THE IMPORTANCE OF CENTRAL CHOLINERGIC SYSTEMS ACTIVATION IN TRAUMATIC BRAIN INJURY
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Keywords

central cholinergic systems; experimental traumatic brain injury; choline alfoscerate

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Ziablitsev , S., & Khudoley , S. (2020). THE IMPORTANCE OF CENTRAL CHOLINERGIC SYSTEMS ACTIVATION IN TRAUMATIC BRAIN INJURY. Medical Science of Ukraine (MSU), 16(3), 3-8. https://doi.org/10.32345/2664-4738.3.2020.1

Abstract

Relevance. It is known that in traumatic brain injury (TBI), the activity of the central cholinergic systems (CChS) is inhibited, the release of acetylcholine and the expression of cholinergic receptors decrease. The restoration of cholinoreactivity is an urgent area of research and a possible therapeutic direction.

Objective – to determine the effect of CChS activation on mortality, neurological disorders, and the activity of the pituitary-corticoadrenal system (PCAS) in the acute period of TBI.

Material and methods. TBI was simulated with a free load’s fall on a fixed animal head. To activate the CChS, rats were injected with choline alfoscerate (gliatilin, 6 mg/kg) before the injury, physiological saline was injected in the control group. Neurological deficits were assessed using the 100-point Todd scale. In blood plasma, 3, 24, 48, and 72 hours after injury, the content of adrenocorticotropic hormone and corticosterone was determined by the enzyme immunoassay method (DSL; USA). The results were statistically processed using the SPSS 11.0, MedStat, MedCalc software.

Results. Mortality in the control group was 25.0%, in the group with activation of the CChS there were no lethal cases (p<0.05). The neurological deficit in the group with CChS activation was significantly less pronounced compared to the control at all periods of observation. The hormone content had a similar dynamics: it reached a maximum after 24 hours and recovered after 72 hours, however, upon activation of the CChS, the increase was 1.4-1.5 times less (p<0.05). Thus, the use of choline alfoscerate for modeling the CChS activity led to a decrease in mortality and neurological deficit in the acute period of TBI, which was accompanied by a stabilizing PCAS function.

Conclusion. The important role of CChS in the implementation of post-traumatic stress reaction of PCAS, as well as the possibility of its pharmacological correction with choline alfoscerate, was established.

https://doi.org/10.32345/2664-4738.3.2020.1
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References

Pedachenko E.G., Semisalov S.Ya., Elskyy V.N., Kardash A.M. [Clinical epidemiology of traumatic brain injury]. Donetsk: Apex; 2002. 156 p. [in Russian]. URL: http://www.irbis-nbuv.gov.ua/cgi-bin/irbis_nbuv/cgiirbis_64.exe?Z21ID=&I21DBN=EC&P21DBN=EC&S21STN=1&S21REF=10&S21FMT=fullwebr&C21COM=S&S21CNR=20&S21P01=0&S21P02=0&S21P03=I=&S21COLORTERMS=1&S21STR=%D0%92%D0%90641198$

Levkin O.A., Goldovsky B.M., Serikov K.V. [Analysis of the provision of specialized (emergency) medical care by victims of severe traumatic brain injury]. Med urgent states. 2014; 7: 118-20. [in Ukrainian]. URL: https://cyberleninka.ru/article/n/analiz-okazaniya-spetsializirovannymi-brigadami-ekstrennoy-skoroy-meditsinskoy-pomoschi-postradavshim-s-tyazheloy-cherepno-mozgovoy

Guk A.P. [Regularities of mortality from head injuries and craniocerebral injuries in Ukraine]. Ukraine. Health Nation. 2010; 3: 48-53. [in Ukrainian]. URL: http://www.irbis-nbuv.gov.ua/cgi-bin/irbis_nbuv/cgiirbis_64.exe?I21DBN=LINK&P21DBN=UJRN&Z21ID=&S21REF=10&S21CNR=20&S21STN=1&S21FMT=ASP_meta&C21COM=S&2_S21P03=FILA=&2_S21STR=Uzn_2010_3_9

