Rat hippocampus structures after experimental traumatic brain injury and GABA-benzodiazepine receptor complex modulators administration

the global incidence of traumatic brain injury remains high and long-lasting consequences of such injury brings both medical and social burden on public health. Such comorbidity among others includes early and late post-traumatic epilepsy, post-traumatic stress disorder and depression and anxiety, cognitive impairments often require prolonged treatment. The incidence of such negative outcomes of traumatic brain injury is extremely high among deployed military personnel and war-affected civilians. All of the facts that mentioned above require the development of new strategies, including novel drug designing to provide complex treatment and overcome existing difficulties in rehabilitation after traumatic brain injury. The aim of the study was to evaluate the effect of GABA-benzodiazepine receptor complex modulators on rat hippocampus zones after traumatic brain injury. The experiment was carried out on male Wistar rats. To obtain traumatic brain injury we used a modified weight drop model. Rats were divided to intact, placebo (received placebo treatment), MPTD-01 (treated with 4-(4’-Methoxyphenyl)-2,3,4,5-tetrahydro-1H-2,3-benzodiazepin-1-one; intraperitoneally, 5 mg/kg once a day) and BS 34-20 (treated with 6-(4-Methoxyphenyl)-7H-[1,2,4]triazolo[3,4-a][2,3]benzodiazepine; intraperitoneally, 5 mg/kg once a day) groups. The light microscopy with hematoxylin and eosin straining was performed on 3, 7, 14, 21 days after injury. Hippocampus CA1, CA3 zones and dentate gyrus were studied. Unlike the placebo group, the MPTD-01 and BS 34-20 experimental groups demonstrated a smoothing of the swelling phase and its reduction, a shift in the time phase of cellular reactions to a later time. In the BS 34-20 group, minimal edema and more complete restoration of the structure of the hippocampus was observed on the 21st day of the experiment. Even though the studied structures of the hippocampus were not directly traumatized during the performance of the TBI model, they also undergo remodeling according to the revealed patterns. Such remodeling consists in the sequential change of the swelling phase by the phase of cellular reactions followed by the recovery phase. As it was shown in current study, the use of MPTD-01 and BS 34-20 in rats after a moderate traumatic brain injury leads to a time shift and smoothing of the edema phase. The possible explanation of the studied drugs action is excitotoxicity reduction what results in less pronounced secondary alteration. Tested novel hydrogenated benzodiazepines can be considered as promising drugs for neurodegeneration prevention after mild traumatic brain injuries, but their effect on glia activation and other phases of inflammatory cascade both with neuron and gliocyte ultrastructure still need to be investigated.