An experimental evaluation of the therapeutic window of the neuroprotective activity of a low-molecular nerve growth factor mimetic GK-2

Seredenin S.B.; Povarnina P.Yu.; Gudasheva T.A.

doi:https://doi.org/10.17116/jnevro20181187149

Seredenin S.B.

Zakusov Research Institute of Pharmacology, Russian Academy of Sciences, Moscow

Povarnina P.Yu.

Zakusov Research Institute of Pharmacology, Moscow, Russia

Gudasheva T.A.

Zakusov Research Institute of Pharmacology, Russian Academy of Sciences, Moscow

An experimental evaluation of the therapeutic window of the neuroprotective activity of a low-molecular nerve growth factor mimetic GK-2

Authors:

Seredenin S.B., Povarnina P.Yu., Gudasheva T.A.

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Journal: S.S. Korsakov Journal of Neurology and Psychiatry. 2018;118(7): 49‑53

DOI: 10.17116/jnevro20181187149

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To cite this article:

Seredenin SB, Povarnina PYu, Gudasheva TA. An experimental evaluation of the therapeutic window of the neuroprotective activity of a low-molecular nerve growth factor mimetic GK-2. S.S. Korsakov Journal of Neurology and Psychiatry. 2018;118(7):49‑53. (In Russ.)
https://doi.org/10.17116/jnevro20181187149

Подписка 2026 Журнал неврологии и психиатрии им. С.С. Корсакова (S.S. Korsakov Journal of Neurology and Psychiatry)

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Abstract:

Objective. To identify the time interval for the preservation of the effect of GK-2 depending on the start of administration after modeling ischemic stroke by the transient occlusion of the middle cerebral artery in rats. Material and methods. The experiments were performed on 33 wild-type male rats and 81 male Wistar rats. Animals were kept in standard conditions. Ischemic stroke was modelled by thread occlusion of the middle cerebral artery. Results and conclusion. It was found that GK-2 at a daily dose of 1 mg/kg, intraperitoneally, during 7 days statistically significantly reduces brain infarct volume by 20—60% at the first injection from 4 to 24h, with the highest effect 6—8 hours after surgery. Thus, the «therapeutic window» of GK-2 detected in the experiment is no less than 24 hours, which exceeds the existing neuroprotective agents.

Keywords:

ischemic stroke

therapeutic window

nerve growth factor

low-molecular NGF mimetic

GK-2

Authors:

Seredenin S.B.

Zakusov Research Institute of Pharmacology, Russian Academy of Sciences, Moscow

Povarnina P.Yu.

Zakusov Research Institute of Pharmacology, Moscow, Russia

Gudasheva T.A.

Zakusov Research Institute of Pharmacology, Russian Academy of Sciences, Moscow

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References:

