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ISSN 2522-9028 (Print)
ISSN 2522-9036 (Online)
DOI: https://doi.org/10.15407/fz

Fiziologichnyi Zhurnal

is a scientific journal issued by the

Bogomoletz Institute of Physiology
National Academy of Sciences of Ukraine

Editor-in-chief: V.F. Sagach

The journal was founded in 1955 as
1955 – 1977 "Fiziolohichnyi zhurnal" (ISSN 0015 – 3311)
1978 – 1993 "Fiziologicheskii zhurnal" (ISSN 0201 – 8489)
1994 – 2016 "Fiziolohichnyi zhurnal" (ISSN 0201 – 8489)
2017 – "Fiziolohichnyi zhurnal" (ISSN 2522-9028)

Fiziol. Zh. 2020; 66(5): 64-72


STATE OF NEUROENDOCRINE SYSTEMS DURING ACTIVATION AND INHIBITION OF CENTRAL CHOLINERGIC SYSTEMS IN BRAIN INJURY

S.V. Ziablitsev1, S.O. Khudoley2

  1. Bogomolets National Medical University, Kyiv, Ukraine
  2. Medical Center for Modern Addictology “MedicoMente”, Kyiv, Ukraine
DOI: https://doi.org/10.15407/fz66.05.064

Abstract

The aim of the study was to determine the state of the neuroendocrine systems during the activation and inhibition of the central cholinergic systems (CChS) in traumatic brain injury (TBI) and their effect on mortality and neurological deficit. TBI was applied by the standard method with the free fall of metal weight on the fixed animal head. 161 white male Wistar rats were divided into three groups: in the 1st group, 0.5 ml of Ringer’s solution was injected intraperitoneally before injury (control), in the 2nd – solution of choline alfoscerate at a dose 6 mg/kg (CChS activation), in the 3rd – solution of biperidene hydrochloride at a dose 0.6 mg/kg (CChS blockade). Neurological deficits were assessed using the 100-point Todd scale. In the blood was determined the content of Adrenocorticotropic (ACTH) and Thyroid-Stimulating Hormones, Corticosterone (Cs), free Thyroxine and Triiodothyronine (fT3) by the enzyme immunoassay. It was established that in the acute period of TBI, post-traumatic stress central hypercortisolism is formed with an increase in blood levels of ACTH and Cs, and central hypothyroidism with a predominant decrease in blood fT3. The CChS activation significantly reduced mortality and neurological deficit, which was accompanied by moderate activation of ACTH and Cs and no effect on the thyroid system. The CChS blockade led to the suppression of the post-traumatic reaction of ACTH and Cs activation and the development of deep central hypothyroidism against the significant neurological deficit. Thus, the important role of CChS in the implementation of the post-traumatic stress reaction of the neuroendocrine system has been established, and the possibility of using pharmacological stimulation of the CNS with central cholinomimetics has been substantiated.

