THE EFFECT OF GABA-BENZODIAZEPINE RECEPTOR COMPLEX MODULATORS (MPTD-01 AND BS 34-20) ON THE CEREBRAL CORTEX AFTER EXPERIMENTAL BRAIN INJURY

Abstract

Background. Traumatic brain injury (TBI) is a major medical, social, and public health problem, In the military population the TBI incidence also remains high due to blunt head trauma and blast injuries. Considering the substantial TBI burden on society, including possible postraumatic epilepsy onset and other comorbidities the search for new treatment methods, including drug design with the identification of new molecules, is highly relevant. Aim: The study aimed to evaluate the effect of GABA-benzodiazepine receptor complex modulators (hydrogenated 2,3-benzodiazepines MPTD-01 та BS 34-20) on rat cerebral cortex after traumatic brain injury Materials and methods. The experiment was carried out on male Wistar rats. To obtain traumatic brain injury we used the weight drop model. Based on the received treatment, the Rats were divided into intact, placebo (II), and MPTD-01 (III) and BS 34-20 (IV) groups. The cerebral cortex in the impact zone was harvested for examination. The light microscopy was performed on 3, 7, 14, and 21 days after injury. Results. The observed histological picture of the changes in the cerebral cortex, especially in the II group is similar to those, described by other research papers as mild- to severe traumatic brain injury. The reproduction of the blunt trauma model leads to a series of typical changes that replace each other and can be characterized as alteration, edema, phase of cellular reactions, and repair. Unlike the placebo group, the III and IV experimental groups (GABA-benzodiazepine receptor complex modulators administration) cerebral cortex 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 was observed on the 21st day of the experiment. Conclusion. Such morphological changes can be considered a neuroprotective effect, however, to fully characterize the effects of the GABA-benzodiazepine receptor complex modulators, glial reactions and neuron-glial interactions should be investigated.