Neurological impairments due to traumatic, vascular, or neurodegenerative brain dis-eases have a high prevalence worldwide. Among them are motor, cognitive, and mentaldisorders, which have a serious negative impact on the working and social activities ofthe patients. This calls for the search and development of novel effective neuroprotectiveagents. Previous studies have shown the pyrimidine-derived α2-adrenergic agonistmafedine to be highly effective for the amelioration of neurological deficits in experi-mental traumatic brain injury (TBI) in rats. Despite the results of the previous works fa-vouring the major role of the α2 adrenergic receptor activation in the mechanism of ac-tion of mafedine, the search for additional molecular targets is an important part of thedevelopment of any drug to be used in clinical practice. In this work, we evaluated the ef-fects of 7 day-long course administration of mafedine (2.5 mg/kg b.w.) on the expressionof brain-derived neurotrophic factor (BDNF), the proinf lammatory cytokines interleu-kin (IL)-1β, -6, tumour necrosis factor (TNF)-α, and the α2A, α2B, and α2Cα2-ad-renergic receptor subtypes in the brain cortex of rats subjected to TBI, using the reverse-transcription real-time polymerase chain reaction method. TBI was modelled by thecontrolled cortical impact technique in an open area of sensorimotor cortex of the leftbrain hemisphere. Behavioural alterations in the injured animals were assessed in theOpen field test, and the fore- and hindlimb motor function, in the Limb placing, Cylin-der, and Beam walking tests. Our experiments show that TBI causes severe motor im-pairments as well as decreases exploration in rats. Besides, at post-TBI day 7, a reductionin the expression of all analyzed genes is seen, which is the most pronounced in the contralateral (uninjured) hemisphere. Course administration of mafedine (2.5 mg/kg b.w.)resulted in moderate stimulation of the injured rats’ behaviour, increased exploratory ac-tivity compared to controls, and improved sensorimotor deficit as assessed by the Beamwalking test. Gene expression analysis results indicated that mafedine decreased α2B-adren-ergic receptor, TNF-α, and IL-6 expression in the injured hemisphere. At the sametime, compared to rats with TBI having received no treatment, mafedine-treated ani-mals exhibited higher α2B-adrenergic receptor and IL-1β expression in the injured rath-er than the intact hemisphere. These results confirm the previously observed neuro-protective activity of mafedine and imply that it may exert its effects via suppression ofα2B-adrenergic receptor and proinf lammatory cytokine expression in the injured brainhemisphere, at the same time increasing their expression in the intact one.