Українська Русский English

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. 2017; 63(4): 56-63


EFFECTS OF NDMA RECEPTOR ADEMOL ON FUNCTIONS AND APOPTOSIS IN VISUAL CORTEX AFTER SUBARACHNOID HEMORRHAGE IN RATS

O.A. Khodakovskyi, I.L. Chereshniuk, O.I. Alchuk, L.I. Marynych, R.A. Kravets, O.V. Khodakivska

    National Pirogov Memorial Medical University, Vinnytsya, Ukraine
DOI: https://doi.org/10.15407/fz63.04.056

Abstract

Using model of hemorrhagic stroke in rats (heparinized autologous blood was injected into the subarachnoid space at a dose of 0.1 ml/100 g), we discovered that 21 days course of intravenous therapy with 1% solution of 1-adamantiloxy- 3-morpholino-2-propanolhydrochloride (ademol) at a dose of 2 mg/kg was more effective to reduce neurological deficit (from severe to moderate by stroke-index, p<0.05) and improve mnemotropic activity in the test of passive avoidance compared to nimodipine at a dose of 30 mg/kg. These findings proved neuroprotective properties of ademol. Therapy with ademol as well as with reference drug in the acute phase of subarachnoid hemorrhage (4th day) resulted in a decrease in the number of cells with fragmented DNA in the visual cortex in rats. The results of our study indicated anti-apoptotic action of ademol on the cortical neurons after hemorrhagic stroke. Taking into account pronounced mnemotropic and anti-apoptotic effects of ademol, it has been classified as a primary neuroprotective drug and can be used as pathogenetic therapeutic agent to prevent early cell death after stroke in human.

Keywords: ademol; nimodipine; subarachnoid hemorrhage; apoptosis; neurological deficit; memory; neuroprotection; rats.

