ANALYSIS OF THE ROLE OF CENTRAL CHOLINOREACTIVITY IN EXPERIMENTAL TRAUMATIC BRAIN INJURY

Keywords: central cholinergic systems, experimental traumatic brain injury, neurological deficit

Abstract

The aim of the research. To study effects of activation and inhibition of the central cholinergic systems (CCS) in traumatic brain injury (TBI).

Studied problem. To investigate the influence of the reactivity of the central cholinergic systems on the course of the acute period of traumatic brain injury, in an acute experiment on laboratory animals in vivo.

The main scientific results. It was found that in the acute period of TBI (the first three days), both activation and blockade of CCS led to a decrease in mortality, which was statistically confirmed only for their activation. The control group was characterized by the progression of neurological deficit, which was realized due to motor disorders and reflex sphere. Upon activation of the CCS, the degree of neurological deficit was significantly less than in other groups, but, nevertheless, it increased from 48 hours after the injury, as regards behavioral and consciousness disorders. Inhibition of cholinergic systems led to a sharp increase in neurological deficit in all areas immediately after injury, to a greater extent due to reflex disorders. This, together with a high mortality rate, indicated a negative effect of the pharmacological shutdown of CCS in TBI.

The area of practical use of the research results. The obtained results will allow a deeper study of the influence of the central cholinergic systems on the course and descent of TBI. To develop effective methods of pharmacological correction in the treatment of patients in the acute period of TBI.

Innovative technological product: pathogenetically substantiated medical treatment of the acute period of traumatic brain injury, development of new methods of pharmacological neuroprotection for persons with a priori high risk of injury, development of effective options for reducing mortality and disability from TBI.

Scope of the innovative technological product. The important role of CCS in the realization of the response of the central nervous system to TBI was established, and the possibility of using pharmacological stimulation of the central nervous system with cholinomimetics of the central type of action was justified.

Downloads

Download data is not yet available.

References

Dewan, M. C., Rattani, A., Gupta, S., Baticulon, R. E., Hung, Y.-C., Punchak, M. Et. al. (2019). Estimating the global incidence of traumatic brain injury. Journal of Neurosurgery, 130 (4), 1080–1097. doi: http://doi.org/10.3171/2017.10.jns17352

James, S. L., Theadom, A., Ellenbogen, R. G., Bannick, M. S., Montjoy-Venning, W., Lucchesi, L. R. et. al. (2019). Global, regional, and national burden of traumatic brain injury and spinal cord injury, 1990–2016: a systematic analysis for the Global Burden of Disease Study 2016. The Lancet Neurology, 18 (1), 56–87. doi: http://doi.org/10.1016/s1474-4422(18)30415-0

Khellaf, A., Khan, D. Z., Helmy, A. (2019). Recent advances in traumatic brain injury. Journal of Neurology, 266 (11), 2878–2889. doi: http://doi.org/10.1007/s00415-019-09541-4

Laccarino, C., Carretta, A., Nicolosi, F., Morselli, C. (2018). Epidemiology of severe traumatic brain injury. Journal of Neurosurgical Science, 62 (5), 535–541. doi: http://doi.org/10.23736/S0390-5616.18.04532-0

Ovsyannikov, D. M., Chekhonatsky, A. A., Kolesov, V. N., Bubashvili, A. I. (2012). Social and epidemiological aspects of craniocerebral trauma (review). Saratov journal of medical scientific research, 8 (3), 777–785.

Findings on Formerly State-Financed Institutions in the Donetsk and Luhansk Regions (2015). Organization for Security and Co-operation in Europe. OSCE. Thematic report, 17. Available at: https://www.osce.org/ukraine-smm/148326?download=true

Abou-El-Hassan, H., Dia, B., Choucair, K., Eid, S. A., Najdi, F., Baki, L. et. al. (2017). Traumatic brain injury, diabetic neuropathy and altered-psychiatric health: The fateful triangle. Medical Hypotheses, 108, 69–80. doi: http://doi.org/10.1016/j.mehy.2017.08.008

Elskii, V. N., Kardash, A. M., Gorodnik, G. A.; Chernii, V. I. (Ed.) (2004). Patofiziologiia, diagnostika i intensivnaia terapiia tiazheloi cherepno-mozgovoi travmy. Donetsk: Novii mir, 200.

Ziablitsev, S. V., Elskii, V. M. (2020). Sindromy travmaticheskoi bolezni pri cherepno-mozgovoi travme. Kramatorsk: Kashtan, 350.

Laurer, H., McIntosh, T. (2001). Pharmacologic Therapy In Traumatic Brain Injury: Update On Experimental Treatment Strategies. Current Pharmaceutical Design, 7 (15), 1505–1516. doi: http://doi.org/10.2174/1381612013397285

Nokkari, A., Abou-El-Hassan, H., Mechref, Y., Mondello, S., Kindy, M. S., Jaffa, A. A., Kobeissy, F. (2018). Implication of the Kallikrein-Kinin system in neurological disorders: Quest for potential biomarkers and mechanisms. Progress in Neurobiology, 165-167, 26–50. doi: http://doi.org/10.1016/j.pneurobio.2018.01.003

Bortolotti, P., Faure, E., Kipnis, E. (2018). Inflammasomes in Tissue Damages and Immune Disorders After Trauma. Frontiers in Immunology, 9. doi: http://doi.org/10.3389/fimmu.2018.01900

