Carbacetam effect on processes of neurodestruction in hippocampus during experimental traumatic brain injury.
DOI:
https://doi.org/10.26641/1997-9665.2017.2.12-18Keywords:
traumatic brain injury, hippocampus, S100, NSE, GFAP, carbacetam.Abstract
Background. Treatment of traumatic brain injury (TBI) is one of the most relevant problems in modern medicine. TBI is accompanied by not only physical damage, but also psychical disorders, which together greatly worsen the quality of life of patients. Even light injury causes cognitive, affective (including depression, anxiety and psychosis) and behavioral disorders. Cognitive functions, in particular memory and ability to study, are regulated by the hippocampus. This part of the brain is very sensitive to traumatic effects, whereupon the patients get different neurocognitive disorders. The key role in TBI pathogenesis belongs to destructive changes in the nervous tissue of the brain that is manifested as the damage of neurons and glial cells. Carbacetam seems to be the promising drug for correction of TBI consequences, making antihypoxic, antiamnestic, anxiolytic and anti-shock effects. Due to the number of helpful effects carbacetam is interesting in the aspect of its influence on morphological and immunohistochemical features of the hippocampal nervous tissue after TBI. Objective. To investigate the carbacetam effect on processes of neurodestruction in hippocampus during experimental traumatic brain injury. Methods: physiological, histological, immunohistochemical. Results. The morphological and immunohistological study of the rat hippocampus showed: 1. The СА3 region in the rat hippocampus of the control group demonstrates divers destructive features: рartial loss of neurons, nuclei swelling and unclarity of the apical dendrites, рolymorphic changes of the chromatophilic neuronal substance in the form of the focal chromatolysis and chromatin condensation. 2. In the control group there is quite intense expression of GFAP, NSE and S100 in the СА3 region of the hippocampus, which demonstrates the destructive changes in the astrocytes (GFAP and S100) and, at the same time, normal metabolism in the neurons (NSE). 3. After carbacetam administration the СА3 region of the hippocampus keeps the same morphological characteristics, as in the control group, but the destructive changes are less represented: majority of the neurons have round light nuclei and distinct dendrites; almost absence of the cells with features of focal chromatolysis and chromatin condensation. 4. The nervous tissue in the СА3 region of the rat hippocampus after carbacetam administration is characterized by high expression of GFAP, NSE and S100, like in the control group. The marked expression of the neuromarkers GFAP and S100 displays the destructive changes in the astrocytes, and high of NSE correlates with the normal neuronal metabolism. Conclusion. TBI is manifested in different destructive features in the hippocampal nervous tissue. Carbacetam ambiguously effects on the hippocampal nervous tissue, partly correcting destructive changes in the neurons only, but not in the glial cells. The carbacetam effect occurs mainly in morphological changes of the neurons, while there are no any immunohistochemical changes in comparison with the control group.
References
- Reis C, Wang Y, Akyol O, Ho WM, Ap-plegate R, Stier G, MartinR, Zhang JH. [What’s New in Traumatic Brain Injury: Update on Tracking, Monitoring and Treatment] Int J Mol Sci. 2015;16(6):11903-65.
- Li M, Zhao Z, Yu G, Zhang J. [Epidemiol-ogy of Traumatic Brain Injury over the World: A Systematic Review] Gen Med. (Los Angel). 2016;4(5):1-13.
- Rubin RD, Watson PD, Duff MC, Cohen NJ. [The role of the hippocampus in flexible cogni-tion and social behavior] Front Hum Neurosci. 2014;8:742.
- Zhou H, Chen L, Gao X, Luo B, Chen J. [Moderate Traumatic Brain Injury Triggers Rapid Necrotic Death of Immature Neurons in the Hippocampus] J Neuropathol Exp Neurol. J Neuropathol Exp Neurol. 2012;71(4):348-59.
- McKee AC, Daneshvar DH. [The neuropa-thology of traumatic brain injury]. Handb Clin Neurol. Handb Clin Neurol. 2015;127:45-66.
- Maia PD, Kutz JN. [Reaction time impair-ments in decision-making networks as a diagnostic marker for traumatic brain injuries and neurological diseases] J Comput Neurosci. 2017;42(3):323-47.
- Kochanek PM, Jackson TC, Ferguson NM, Carlson SW, Simon DW, Brockman EC, Hülya Bayir JJ, Poloyac SM, Wagner AK, Kline AE, Empey PE, Clark RSB, Jackson EK, Dixon CE. [Emerging Therapies in Traumatic Brain Injury]. Semin Neurol. 2015;35(1):83-100.
- Xiong Y, Zhang Y, Mahmood A, Chopp M. [Investigational agents for treatment of traumatic brain injury]. Expert Opin Investig Drugs. 2015;24(6):743-60.
