Repositioning of an Anti-depressant Drug, Agomelatine as Therapy for Brain Injury Induced by Craniotomy

Abstract

Traumatic brain injury (TBI) leads to the disruption of blood-brain barrier integrity and therefore results in increased brain water content (brain edema). Brain edema is a significant factor for increased intracranial pressure (ICP), which ultimately causes functional disability and death. The decompressive craniotomy (DC) is a surgical procedure widely used for treating increased ICP following TBI. The life-saving craniotomy itself results in brain injury. The objective of this study is to investigate the effect of agomelatine against craniotomy induced brain injury. The craniotomy was performed by a variable speed micro-motor dental driller of 0.8 mm drill bit. The present study, in addition to blood-brain permeability, brain water content (edema) and histological examination of the brain, also estimated locomotor activity, oxidant, and antioxidant parameters. Results show that the craniotomy induced increase in the blood-brain barrier permeability, brain water content (edema), oxidative stress (lipid peroxide and nitric oxide) and impaired antioxidant mechanisms (superoxide dismutase, catalase, and reduced glutathione) in rats. The craniotomy was also found to increase neuronal cell death indicated by augmented chromatolysis and impaired locomotor activity. Administration of agomelatine after the craniotomy ameliorated histopathological, neurochemical and behavioural consequences of craniotomy. Thus agomelatine is effective against brain injury caused by craniotomy.