Guk A.P. [Clinical and epidemiological characteristics of traumatic brain injury in Ukraine for 1999-2008]. Ukraine. Health Nation. 2011; 2: 52-6. [in Ukrainian]. URL: http://www.irbis-nbuv.gov.ua/cgi-bin/irbis_nbuv/cgiirbis_64.exe?I21DBN=LINK&P21DBN=UJRN&Z21ID=&S21REF=10&S21CNR=20&S21STN=1&S21FMT=ASP_meta&C21COM=S&2_S21P03=FILA=&2_S21STR=Uzn_2011_2_9

Abou-El-Hassan H., Dia B., Choucair K., Eid S.A., Najdi F., Baki L., Talih F., Eid A.A., Kobeissy F. Traumatic brain injury, diabetic neuropathy and altered-psychiatric health: The fateful triangle. Med Hypotheses. 2017 Oct; 108: 69-80. DOI: https://doi.org/10.1016/j.mehy.2017.08.008.

Elskyy V.N., Kardash A.M., Gorodnik G.A. [Pathophysiology, diagnosis and intensive care of severe traumatic brain injury]. Ed. by prof. Cherniy V.I. Donetsk: New world, 2004. 200 p. [in Ukrainian]

Ziablitsev S.V., Elskyy V.M. [Syndromes of traumatic disease in traumatic brain injury]. Kramatorsk: Kashtan, 2020. 350 p. [in Ukrainian]

Laurer H.L., McIntosh T.K. Pharmacologic therapy in traumatic brain injury: update on experimental treatment strategies. Curr. Pharm. Des. 2001 Oct; 7(15): 1505-16. DOI: https://doi.org/10.2174/1381612013397285.

Nokkari A., Abou-El-Hassan H., Mechref Y., Mondello S., Kindy M.S., Jaffa A.A., Kobeissy F. Implication of the kallikrein-kinin system in neurological disorders: quest for potential biomarkers and mechanisms. Prog Neurobiol. 2018 Jun-Aug; 165-7: 26-50. DOI: 10.1016/j.pneurobio.2018.01.003.

Bortolotti P., Faure E., Kipnis E. Inflammasomes in tissue damages and immune disorders after trauma. Front Immunol. 2018 Aug 16; 9: 1900. DOI: https://doi.org/10.3389/fimmu.2018.01900

Zhao J., Hylin M.J., Kobori N., Hood K.N., Moore A.N, Pramod K., Dash P.K. Post-injury administration of galantamine reduces traumatic brain injury pathology and improves outcome. J Neurotrauma. 2018 Jan 15; 35(2): 362-74. DOI: https://doi.org/10.1089/neu.2017.5102.

Belluardo N., Mudo G., Blum M., Amato G., Fuxe K. Neurotrophic effects of central nicotinic receptor activation. J Neural Transm. 2000; Suppl. 227-45. DOI: https://doi.org/10.1007/978-3-7091-6301-6_15.

Mudo G., Belluardo N., Fuxe K. Nicotinic receptor agonists as neuroprotective/neurotrophic drugs. Progress in molecular mechanisms. J Neural Transm (Vienna). 2007 Jan; 114(1): 135-47. DOI: https://doi.org/10.1007/s00702-006-0561-z.

Kalappa B.I., Sun F., Johnson S.R., Jin K., Uteshev V.V. A positive allosteric modulator of α7 nAChRs augments neuroprotective effects of endogenous nicotinic agonists in cerebral ischaemia. Br J Pharmacol. 2013 Aug; 169(8): 1862-78. DOI: https://doi.org/10.1111/bph.12247

Gorman L.K., Fu K., Hovda D.A., Murray M, Traystman R.J. Effects of traumatic brain injury on the cholinergic system in the rat. J Neurotrauma. 1996 Aug; 13(8): 457-63. DOI: https://doi.org/10.1089/neu.1996.13.457.

Shin S.S., Dixon C.E. Alterations in cholinergic pathways and therapeutic strategies targeting cholinergic system after traumatic brain injury. J Neurotrauma. 2015 Oct 1; 32(19): 1429-40. DOI: https://doi.org/10.1089/neu.2014.3445.

Dixon C.E., Ma X., Marion D.W. Effects of CDP-choline treatment on neurobehavioral deficits after TBI and on hippocampal and neocortical acetylcholine release. J Neurotrauma. 1997 Mar; 14(3): 161-9. DOI: https://doi.org/10.1089/neu.1997.14.161.

