The evaluation of the effect of the use of acute single dose mk-801 on administrative document and cognitive behavior after the experimental head trauma model applied in immathy rats

The aim of this study was to investigate the long-term effects of head trauma on immature rats and the long-term neuroprotective effect of acute single-dose MK-801 after trauma. In the study, immature rats were followed by intraperitoneal 1 mg/kg MK-801 after trauma and followed by weekly body weight measurements for 16 weeks and at the end of the 16th week Open Field and Morris Water Labyrinth Tests were applied. After behavioral tests, rats were sacrified and brain tissues were removed. Morphological evaluation was performed by obtaining neuron counts in bilateral hippocampal CA1, CA3 and DG areas in brain tissues obtained. In addition, some of the brain tissues of rats are histologically detected as nerve growth factor (NGF), brain derived neurotrophic factor (BDNF), N-Methyl-D-Aspartic acid receptor (NMDA-R) and glial fibrillar acidic protein (GFAP) immunohistochemical staining and distribution in hippocampus tissue were investigated. NGF, BDNF and NMDA-R protein levels in the hippocampus tissue homogenate were investigated by ELISA (Enzyme-Linked ImmunoSorbent Assay) and the effects of MK-801 on the brain hippocampus region were evaluated. According to the findings obtained from the study; there was no statistically significant difference between the groups in terms of weight gain / decrease in rats (p> 0.05). According to the findings of the hippocampal neuron count, it was determined that the number of neurons in the CA1, CA3 and DG areas of the bilateral hippocampus in the trauma + MK-801 group were maintained and were close to the control group. According to immunohistochemical findings, the trauma was found to significantly decrease BDNF, NGF and NMDA-R expression in the CA1, CA3 and DG areas of the bilateral hippocampus, while the use of MK-801 increased the reversal of BDNF, NGF and NMDA-R expression. In addition, it was observed that MK-801 significantly increased GFAP expression in hippocampal areas. Similar to the histological findings, ELISA findings showed a statistically significant decrease in NGF, BDNF and NMDA-R protein levels in the right hippocampus in the trauma group compared to the control group (p = 0.026, p = 0.017 and p = 0.001, respectively). There was a statistically significant increase in trauma + MK-801 group compared to trauma group (p = 0.035, p = 0.030 and p = 0.001, respectively). According to the open-field test results, it was determined that the time spent in the middle area of the trauma + MK-801 group was highest and the time spent in the periphery was the lowest. In addition, trauma + MK-801 group had the highest distance and movement speed. According to Morris water maze findings, trauma + MK-801 group was found to be shorter than the trauma group. There was no significant difference between the groups at the end of day 4 in terms of swimming speed (p> 0.05). It was determined that the time spent in the target quadrant of the trauma + MK-801 group was longer compared to the trauma group, and that the time spent in the target quadrant of the trauma group was statistically significantly shorter than the control group. As a result, it has been shown that traumatic brain injury negatively affects learning and memory. Keywords: Traumatic brain injury, immature rats, memory, learning, MK-801, ELISA, BDNF, NGF, NMDA-R, GFAP.