Keywords: central cholinergic systems, experimental traumatic brain injury

References

  1. Pedachenko EG, Semisalov SYa, Elskyy VN, Kardash AM. Clinical epidemiology of traumatic brain injury. Donetsk: Apex; 2002. [Russian].
  2. Levkin OA, Goldovsky BM, Serikov KV. Analysis of the provision of specialized (emergency) medical care by victims of severe traumatic brain injury. Med Urgent States. 2014;7:118-20. [Ukrainian].
  3. Guk AP. Regularities of mortality from head injuries and craniocerebral injuries in Ukraine. Health Nation. 2010; 3:48-53. [Ukrainian].
  4. Guk AP. Clinical and epidemiological characteristics of traumatic brain injury in Ukraine for 1999-2008. Ukraine. Health Nation.2011;2:52-6. [Ukrainian].
  5. Abou-El-Hassan H, Dia B, Choucair K, Eid SA, Najdi F, Baki L, Talih F, Eid AA, Kobeissy F. Traumatic brain injury, diabetic neuropathy and altered-psychiatric health: The fateful triangle. Med Hypotheses. 2017 Oct;108:69-80. CrossRef PubMed
  6. Elskyy VN, Kardash AM, Gorodnik GA. Pathophysiology, diagnosis and intensive care of severe traumatic brain injury. Ed. by prof. Cherniy V.I. Donetsk: New world, 2004. [Ukrainian].
  7. Ziablitsev SV, Elskyy VM. Syndromes of traumatic disease in traumatic brain injury. Kramatorsk: Kashtan, 2020. [Ukrainian].
  8. Laurer HL, McIntosh TK. Pharmacologic therapy in traumatic brain injury: update on experimental treatment strategies. Curr Pharm Des. 2001 Oct;7(15):1505-16. CrossRef PubMed
  9. Nokkari A, Abou-El-Hassan H, Mechref Y, Mondello S, Kindy MS, Jaffa AA, Kobeissy F. Implication of the kallikrein-kinin system in neurological disorders: quest for potential biomarkers and mechanisms. Prog Neurobiol. 2018 Jun-Aug;165-167:26-50. CrossRef PubMed PubMedCentral
  10. Bortolotti P, Faure E, Kipnis E. Inflammasomes in tissue damages and immune disorders after trauma. Front Immunol. 2018 Aug 16;9:1900. CrossRef PubMed PubMedCentral
  11. Zhao J, Hylin MJ, Kobori N, Hood KN, Moore AN, Pramod K, Dash PK. Post-injury administration of galantamine reduces traumatic brain injury pathology and improves outcome. J Neurotrauma. 2018 Jan 15;35(2):362-74.
  12. Belluardo N, Mudo G, Blum M, Amato G, Fuxe K. Neurotrophic effects of central nicotinic receptor activation. J Neural Transm. 2000;Suppl.227-245. CrossRef PubMed
  13. 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. CrossRef PubMed
  14. Kalappa BI, Sun F, Johnson SR, Jin K, Uteshev VV. A positive allosteric modulator of α7 nAChRs augments neuroprotective effects of endogenous nicotinic agonists in cerebral ischemia. Br J Pharmacol. 2013 Aug;169(8):1862-78. CrossRef PubMed PubMedCentral
  15. Gorman LK, Fu K, Hovda DA, Murray M, Traystman RJ. Effects of traumatic brain injury on the cholinergic system in the rat. J Neurotrauma. 1996 Aug;13(8):457-63. CrossRef PubMed
  16. Shin SS, Dixon CE. Alterations in cholinergic pathways and therapeutic strategies targeting cholinergic system after traumatic brain injury. J Neurotrauma. 2015 Oct 1;32(19):1429-40. CrossRef PubMed PubMedCentral
  17. Dixon CE, Ma X, Marion DW. 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. CrossRef PubMed
  18. Jonnala RR, Buccafusco JJ. 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. CrossRef PubMed
  19. Yu TS, Kim A, Kernie SG. 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. CrossRef PubMed PubMedCentral
  20. Shaw KE, Bondi CO, Light SH, Massimino LA, McAloon RL, Monaco CM, Kline AE. 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. CrossRef PubMed PubMedCentral
  21. Tudor RM, Thompson CJ. Posterior pituitary dysfunction following traumatic brain injury: review. Pituitary. 2019 Jun;22(3):296-304. CrossRef PubMed
  22. Martino EA, Baiardo Redaelli M, Sardo S, Lembo R, Giordano VF, Winterton D, Ruggeri L, Hajjar LA, Zangrillo A, Landoni G. Steroids and survival in critically ill adult patients: A meta-analysis of 135 randomized trials. J Cardiothorac Vascul Anesth. 2018 Oct;32(5):2252-60. CrossRef PubMed
  23. Elskyy VN, Ziablitsev SV. Neurohormonal regulatory mechanisms in traumatic brain injury. Donetsk: New World; 2008. [Russian].
  24. Tritos NA, Yuen KC, Kelly DF; AACE Neuroendocrine and Pituitary Scientific Committee. American Association of Clinical Endocrinologists and American College of Endocrinology Disease State clinical review: a neuroendocrine approach to patients with traumatic brain injury. Endocrinol Pract. 2015 Jul;21(7):823-31. CrossRef PubMed
  25. Elskyy VN, Ziablitsev SV. Modeling of traumatic brain injury. Donetsk: New World; 2008. [Russian].

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