Jonnala R.R., Buccafusco J.J. Relationship between the increased cell surface alpha7 nicotinic receptor expression and neuroprotection induced by several nicotinic receptor agonists. J Neurosci Res. 2001 Nov 15; 66(4): 565-72. DOI: https://doi.org/10.1002/jnr.10022.

Yu T.S., Kim A., Kernie S.G. Donepezil rescues spatial learning and memory deficits following traumatic brain injury independent of its effects on neurogenesis. PLoS One. 2015 Feb 25; 10(2): e0118793. DOI: https://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. Donepezil is ineffective in promoting motor and cognitive benefits after controlled cortical impact injury in male rats. J Neurotrauma. 2013 Apr 1; 30(7): 557-64. DOI: https://doi.org/10.1089/neu.2012.2782

Elskyy V.N., Ziablitsev S.V. [Modeling of traumatic brain injury]. Donetsk: New World; 2008. 140 р. [in Russian]

Elskyy VN, Ziablitsev SV. [Neurohormonal regulatory mechanisms in traumatic brain injury]. Donetsk: New World; 2008. [in Russian]

Changeux J.P. The nicotinic acetylcholine receptor: a typical 'allosteric machine'. Philos Trans R Soc Lond B. Biol Sci. 2018 Jun 19; 373(1749): 20170174. DOI: https://doi.org/10.1098/rstb.2017.0174.

Cecchini M., Changeux J.P. The nicotinic acetylcholine receptor and its prokaryotic homologues: Structure, conformational transitions & allosteric modulation. Neuropharmacology. 2015 Sep; 96 (Pt B): 137-49. DOI: https://doi.org/10.1016/j.neuropharm.2014.12.006.

Levin E.D. Complex relationships of nicotinic receptor actions and cognitive functions. Biochem Pharmacol. 2013 Oct 15; 86(8): 1145-52. DOI: https://doi.org/10.1016/j.bcp.2013.07.021.

Balkan B., Pogun S.. Nicotinic cholinergic system in the hypothalamus modulates the activity of the hypothalamic neuropeptides during the stress response. Curr Neuropharmacol. 2018; 16(4): 371-387. DOI: https://doi.org/10.2174/1570159X15666170720092442.

Hauger R.L., Dautzenberg F.M. Regulation of the stress response by corticotropin-releasing factor receptors. In: Neuroendocrinology in Physiology and Medicine. Conn P.M., Freeman M.E., editors. Totowa, New Jersey: Humana Press; 2000:261-86. DOI: 10.1007/978-1-59259-707-9_15.

Verbois S.L., Sullivan P.G., Scheff S.W., Pauly J.R. Traumatic brain injury reduces hippocampal alpha7 nicotinic cholinergic receptor binding. J Neurotrauma. 2000 Nov; 17(11): 1001-11. DOI: https://doi.org/10.1089/neu.2000.17.1001.

Kelso M.L., Wehner J.M., Collins A.C., Scheff S.W., Pauly J.R. The pathophysiology of traumatic brain injury in alpha7 nicotinic cholinergic receptor knockout mice. Brain Res. 2006 Apr 14; 1083(1): 204-10. DOI: https://doi.org/10.1016/j.brainres.2006.01.127.

Titus D.J., Johnstone T., Johnson N.H., London S.H., Chapalamadugu M., Hogenkamp D., Gee K.W., Atkins C.M. Positive allosteric modulation of the α7 nicotinic acetylcholine receptor as a treatment for cognitive deficits after traumatic brain injury. PLoS One. 2019 Oct 3; 14(10): e0223180. DOI: https://doi.org/10.1371/journal.pone.0223180.

Dash P.K., Zhao J., Kobori N., Redell J.B., Hylin M.J., Hood K.N., Moore A.N. Activation of alpha 7 cholinergic nicotinic receptors reduce blood-brain barrier permeability following experimental traumatic brain injury. J Neurosci. 2016 Mar 2; 36(9): 2809-18. DOI: https://doi.org/10.1523/JNEUROSCI.3197-15.2016.

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