Carbacetam influence on cognitive disturbances in experimental brain injury, possible vasopressin role

S.V. Ziablitsev, A.O. Starodubskaya, S.L. Bogza

Abstract


Background. Cognitive disturbances in traumatic brain injury (TBI) are urgent and understudied problem, as the extent of central nervous system suppression characterizes the severity of TBI and defines its outcome. The new pharmacological agent carbacetam belongs to the anxiolytics, endogenous gamma-aminobutyric acid (GABA) benzodiazepine receptor complex modulators, derivatives of β-carboline. The use of GABA system modulators in TBI can be a perspective direction of cognitive disturbances correction. The aim of this work was to define carbacetam influence on cognitive disturbances in experimental TBI. Materials and methods. The research includes 45 white outbred rat males; TBI has been reproduced by V.M. Yelskyi and S.V. Ziablitsev method (2005). Study groups with TBI included 15 animals each: group 1 — carbacetam introduction (5 mg/kg body mass), group 2 — actovegin introduction (16 mg/kg body mass), comparison (control) group — introduction of 1 ml of physiological solution intraperitoneally within 10 days after a trauma. Cognitive disorders are investigated by techniques: open field test, hole-board test, radial arm maze on days 1, 3, 7, 14 and 30 after the trauma. Results. In comparison group during the entire period of observation, a sharp decrease in the quantity of the crossed squares and the examined holes is noted that indicated total absence of motivation, curiosity and cognitive abilities after TBI. The sharp augmentation of latent time of transition to the dark hole indicated a disorientation and impossibility to find a hole independently (cognitive disturbances). From all indicators, only the hole-board test was spontaneously restored. Faster renewal dynamics of cognitive functions was noted in the study group 1, where indicators of an approximate motor performance began renewed in a week. In a month, a significant increase in the number of successful enters in sleeves as compared to the control group is received (by 41.0 %). Renewal of cognitive processes in rats under the actovegin influence began only two weeks after TBI. In a month, indicators of an approximate motor performance in the open field renewed, but not completely (the quantity of the crossed squares was significantly increased, but didn’t reach the initial level (p < 0.05). The quantity of the examined holes was significantly smaller (by 23.3 %) in comparison with the study group 1 (p < 0.05). It indicated a smaller effect of actovegin in comparison with carbacetam. Under the carbacetam influence, there was a vasopressin secretion renewal that had antistress action and, in our opinion, caused positive effect of the drug on cognitive and memory functions of animals with TBI. Conclusions. The obtained data indicated a reliable renewal of cognitive and memory processes in rats with TBI under the carbacetam influence within 30 days of observation that could be mediated by the restoration of vasopressin neurosecretion.


Keywords


traumatic brain injury; carbacetam; cognitive disturbances; vasopressin

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DOI: https://doi.org/10.22141/1608-1706.2.18.2017.102559

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