Introduction. The search for and development of new drugs capable of reducing the severity of neurological deficit in traumatic brain injury are a critical task for investigational pharmacology. Chromone-containing allylmorpholines are a new group of neuroprotective drug candidates that have been shown to inhibit acetylcholinesterase and butyrylcholinesterase, and block N-methyl-D-aspartate receptors in vitro.Aim. This study aimed to evaluate the neuroprotective activity of the allylmorpholine derivative (E)-4-[3-(8-bromo-6-methyl-4-oxo-4H-chromen- 3-yl)-1-cyclohexylallyl]morpholin-4-ium chloride (33b) in vivo using a rat model of traumatic brain injury.Materials and methods. Traumatic brain injury was induced using the controlled cortical impact model. The allylmorpholine derivative was administered intraperitoneally at 1, 10, or 50 mg × kg-1 b.w. at 1 h after trauma induction, and then daily for the next 6 d. The neurological deficit was assessed using the Limb Placing, Open Field, Elevated Plus Maze, Beam Walking, and Cylinder tests.Results and discussion. At all doses administered, the allylmorpholine derivative had no positive effect on the motor function or exploratory behavior following traumatic brain injury. In the Elevated Plus Maze, 10 mg × kg-1 b.w. of the compound further suppressed exploratory behaviour in the injured animals, which appears to be consistent with its sedative properties observed previously in zebrafish.Conclusion. Despite the previously described in vitro affinity of allylmorpholines towards several molecular targets crucial for the pathogenesis of brain trauma and posttraumatic functional recovery, an allylmorpholine derivative had no neuroprotective effect in a rat model of traumatic brain injury in this study. These results further emphasize the importance of in vivo evaluation of potential neuroprotective drug candidates.
Objectives. Ischemic stroke is a leading cause of death and disability worldwide. To search for new therapeutic and pharmacotherapeutic strategies, numerous models of this disease have been proposed, the most popular being transient middle cerebral artery occlusion. Behavioral and sensorimotor testing, biochemical, and histological methods are traditionally used in conjunction with this model to assess the effectiveness of potential treatment options. Despite its wide overall popularity, electroencephalography/electrocorticography is quite rarely used in such studies. Materials and methods. In the present work, we explored the changes in brain electrical activity at days 3 and 7 after 30- and 45-min of transient middle cerebral artery occlusion in rats. Results. Cerebral ischemia altered the amplitude and spectral electrocorticogram characteristics, and led to a reorganization of inter- and intrahemispheric functional connections. Ischemia duration affected the severity as well as the nature of the observed changes. Conclusions. The dynamics of changes in brain electrical activity may indicate a spontaneous partial recovery of impaired cerebral functions at post-surgery day 7. Our results suggest that electrocorticography can be used successfully to assess the functional status of the brain following ischemic stroke in rats as well as to investigate the dynamics of functional recovery.
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