain injury. Subsequently, brain tissue analyzes were performed using TTC, Western Blot and ELISA kits. Among the oxidative parameters, Glutathione Peroxidase was increased with the combination therapy, while Catalase and Myeloperoxidase were decreased. Interleukin-1β and Interleukin-6, which are accepted as inflammatory markers, decreased with combination therapy. Poly ADP-ribose polymerase-1, which is involved in the necrotic process, was increased after TBI and decreased with hypothermia, uridine and combination therapy. The main goal in the approach to traumatic brain injury is to protect the patient against the effects that occur during the secondary injury period. In our study, the efficacy of Uridine-hypothermia combination therapy was demonstrated after seven days of treatment, which is the first in the literature in this respect. With other studies to be conducted in this area, it is aimed to be a treatment approach that can be used in routine practice in mild traumatic brain injury and to be included in trauma patient management guidelines.