- Kibalny AV, Dulenko VI, Khabarov KM. [New high-effective neuroprotector – carbacetam]. Drugs of the future. Brussel. 2010; Suppl. A, 35: 198.
- Singh HV, Pandey A, Shrivastava AK, Raizada A, Singh SK, Singh N. [Prognostic value of neuron specific enolase and IL-10 in ischemic stroke and its correlation with degree of neurological deficit] Clin Chim Acta. 2013;419:136-8.
- Yardimoglu M, Ilbay G, Dalcik C, Sahin D, Ates N. [Immunocytochemistry of neuron specific enolase (NSE) in the rat brain after single and re-peated epileptic seizures]. Int J Neurosci. 2008;118(7):981-93.
- Wolf H, Frantal S, Pajenda GS, Salameh O, Widhalm H, Hajdu S, Sarahrudi K. [Predictive value of neuromarkers supported by a set of clinical criteria in patients with mild traumatic brain injury: S100B protein and neuron-specific enolase on trial: clinical article]. J Neurosurg. 2013;118(6):1298-303.
- Elskyy VN, Ziablitsev SV. [Design of brain injury]. Donetsk: Publishing by New World; 2008. 260 р. Russian.
- Dulenko VI, Komissarov IV, Doljenko AT, Nikolukin UA. [β-Carbolines. Chemistry and Neu-robiology]. Kiev: Nauk. Dumka; 1992. 216 р. Rus-sian.
- Christian KM, Miracle AD, Wellman CL, Nakazawa K. [Chronic stress-induced hippocampal dendritic retraction requires CA3 NMDA receptors] Neuroscience. 2011;174:26-36.
- Gupta SK, Behera K, Pradhan CR, Mandal AK, SethyK, Behera D, Shinde KP. [Studies of the macroscopic and microscopic morphology (hippo-campus) of brain in Vencobb broiler]. Vet World. 2016;9(5):507-11.
- Hevner RF. [Evolution of the Mammali-an Dentate Gyrus] J Comp Neurol. 2016;524(3): 578-94.
- Kulbe JR, Geddes JW. [Current status of fluid biomarkers in mild traumatic brain injury]. Exp Neurol. 2016;275(3):334-52.
- Bogoslovsky T, Gill J, Jeromin A, DavisC, Diaz-Arrastia R. [Fluid Biomarkers of Traumatic Brain Injury and Intended Context of Use]. Diagnostics (Basel). 2016;6(4):37.
- Douglas-Escobar M, Weiss MD. [Biomarkers of Hypoxic-Ischemic Encephalopathy in Newborns]. Front Neurol. 2012;3:144.
- Chvatal А, Anderova M, Neprasova H. [Pathological Potential of Astroglia]. Physiol Res. 2008;57(3):101-10.
- Vedunova MV, Terentieva KA, Shchelchkova NA, Kosareva MA, Mishchenko TA, Khaletskaya OV, Mukhina V. [Determining Concentration of Neurotrophic Factors and Neuron specific Enolase in the blood of Newborns with Central Nervous system Damages as a New Approach in Clinical Diagnostics] СТМ. 2015;7(2):25-30.
Downloads
How to Cite
Issue
Section
License
Copyright (c) 2018 Morphologia

This work is licensed under a Creative Commons Attribution 4.0 International License.
The authors reserve the right to authorship of their work and transfer to the Journal the right to the first publication of this work under the terms of a license Creative commons Attribution 4.0 International (CC BY 4.0), which allows other people to freely distribute the published work with a mandatory reference to the authors of the original work and the first publication of the work in this journal.By submitting a manuscript to the editorial office of the Journal ‘Morphologia’ authors agree to transfer the rights to protect and use the manuscript (all supplemental materials, particularly protected objects such as photos, drawings, diagrams, tables, etc.), including the reproduction in the press and distribution via the Internet; translation of the manuscript into any language; export and import of journal copies with the Authors’ article in order to make it available for public. Authors convey the rights mentioned above to the editorial office without any temporal or territorial limitation all over the world.
The Authors guarantee that they have the exclusive rights to use the material transferred to editorial office. Editors are not responsible to third parties for contraventions of warranty given by the Authors. The considered rights are transferred to the editorial office since the moment when the current issue is signed for publishing. Reproduction of materials published in the Journal by other individuals and legal entities is possible only with the consent of Editorial office, with the obligatory indication of the full bibliographic reference of the primary publication. The Authors reserve the right to use the published material, its fragments and parts for teaching materials, oral presentations, dissertation thesis prepararion with obligatory bibliographic citation of the original paper. Electron copy of the published article, downloaded from official journal web-site in .pdf format may be put by authors on the official web-site of their institutions, any other official resources with open access.
