Study of the neuroprotective activity of mafedine, an alpha-2 adrenergic receptor agonist, by modeling a traumatic brain injury in rats

In this study, the neuroprotective activity of alpha-2 adrenergic receptor agonist (6-oxo-1-phenyl-2- (phenylamino)-1,6-dihydropyrimidine-4-sodium olate) (mafedine) at the doses of 2.5 and 5 mg/kg was estimated by modelling a traumatic brain injury in rats. The effect of mafedine on rat behaviour and their motor activity was also assessed following such conventional tests as limb placing, open field, elevated plus maze, cylinder, beam walking and staircase. A morphological analysis of the amount of brain damage in the experimental animals was carried out on the 7th day following injury. In addition, the protein composition of the cerebrospinal fluid was investigated. The effects of mafedine were assessed in a comparative perspective with clonidine. The administration of mafedine at a dose of 2.5 mg/kg to rats after brain trauma is shown to lead to an increase in their overall motor activity and an improvement of fore- and hindlimb motor function without any negative behavioural effects. The studied compound is established to have no effect on the protein composition of the cerebrospinal fluid; however, it decreased the overall size of the damaged area by the 7th day after injury. Moreover, mafedine is shown to decrease the intensity of inflammation processes in the damaged area in rats with traumatic brain injuries. In comparison with clonidine, mafedine demonstrated a higher efficacy in most of the tests. Yohimbine abolished most of the beneficial effects of mafedine; therefore, the positive effects of mafedine are likely to be related to its action on alpha-2 adrenergic receptors.

traumatic brain injury, neuroprotective agents, alpha-2 adrenergic agonists, mafedine, clonidine

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