References

  1. Lipton SA. Failures and successes of NMDA receptor antagonists: molecular basis for the use of open-channel blockers like memantine in the treatment of acute and chronic neurologic insults. NeuroRx. 2004 Jan;1(1):101-10. CrossRef PubMed PubMedCentral
  2.  
  3. Makotrova TA, Trusova NA, Shrader NI, Levin OS. [Neuroprotective potential of akatinol-memantine in ischemic stroke]. Zh Nevrol Psikhiatr Im S.S. Korsakova. 2013;113(7 Pt 2):82-5. [Russian].
  4.  
  5. Mirzoyan RS, Gan'shina TS, Maslennikov DV, Kovalev GI, Zimin IA, Pyatin BM, et al. Cerebrovascular and neuroprotective effects of adamantine derivative. Biomed Res Int. 2014;2014:586501. CrossRef PubMed PubMedCentral
  6. Hoque A, Hossain MI, Ameen SS, Ang CS, Williamson N, Ng DC, et al. A beacon of hope in stroke therapy-blockade f pathologically activated cellular events in excitotoxic neuronal death as potential neuroprotective strategies.Pharmacol Ther. 2016 ;160:159-79. doi: 10.1016/j.pharmthera.2016.02.009. CrossRef  
  7. Chen ZZ, Yang DD, Zhao Z, Yan H, Ji J, Sun XL. Memantine mediates neuroprotection via regulating neurovascular unit in a mouse model of focal cerebral ischemia. Life Sci. 2016 Apr 1;150:8-14. doi: 10.1016/j.lfs.2016.02.081. Epub 2016 Feb 23. CrossRef  
  8. Statinova EA, Cherniy TV, Tkacheva EL, Kugler SE. Application of complex treatment of neuroprotection in ischemic stroke. Ukrai'ns'kyj zhurnal ekstremal'noi' medycyny imeni G.O.Mozhajeva. 2010;11(4):110-16. [Russian].
  9.  
  10. Germanò A, Caffo M, Angileri FF, Arcadi F, NewcombFernandez J, Caruso G, et al. NMDA receptor antagonist felbamate reduces behavioral deficits and bloodbrain barrier permeability changes after experimental subarachnoid hemorrhage in the rat. J Neurotrauma. 2007 Apr;24(4):732-44. doi: 10.1089/neu.2006.0181. PubMed PMID: 17439355. CrossRef  
  11. Hazell AS. Excitotoxic mechanisms in stroke: an update of concepts and treatment strategies. Neurochem Int. 2007 Jun;50(7-8):941-53. doi: 10.1016/j.neuint.2007.04.026. Epub 2007 May 10. PubMed PMID: 17576023. CrossRef  
  12. Liu X, Hunter C, Weiss HR, Chi OZ. Effects of blockade of ionotropic glutamate receptors on blood-brain barrier disruption in focal cerebral ischemia. Neurol Sci. 2010 Dec;31(6):699-703. CrossRef PubMed
  13.  
  14. Montagne A, Hébert M, Jullienne A, Lesept F, Le Béhot A, Louessard M, et al. Memantine improves safety of thrombolysis for stroke. Stroke. 2012 Oct;43(10):2774-81. CrossRef PubMed
  15.  
  16. Im DS, Jeon JW, Lee JS, Won SJ, Cho SI, Lee YB, et al. Role of the NMDA receptor and iron on free radical production and brain damage following transient middle cerebral artery occlusion. Brain Res. 2012 May 21;1455:114-23. doi: 10.1016/j.brainres.2012.03.025. Epub 2012 Mar 17. CrossRef  
  17. Righy C, Bozza MT, Oliveira MF, Bozza FA. Molecular, Cellular and Clinical Aspects of Intracerebral Hemorrhage: Are the Enemies Within? Curr Neuropharmacol. 2016;14(4):392-402. PubMed PMID: 26714583; PubMed PMCID: PMC4876594.
  18.  
  19. Khodakivskyi OA. [Comparative impact assessment adamantane derivatives of compounds UK-1 and UK-4 on the activity of NMDA-receptor]. Clinical Pharmacy. 2011;15(4):60-3. [Ukrainian]. 
  20. Buresh Ja, Bureshova O, Hjuston D. [Methods and basic experiments on study of brain and behavior]. Moscow: Vysshaja shkola, 1991. 398 p. [Russian].
  21. McGrow CP. Experimental Cerebral Infarction Effects of Pentobarbital in Mongolian Gerbils. Arch Neurol. 1977 Jun;34(6):334-6. CrossRef  
  22. Mushkambarov NN, Kuznetsov SL. [Molecular biology: a manual for students of medical schools]. Moscow: MIA, 2007. 536 p. [Russian].
  23.  
  24. Portier BP, Ferrari DC, Taglialatela G. Rapid assay for quantitative measurement of apoptosis in cultured cells and brain tissue. J Neurosci Methods. 2006 Jul 15;155(1):134-42. CrossRef PubMed
  25.  
  26. Babu CS, Ramanathan M. Post-ischemic administration of nimodipine following focal cerebral ischemic-reperfusion injury in rats alleviated excitotoxicity, neurobehavioural alterations and partially the bioenergetics. Int J Dev Neurosci. 2011 Feb;29(1):93-105. CrossRef PubMed
  27.  
  28. Kotel'nykova SO, Nepoklonov AV, Kokshenev YY, Yvanova EA, Krayneva VA, EA Val'dman, et al. [Comparative study of himantane and amantadine effects in experimental intracerebral posttraumatic hematoma]. Zh Nevrol Psikhiatr Im S.S. Korsakova. 2012;112(9):63-6. [Russian].
  29.  
  30. Khodakivskyi OA. [Estimation of influence of experimental therapy of ademol on intensity of flow of destructive changes in membrane of neurons in mongolian herbels under condition of acute cerebral ischemia]. Reports of Morphology. 2011;17(1):62-5. [Ukrainian].
  31.  
  32. Khodakivskyi OA, Chereschnyuk IL. Investigation of influence of derivate of adamantan ademol on fragmentation of DNA nucleuses of neurons of frontal lobes of cortex under ischemia reperfusion of brain in rats. Ukrains'kyi visnyk psykhonevrolohii. 2013;21(1):26-28. [Ukrainian].
  33.  
  34. Khodakovskyi OA, Pavlov SV, Buchtiyarova NV. Modulation of apoptosis with ademol under condition of modeling of acute disorder of encephalic circulation by influence on expression of early reacting gens. Nauchnie vedomosty Belhorodskoho natsyonal'noho unyversyteta. 2013;22(11):155-159. [Russian].
  35.  

© National Academy of Sciences of Ukraine, Bogomoletz Institute of Physiology, 2014-2020.