Neurotrophic peptides of сerebrolysin as a basis for anticonvulsant effect of the drug

Close metadata

Recommended articles:

Cognitive impairment in patients with arterial hypertension. S.S. Korsakov Journal of Neurology and Psychiatry. 2024;(4-2):41-48

Cognitive impairment in post-traumatic stress disorder. S.S. Korsakov Journal of Neurology and Psychiatry. 2024;(5):69-74

Pharmacological effects of fonturacetam (Actitropil) and prospects for its clinical use. S.S. Korsakov Journal of Neurology and Psychiatry. 2024;(8):21-31

Cerebrolysin in the preventive therapy of dementia in elderly patients with mild cognitive impairment: a three-year prospective comparative study. S.S. Korsakov Journal of Neurology and Psychiatry. 2024;(9):51-59

Thrombosed aneurysm of the internal carotid artery, complicated by the development of ischemic stroke followed by subarachnoid hemorrhage. S.S. Korsakov Journal of Neurology and Psychiatry. 2024;(9):135-140

Stroke: current state of the problem. S.S. Korsakov Journal of Neurology and Psychiatry. 2024;(11):7-18

Parenteral sodium valproate and dexamethasone efficacy evaluation for alleviating migraine headache. (A randomized, controlled, double-blind study). Russian Journal of Pain. 2024;(2):10-15

Possibilities of physiotherapy in glaucomatous optic neuropathy after glaucoma surgery. Russian Annals of Ophthalmology. 2024;(3):88-94

Exogenous GalR2 receptor agonist reduces reperfusion injury in isolated rat heart. Russian Cardiology Bulletin. 2024;(3):37-42

Neurometabolic therapy with Cerebrolysin in patients with sepsis-associated encephalopathy. Russian Journal of Anesthesiology and Reanimatology. 2024;(6):46-54

Objective. To study an effect of cerebrolysin on the expression and severity of primary-generalized seizures caused by thiosemicarbazide and to analyze the corresponding molecular mechanisms.

Material and methods. The effects of cerebrolysin were studied on the thiosemicarbazide model of convulsions in 144 male rats. Cerebrolysin was introduced intraperitoneally in the dose of 2.5 ml/kg of body mass 5 days a week during 18 days.

Results and conclusion. Cerebrolysin reduces the severity and duration of seizures caused by thiosemicarbazide and increases the survival rate of animals. Cerebrolysin potentiates the anticonvulsant action of gabapentin and sodium valproate. Neurohistological analysis has shown that the thiosemicarbazide model results in the ischemic brain damage. Cerebrolysin substantially minimizes the ischemic injury of neurocytes induced by thiosemicarbazide and contributes to the restoration of brain tissue morphology.

Keywords:

seizures

ischemia

neuroprotection

neuropeptides

Cerebrolysin

gabapentin

sodium valproate

thiosemicarbazide

Authors:

Gromova O.A.

Ivanovo State Medical Academy, Ministry of Health of Russia

ORCID: 0000-0002-7663-710X

Kalacheva A.G.

Ivanovo State Medical Academy, Ministry of Health of Russia

Grishina T.R.

Ivanovo State Medical Academy, Ministry of Health of Russia, Ivanovo, Russia

Bogacheva T.E.

Ivanovo State Medical Academy, Ministry of Health of Russia, Ivanovo, Russia

Demidov V.I.

Ivanovskaia gosudarstvennaia meditsinskaia akademiia, Ivanovo

Torshin I.Yu.

Moscow Institute of Physics and Technology, Dolgoprudny

ORCID: 0000-0002-2659-7998

List of references:

Torshin IJu, Gromova OA. Jekspertnyj analiz dannyh v molekuljarnoj farmakologii. M.: MCNMO; 2012. (In Russ.).
Izhbul'dina GI. Izmenenija sistemnogo gomeostaza i svobodno-radikal'nogo okislenija lipidov v ostroj stadii ishemicheskogo insul'ta. Zhurnal nevrologii i psihiatrii im. S.S. Korsakova. 2012;112:3:31-37. (In Russ.).
Chen C, Wei S, Tsaia S, Chen X, Cho D. Cerebrolysin enhances cognitive recovery of mild traumatic brain injury patients: double-blind, placebo- controlled, randomized study. British Journal Neurosurgery. 2013;27(6) 803-807. doi: 10.3109/02688697.2013.793287.
Shamalov NA, Stahovskaja LV, Burenchev DV, Kichuk IV, Tvorogova TV, Bocyna AJu, Smychkov AS, Kerbikov OV, Mesler H, Novak P, Skvorcova VI. Vlijanie cerebrolizina v doze 50 ml na morfometricheskuju kartinu ochaga porazhenija golovnogo mozga pri ishemicheskom insul'te. Zhurnal nevrologija i psihiatrija im. S.S. Korsakova. 2010;110:12(2):34-37. (In Russ.).
Sadin AV, Zhidomorov NJu, Gogoleva IV, Demidov VI, Grishina TR, Gromova OA. Issledovanie nejroregenerativnogo dejstvija preparata Cerebrolizin pri travmaticheskom povrezhdenii golovnogo mozga. Zhurnal nevrologii i psihiatrii im. S.S. Korsakova. 2013;113(4):57-60. (In Russ.).
Vazquez-Roque R, Ubhi K, Masliah E, Flores G. Chronic cerebrolysin ad- ministration attenuates neuronal abnormalities in the basolateral amygdala induced by neonatal ventral hippocampus lesion in the rat. Synapse. 2014;68(1):31-38. doi: 10.1002/syn.21718.
Georgy G, Nassar N, Mansour H, Abdallah D. Cerebrolysin Ameloriates Cognitive Deficits in Type III Diabetic Rats. PLoSOne. 2013;8(6):64847. doi: 10.1371/journal.pone.0064847.
Gromova OA, Torshin IJu, Gogoleva IV. Peptidnyj sostav Cerebrolizina kak osnova molekuljarnyh mehanizmov dejstvija i klinicheskoj jeffektivnosti preparata. Sovremennaja terapija v psihiatrii i nevrologii. 2014;2:27-36. (In Russ.).
Gromova OA, Torshin IJu, Gogoleva IV, Pronin AV, Stel'mashuk EV, Isaev NK, Genrihs EE, Demidov VI, Volkov AJu, Haspekov GL, Aleksandrova OP. Farmakokineticheskij i farmakodinamicheskij sinergizm mezhdu nejropeptidami i litiem v realizacii nejrotroficheskogo i nejroprotektivnogo dejstvija cerebrolizina. Zhurnal nevrologii i psihiatrii im. S.S. Korsakova. 2015;3:65-72. (In Russ.). doi: 10.17116/jnevro201511531.
Gusev EI, Skvorcova VI. Ishemija golovnogo mozga. M.: Medicina; 2001. (In Russ.).
Kapur J. Galanin receptors modulate seizures. Epilepsy Currents. 2011;11(4):125-127. doi: 10.5698/1535-7511-11.4.125.
Rashid K, Van der Zee CE, Ross GM, Chapman CA, Stanisz J, Riopelle RJ, Racine RJ, Fahnestock M. A nerve growth factor peptide retards seizure development and inhibits neuronal sprouting in a rat model of epilepsy. Proceedings National Academy Sciences USA. 1995;92(21):9495-9499. doi: 10.1073/pnas.92.21.9495.
Gall C. Seizures induce dramatic and distinctly different changes in enkephalin, dynorphin, and CCK immunoreactivities in mouse hippocampal mossy fibers. Journal Neurosciences. 1988;8(6):1852-1862.
Habrieva RU. Rukovodstvo po jeksperimental'nomu (doklinicheskomu) izucheniju novyh lekarstvennyh veshhestv. M.: Medicina; 2005. (In Russ.).
Seljanina NV. Mozgovoj nejrotroficheskij faktor kak prognosticheskij kriterij razvitija kognitivnyh narushenij u bol'nyh ostroj cherepno-mozgovoj travmoj. Medicinskij al'manah. 2013;1:127-129. (In Russ.).
Seljanina NV, Karakulova JuV. Aktivacija reparativnyh processov v ostrom periode cherepno-mozgovoj travmy pod vlijaniem nejrotroficheskoj terapii. Zhurnal nevrologii i psihiatrii im. S.S. Korsakova. 2012;112(5):46-49. (In Russ.).
de Souza Bernardino TC, Teixeira AL, Miranda AS, Guidine PM, Rezende G, Doretto MC, Castro GP, Drummond L, Moraes MF, Tito PA, de Oliveira AC, Reis HJ. WistarAudiogenic Rats (WAR) exhibit altered levels of cytokines and brain-derived neurotrophic factor following audiogenic seizures. Neuroscience Letters. 2015;597:154-158. doi: 10.1016/j.neulet.2015.04.046.
Segawa M, Morinobu S, Matsumoto T, Fuchikami M, Yamawaki S. Electroconvulsive seizure, but not imipramine, rapidly up-regulates pro-BDNF and t-PA, leading to mature BDNF production, in the rat hippocampus. International Journal Neuropsychopharmacology. 2013;16(2):339-350. doi: 10.1017/S1461145712000053.
