Влияние кардарина на экспрессию генов белков, вовлеченных в эпилептогенез, в гиппокампе крыс в литий-пилокарпиновой модели височной эпилепсии

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В последние годы активно обсуждается роль в патогенезе эпилепсии астро- и микроглиальных клеток и связанного с ними нейровоспаления. Эти клетки могут быть в разных функциональных состояниях, крайние из которых A1 и M1 фенотипы продуцируют преимущественно провоспалительные (способствующие эпилептогенезу) белки, а A2 и M2 фенотипы – противовоспалительные (предотвращающие эпилептогенез) белки. Предполагается, что использование препаратов, способных стимулировать поляризацию от М1 и А1 к М2 и А2 фенотипам, может стать успешной стратегией лечения эпилепсии. К таким препаратам относятся агонисты ядерных рецепторов, активируемых пролифератором пероксисом (PPARs). Целью данной работы стало изучение изменений экспрессии микро- и астроглиальных белков, вовлеченных в регуляцию эпилептогенеза, в дорзальном гиппокампе крыс в литий-пилокарпиновой модели височной эпилепсии и исследование влияния на эти процессы агониста PPAR бета/дельта кардарина. Кардарин вводили на начальных этапах эпилептогенеза (в течение 7 дней после индукции TLE модели), через два месяца (хроническая фаза модели) проводили анализ экспрессии генов интереса в дорзальном гиппокампе методом ОТ-ПЦР в реальном времени. Проведенное исследование выявило изменение экспрессии генов астро- и микроглиальных белков в процессе эпилептогенеза, в основном связанное с усилением нейровоспалительных процессов и ослаблением нейропротекторных свойств этих клеток. У TLE крыс увеличивалась экспрессия генов маркеров активации астро- (Gfap) и микроглии (Aif1), про- (Il1b, Nlrp3) и противовоспалительных (Il1rn) белков, маркеров фенотипа A1 астроцитов (Lcn2, Gbp2) и ростовых факторов (Bdnf, Fgf2). Экспрессия гена защитного М2 фенотипа Arg1 снижалась у TLE крыс. Наиболее яркий эффект введения кардарина проявился в усилении экспрессии гена маркера A2 фенотипа астроцитов S100a10.

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А. Р. Харисова

Институт эволюционной физиологии и биохимии им. И. М. Сеченова РАН

Email: ZubarevaOE@mail.ru
Россия, Санкт-Петербург

А. И. Рогинская

Институт эволюционной физиологии и биохимии им. И. М. Сеченова РАН

Email: ZubarevaOE@mail.ru
Россия, Санкт-Петербург

О. Е. Зубарева

Институт эволюционной физиологии и биохимии им. И. М. Сеченова РАН

Автор, ответственный за переписку.
Email: ZubarevaOE@mail.ru
Россия, Санкт-Петербург