Zhao, J., Hylin, M. J., Kobori, N., Hood, K. N., Moore, A. N., Dash, P. K. (2018). Post-Injury Administration of Galantamine Reduces Traumatic Brain Injury Pathology and Improves Outcome. Journal of Neurotrauma, 35 (2), 362–374. doi: http://doi.org/10.1089/neu.2017.5102

Belluardo, N., Mudo, G., Blum, M., Amato, G., Fuxe, K. (2000). Neurotrophic effects of central nicotinic receptor activation. Advances in Research on Neurodegeneration, 227–245. doi: http://doi.org/10.1007/978-3-7091-6301-6_15

Mudo, G., Belluardo, N., Fuxe, K. (2006). Nicotinic receptor agonists as neuroprotective/neurotrophic drugs. Progress in molecular mechanisms. Journal of Neural Transmission, 114 (1), 135–147. doi: http://doi.org/10.1007/s00702-006-0561-z

Kalappa, B. I., Sun, F., Johnson, S. R., Jin, K., Uteshev, V. V. (2013). A positive allosteric modulator of α7 nAChRs augments neuroprotective effects of endogenous nicotinic agonists in cerebral ischaemia. British Journal of Pharmacology, 169 (8), 1862–1878. doi: http://doi.org/10.1111/bph.12247

Gorman, L. K., Fu, K., Hovda, D. A., Murray, M., Traystman, R. J. (1996). Effects of Traumatic Brain Injury on the Cholinergic System in the Rat. Journal of Neurotrauma, 13 (8), 457–463. doi: http://doi.org/10.1089/neu.1996.13.457

Shin, S. S., Dixon, C. E. (2015). Alterations in Cholinergic Pathways and Therapeutic Strategies Targeting Cholinergic System after Traumatic Brain Injury. Journal of Neurotrauma, 32 (19), 1429–1440. doi: http://doi.org/10.1089/neu.2014.3445

Dixon, C. E., Ma, X., Marion, D. W. (1997). Effects of CDP-Choline Treatment on Neurobehavioral Deficits after TBI and on Hippocampal and Neocortical Acetlycholine Release. Journal of Neurotrauma, 14 (3), 161–169. doi: http://doi.org/10.1089/neu.1997.14.161

Jonnala, R. R., Buccafusco, J. J. (2001). Relationship between the increased cell surface ?7 nicotinic receptor expression and neuroprotection induced by several nicotinic receptor agonists. Journal of Neuroscience Research, 66 (4), 565–572. doi: http://doi.org/10.1002/jnr.10022

Yu, T.-S., Kim, A., Kernie, S. G. (2015). Donepezil Rescues Spatial Learning and Memory Deficits following Traumatic Brain Injury Independent of Its Effects on Neurogenesis. Plos One, 10 (2), e0118793. doi: http://doi.org/10.1371/journal.pone.0118793

Shaw, K. E., Bondi, C. O., Light, S. H., Massimino, L. A., McAloon, R. L., Monaco, C. M., Kline, A. E. (2013). Donepezil Is Ineffective in Promoting Motor and Cognitive Benefits after Controlled Cortical Impact Injury in Male Rats. Journal of Neurotrauma, 30 (7), 557–564. doi: http://doi.org/10.1089/neu.2012.2782

Elskii, V. N., Ziablitsev, S. V. (2008). Modelirovanie cherepno-mozgovoi travmy. Donetsk: Novii Svet, 140.

Changeux, J.-P. (2018). The nicotinic acetylcholine receptor: a typical “allosteric machine.” Philosophical Transactions of the Royal Society B: Biological Sciences, 373 (1749), 20170174. doi: http://doi.org/10.1098/rstb.2017.0174

Abou-El-Hassan, H., Dia, B., Choucair, K., Eid, S. A., Najdi, F., Baki, L. et. al. (2017). Traumatic brain injury, diabetic neuropathy and altered-psychiatric health: The fateful triangle. Medical Hypotheses, 108, 69–80. doi: http://doi.org/10.1016/j.mehy.2017.08.008

Laurer, H., McIntosh, T. (2001). Pharmacologic Therapy In Traumatic Brain Injury: Update On Experimental Treatment Strategies. Current Pharmaceutical Design, 7 (15), 1505–1516. doi: http://doi.org/10.2174/1381612013397285

Levin, E. D. (2013). Complex relationships of nicotinic receptor actions and cognitive functions. Biochemical Pharmacology, 86 (8), 1145–1152. doi: http://doi.org/10.1016/j.bcp.2013.07.021

Verbois, S. L., Sullivan, P. G., Scheff, S. W., Pauly, J. R. (2000). Traumatic Brain Injury Reduces Hippocampal α7 Nicotinic Cholinergic Receptor Binding. Journal of Neurotrauma, 17 (11), 1001–1011. doi: http://doi.org/10.1089/neu.2000.17.1001


👁 93
⬇ 79
Published
2020-10-31
How to Cite
Khudoley, S. (2020). ANALYSIS OF THE ROLE OF CENTRAL CHOLINOREACTIVITY IN EXPERIMENTAL TRAUMATIC BRAIN INJURY. ScienceRise, (5), 31-39. https://doi.org/10.21303/2313-8416.2020.001456
Section
Innovative technologies in healthcare