Kong S, Cheng Z, Liu J, Wang Y. Downregulated GABA and BDNF-TrkB pathway in chronic cyclothiazide seizure model. Neural Plasticity. 2014;2014:310146. doi: 10.1155/2014/310146.
Bianchin MM, Bragatti JA, Torres CM, Nuernberg GL, Rieder CR. Decreased serum BDNF levels in patients with epileptic and psychogenic nonepileptic seizures. Neurology. 2011;76(20):1772; author reply 1772-1773. doi: 10.1212/WNL.0b013e318219a086.
LaFrance WC Jr, Leaver K, Stopa EG, Papandonatos GD, Blum AS. Decreased serum BDNF levels in patients with epileptic and psychogenic nonepileptic seizures. Neurology. 2010;75(14):1285-1291. doi: 10.1212/WNL.0b013e3181f612bb.
Jacoby AS, Hort YJ, Constantinescu G, Shine J, Iismaa TP. Critical role for GALR1 galanin receptor in galanin regulation of neuroendocrine function and seizure activity. Brain Research Molecular Brain Research. 2002;107(2):195-200. doi: 10.1016/s0169-328x(02)00451-5.
Nikitidou L, Torp M, Fjord-Larsen L, Kusk P, Wahlberg LU, Kokaia M. Encapsulated galanin-producing cells attenuate focal epileptic seizures in the hippocampus. Epilepsia. 2014;55(1):167-174. doi: 10.1111/epi.12470.
Kanter-Schlifke I, Toft Sorensen A, Ledri M, Kuteeva E, Hokfelt T, Kokaia M. Galanin gene transfer curtails generalized seizures in kindled rats without altering hippocampal synaptic plasticity. Neuroscience. 2007;150(4):984-992. doi: 10.1016/j.neuroscience.2007.09.056.
McCown TJ. Adeno-associated virus vector-mediated expression and constitutive secretion of galanin suppresses limbic seizure activity. Neurotherapeutics. 2009;6(2):307-311. doi: 10.1016/j.nurt.2009.01.004.
Mazarati AM, Halaszi E, Telegdy G. Anticonvulsive effects of galanin administered into the central nervous system upon the picrotoxin-kindled seizure syndrome in rats. Brain Research. 1992;589(1):164-166. doi: 10.1016/0006-8993(92)91179-i.
Rajput SK, Singh JN, Ingole S, Jain G, Kaur N, Monga V, Meena CL, Jain R, Sharma SS. Neuropharmacological profile of L-pGlu-(1-benzyl)-L-His-L-ProNH2, a newer thyrotropin-releasing hormone analog: effects on seizure models, sodium current, cerebral blood flow and behavioral parameters. Epilepsy Research. 2009;87(2-3):223-233. doi: 10.1016/j.eplepsyres.2009.09.007.
Kandratavicius L, Hallak JE, Carlotti CG, Assirati JA Jr, Leite JP. Neurotrophinreceptors expression in mesial temporal lobe epilepsy with and without psychiatric comorbidities and their relation with seizure type and surgical outcome. Acta Neuropathologica Communications. 2014;2:81. doi: 10.1186/s40478-014-0081-2.
Ubhi K, Rockenstein E, Vazquez-Roque R, Mante M, Inglis C, Patrick C, Adame A, Fahnestock M, Doppler E, Novak P, Moessler H, Masliah E. Cerebrolysin modulates pronerve growth factor/nerve growth factor ratio and ameliorates the cholinergic deficit in a transgenic model of Alzheimer's disease. Journal Neuroscience Research. 2013;91(2):167-177. doi: 10.1002/jnr.23142.
Somera-Molina KC, Nair S, Van Eldik LJ, Watterson DM, Wainwright MS. Enhanced microglial activation and proinflammatory cytokine upregulation are linked to increased susceptibility to seizures and neurologic injury in a 'two-hit' seizure model. Brain Research. 2009;1282:162-172. doi: 10.1016/j.brainres.2009.05.073.
Paradiso B, Zucchini S, Su T, Bovolenta R, Berto E, Marconi P, Marzola A, Navarro Mora G, Fabene PF, Simonato M. Localized overexpression of FGF-2 and BDNF in hippocampus reduces mossy fiber sprouting and spontaneous seizures up to 4 weeks after pilocarpine-induced status epilepticus. Epilepsia. 2011;52(3):572-578. doi: 10.1111/j.1528-1167.2010.02930.x.
Bovolenta R, Zucchini S, Paradiso B, Rodi D, Merigo F, Navarro Mora G, Osculati F, Berto E, Marconi P, Marzola A, Fabene PF, Simonato M. Hippocampal FGF-2 and BDNF overexpression attenuates epileptogenesis-associated neuroinflammation and reduces spontaneous recurrent seizures. Journal Neuroinflammation. 2010;7:81. doi: 10.1186/1742-2094-7-81.
Serkina EV, Gromova OA, Torshin IJu, Sotnikova NYU, Nikonov A.A. Cerebrolizin oblegchaet sostojanie bol'nyh s perinatal'nym porazheniem CNS cherez moduljaciju autoimmuniteta i antioksidantnuju zashhitu. Zhurnal nevrologii i psihiatrii im. S.S. Korsakova. 2008;108(11):62-66. (In Russ.).

Close metadata