Investigation the effects of memantine and melatonin treatment after traumatic brain injury in rats

Brain injury following head trauma occurs after complex pathophysiological processes including activation of N-methyl-D-aspartate (NMDA) receptor, disruption of intracellular calcium (Ca+2) homeostasis and oxidative stress. Extrasynaptic NMDA receptor inhibitor, memantin, and free radical scavenger, melatonin, have fewer side effects and are used in humans in treatment of neurodegenerative disorders. In this study, the effects of memantin and melatonin on traumatic brain injury was investigated in male Sprague-Dawley rats. Brain trauma was generated by dropping a 10 grams of metallic cylinder from 50 cm height, directly onto the brain over a hole with 6 mm diameter on the skull, under rompun and ketasol anesthesia. Immediately after trauma memantin, melatonin and memantin/melatonin combination were applied to rats. At the end of behavioral examination, injury volume 24 hours later than trauma and apoptotic cell death were determined. At the end of the study, although it was identified that memantin- and melatonin-only treatments also reduced brain damage, reduction in brain damage was more significant in rats treated with this combination treatment. In evaluation of apoptosis with TUNEL staining, damage was determined to be lower in all three of the treatments, however it was determined that this reduction was significant in memantin/melatonin combination as compared to control as well as other treatment groups. Open field examination was in compliance with the infarct area. In addition to better motor coordination, less depressive behaviour and better movement was identified in treatment groups compared to control. Consequently, since memantin and melatonin individually affect different pathological processes after brain trauma, the observation that injury and apoptotic cell death were reduced in rats treated with memantin and melatonin combination, lead to the use of this combination in clinical studies.