Gusev EI, Martynov MYu, Kamchatnov PR, Yasamanova AN, Shchukin IA, Kolesnikova TI. Cerebral stroke. Consilium medicum. 2014;16(12):13-17. (In Russ.) http://con-med.elpub.ru/jour/article/view/280
Zakharov VV, Vakhnina NV. Stroke and cognitive disorders. Neurology, Neuropsychiatry, Psychosomatics. 2011;2:8-16. (In Russ.) https://doi.org/10.14412/2074-2711-2011-141
Morgan CD, Stephens M, Zuckerman SL, Waitara MS, Morone PJ, Dewan MC, Mocco J. Physiologic imaging in acute stroke: Patient selection. Interv Neuroradiol. 2015;21(4):499-510. https://doi.org/10.1177/1591019915587227
Zhu W, Cheng S, Xu G, Ma M, Zhou Z, Liu D, Liu X. Intranasal nerve growth factor enhances striatal neurogenesis in adult rats with focal cerebral ischemia. Drug Deliv. 2011;8(5):338-343. https://doi.org/10.3109/10717544.2011.557785
Yang J, Liu HJ, Yang H, Fenq PY. Therapeutic time window for the neuroprotective effects of NGF when administered after focal cerebral ischemia. Neurol Sci. 2011;32(3):433-441. https://doi.org/10.1007/s10072-011-0512-9
Gudasheva TA, Povarnina PYu, Antipova TA, Seredenin SB. A Novel Dimeric Dipeptide mimetic of the nerve growth factor exhibits pharmacological effects upon systemic administration and has no side effects accompanying the neurotrophin treatment. Neuroscience & Medicine. 2014;5:101-108. https://doi.org/10.4236/nm.2014.52013
Seredenin SB, Gudasheva TA. The development of a pharmacologically active low-molecular mimetic of the nerve growth factor. Zhurnal Nevrologii i Psihiatrii im. S.S. Korsakova. 2015;115(6):63-70. (In Russ.) https://doi.org/10.17116/jnevro20151156163-70
Gudasheva TA, Povarnina PY, Antipova TA, Firsova YN, Konstantinopolsky MA, Seredenin SB. Dimeric dipeptide mimetics of the nerve growth factor Loop 4 and Loop 1 activate TRKA with different patterns of intracellular signal transduction. J Biomed Sci. 2015;22:106. https://doi.org/10.1186/s12929-015-0198-z
Longa EZ, Weinstein PR, Carlson S, Cummins R. Reversible middle cerebral artery occlusion without craniectomy in rats. Stroke. 1989;20(1):84-91. https://doi.org/10.1161/01.STR.20.1.84
Jolkkonen J, Puurunen K, Rantakömi S, Härkönen A, Haapalinna A, Sivenius J. Behavioral effects of the alpha(2)-adrenoceptor antagonist, atipamezole, after focal cerebral ischemia in rats. Eur J Pharmacol. 2000;21:400(2-3):211-219. https://doi.org/10.1016/S0014-2999(00)00409-X
Bederson JB, Pitts LH, Germano SM, Nishimura MC, Davis RL, Bartkowski HM. Evaluation of 2,3,5-triphenyltetrazolium chloride as a stain for detection and quantification of experimental cerebral infarction in rats. Stroke. 1986;17(6):1304-1308. https://doi.org/10.1161/01.STR.17.6.1304
Sorokina IB, Gudkova AA, Geht AB. Neuroprotective Therapy of Nervous System Diseases: Possibilities of Citicoline Use. Lechebnoe delo. 2009;3:85-93. (In Russ.) http://cyberleninka.ru/article/n/neyroprotektivnaya-terapiya-zabolevaniy-nervnoy-sistemy-vozmozhnosti-primeneniya-tsitikolina
Martynov MYu, Gusev EI. Current knowledge on the neuroprotective and neuroregenerative properties of citicoline in acute ischemic stroke. J Exp Pharmacol. 2015;7:17-28. https://doi.org/10.2147/JEP.S63544
Dávalos A, Alvarez-Sabín J, Castillo J, Díez-Tejedor E, Ferro J, Martínez-Vila E, Serena J, Segura T, Cruz VT, Masjuan J, Cobo E, Secades JJ; International Citicoline Trial on acUte Stroke (ICTUS) trial investigators. Citicoline in the treatment of acute ischaemic stroke: an international, randomised, multicentre, placebo-controlled study (ICTUS trial). Lancet. 2012;380(9839):349-357. https://doi.org/10.1016/S0140-6736(12)60813-7
Jiang H, Tian S, Zeng Y, Shi J. Nerve growth factor inhibits Gd(3+)-sensitive calcium influx and reduces chemical anoxic neuronal death. J Huazhong Univ Sci Technolog Med Sci. 2008;28(4):379-382. https://doi.org/10.1007/s11596-008-0402-4
Hassanzadeh P, Arbabi E, Atyabi F, Dinarvand R. Nerve growth factor-carbon nanotube complex exerts prolonged protective effects in an in vitro model of ischemic stroke. Life Sci. 2016;0024-3205(16):30681-30686. https://doi.org/10.1016/j.lfs.2016.11.029
Park JH, Kang SS, Kim JY, Tchah H. Nerve Growth Factor Attenuates Apoptosis and Inflammation in the Diabetic Cornea. Invest Ophthalmol Vis Sci. 2016;57(15):6767-6775. https://doi.org/10.1167/iovs.16-19747
Oliveira SL, Pillat MM, Cheffer A, Lameu C, Schwindt TT, Ulrich H. Functions of neurotrophins and growth factors in neurogenesis and brain repair. Cytometry A. 2013;83(1):76-89. https://doi.org/10.1002/cyto.a.22161
Lazarovici P, Marcinkiewicz C, Lelkes PI. Cross talk between the cardiovascular and nervous systems: neurotrophic effects of vascular endothelial growth factor (VEGF) and angiogenic effects of nerve growth factor (NGF)-implications in drug development. Curr Pharm Des. 2006;12(21):2609-2622. https://doi.org/10.2174/138161206777698738
Guegan C, Onteniente B, Makiura Y, Merad-Boudia M, Ceballos-Picot I, Sola B. Reduction of cortical infarction and impairment of apoptosis in NGF-transgenic mice subjected to permanent focal ischemia. Brain Res Mol Brain Res. 1998;55(1);133-140. https://doi.org/10.1016/S0169-328X(97)00372-0
Lee TH, Kato H, Chen S-T, Kogure K, Itoyama Y. Expression of nerve growth factor and TrkA after transient focal cerebral ischemia in rats. Stroke. 1998;29(8):1687-1697. https://doi.org/10.1161/01.STR.29.8.1687
Seredenin SB, Silachev DN, Gudasheva TA, Pirogov YuA, Isaev NK. Neuroprotective effect of GK-2, a dipeptide mimetic of nerve growth factor, during experimental focal ischemia in middle cerebral artery basin. Bull Exp Biol Med. 2011;151(5):584-587. (In Russ.)