Список литературы

  1. Fiest KM, Sauro KM, Wiebe S, Patten SB, Kwon C-S, Dykeman J, Pringsheim T, Lorenzetti DL, Jetté N (2017) Prevalence and incidence of epilepsy. Neurology 88: 296–303. https://doi.org/10.1212/WNL.0000000000003509
  2. Löscher W, Klitgaard H, Twyman RE, Schmidt D (2013) New avenues for anti-epileptic drug discovery and development. Nat Rev Drug Discov 12: 757–776. https://doi.org/10.1038/nrd4126
  3. Soltani Khaboushan A, Yazdanpanah N, Rezaei N (2022) Neuroinflammation and Proinflammatory Cytokines in Epileptogenesis. Mol Neurobiol 59: 1724–1743. https://doi.org/10.1007/s12035–022–02725–6
  4. Chen B, Choi H, Hirsch LJ, Katz A, Legge A, Buchsbaum R, Detyniecki K (2017) Psychiatric and behavioral side effects of antiepileptic drugs in adults with epilepsy. Epilepsy Behav 76: 24–31. https://doi.org/10.1016/j.yebeh.2017.08.039
  5. Akyuz E, Polat AK, Eroglu E, Kullu I, Angelopoulou E, Paudel YN (2021) Revisiting the role of neurotransmitters in epilepsy: An updated review. Life Sci 265: 118826. https://doi.org/10.1016/j.lfs.2020.118826
  6. Boison D, Steinhäuser C (2018) Epilepsy and astrocyte energy metabolism. Glia 66: 1235–1243. https://doi.org/10.1002/glia.23247
  7. Pracucci E, Pillai V, Lamers D, Parra R, Landi S (2021) Neuroinflammation: A Signature or a Cause of Epilepsy? Int J Mol Sci 22: 6981. https://doi.org/10.3390/ijms22136981
  8. Dyomina AV, Zubareva OE, Smolensky IV, Vasilev DS, Zakharova MV, Kovalenko AA, Schwarz AP, Ischenko AM, Zaitsev AV (2020) Anakinra Reduces Epileptogenesis, Provides Neuroprotection, and Attenuates Behavioral Impairments in Rats in the Lithium-Pilocarpine Model of Epilepsy. Pharmaceuticals (Basel) 13: 340. https://doi.org/10.3390/ph13110340
  9. Dubé C, Vezzani A, Behrens M, Bartfai T, Baram TZ (2005) Interleukin-1beta contributes to the generation of experimental febrile seizures. Ann Neurol 57: 152–155. https://doi.org/10.1002/ana.20358
  10. Kwon HS, Koh S-H (2020) Neuroinflammation in neurodegenerative disorders: the roles of microglia and astrocytes. Transl Neurodegener 9: 42. https://doi.org/10.1186/s40035–020–00221–2
  11. Deng X-L, Feng L, Wang Z-X, Zhao Y-E, Zhan Q, Wu X-M, Xiao B, Shu Y (2020) The Runx1/Notch1 Signaling Pathway Participates in M1/M2 Microglia Polarization in a Mouse Model of Temporal Lobe Epilepsy and in BV-2 Cells. Neurochem Res 45: 2204–2216. https://doi.org/10.1007/s11064–020–03082–3
  12. Fan Y-Y, Huo J (2021) A1/A2 astrocytes in central nervous system injuries and diseases: Angels or devils? Neurochem Int 148: 105080. https://doi.org/10.1016/j.neuint.2021.105080
  13. Hong F, Pan S, Guo Y, Xu P, Zhai Y (2019) PPARs as Nuclear Receptors for Nutrient and Energy Metabolism. Molecules 24: 2545. https://doi.org/10.3390/molecules24142545
  14. Ji J, Xue T-F, Guo X-D, Yang J, Guo R-B, Wang J, Huang J-Y, Zhao X-J, Sun X-L (2018) Antagonizing peroxisome proliferator-activated receptor γ facilitates M1-to-M2 shift of microglia by enhancing autophagy via the LKB1-AMPK signaling pathway. Aging Cell 17: e12774. https://doi.org/10.1111/acel.12774
  15. Krémarik-Bouillaud P, Schohn H, Dauça M (2000) Regional distribution of PPARβ in the cerebellum of the rat. J Chem Neuroanat 19: 225–232. https://doi.org/10.1016/S0891–0618(00)00065-X
  16. Granneman J, Skoff R, Yang X (1998) Member of the peroxisome proliferator-activated receptor family of transcription factors is differentially expressed by oligodendrocytes. J Neurosci Res 51: 563–573. https://doi.org/10.1002/(SICI)1097–4547(19980301)51:5<563:: AID-JNR3>3.0.CO;2-D
  17. Bernardo A, Ajmone-Cat MA, Levi G, Minghetti L (2003) 15-deoxy-delta12,14-prostaglandin J2 regulates the functional state and the survival of microglial cells through multiple molecular mechanisms. J Neurochem 87: 742–751. https://doi.org/10.1046/j.1471–4159.2003.02045.x
  18. Cristiano L, Bernardo A, Cerù MP (2001) Peroxisome proliferator-activated receptors (PPARs) and peroxisomes in rat cortical and cerebellar astrocytes. J Neurocytol 30: 671–683. https://doi.org/10.1023/A:1016525716209
  19. Grygiel-Górniak B (2014) Peroxisome proliferator-activated receptors and their ligands: nutritional and clinical implications – a review. Nutr J 13: 17. https://doi.org/10.1186/1475–2891–13–17
  20. Knowles S, Budney S, Deodhar M, Matthews SA, Simeone KA, Simeone TA (2018) Ketogenic diet regulates the antioxidant catalase via the transcription factor PPARγ2. Epilepsy Res 147: 71–74. https://doi.org/10.1016/j.eplepsyres.2018.09.009
  21. Senn L, Costa A-M, Avallone R, Socała K, Wlaź P, Biagini G (2023) Is the peroxisome proliferator-activated receptor gamma a putative target for epilepsy treatment? Current evidence and future perspectives. Pharmacol Ther 241: 108316. https://doi.org/10.1016/j.pharmthera.2022.108316
  22. Pérez-Segura I, Santiago-Balmaseda A, Rodríguez-Hernández LD, Morales-Martínez A, Martínez-Becerril HA, Martínez-Gómez PA, Delgado-Minjares KM, Salinas-Lara C, Martínez-Dávila IA, Guerra-Crespo M, Pérez-Severiano F, Soto-Rojas LO (2023) PPARs and Their Neuroprotective Effects in Parkinson’s Disease: A Novel Therapeutic Approach in α-Synucleinopathy? Int J Mol Sci 24: 3264. https://doi.org/10.3390/ijms24043264
  23. Adabi Mohazab R, Javadi-Paydar M, Delfan B, Dehpour AR (2012) Possible involvement of PPAR-gamma receptor and nitric oxide pathway in the anticonvulsant effect of acute pioglitazone on pentylenetetrazole-induced seizures in mice. Epilepsy Res 101: 28–35. https://doi.org/10.1016/j.eplepsyres.2012.02.015
  24. Yu X, Shao X-G, Sun H, Li Y-N, Yang J, Deng Y-C, Huang Y-G (2008) Activation of cerebral peroxisome proliferator-activated receptors gamma exerts neuroprotection by inhibiting oxidative stress following pilocarpine-induced status epilepticus. Brain Res 1200: 146–158. https://doi.org/10.1016/j.brainres.2008.01.047
  25. Peng J, Wang K, Xiang W, Li Y, Hao Y, Guan Y (2019) Rosiglitazone polarizes microglia and protects against pilocarpine-induced status epilepticus. CNS Neurosci Ther 25: 1363–1372. https://doi.org/10.1111/cns.13265
  26. Tang X, Yan K, Wang Y, Wang Y, Chen H, Xu J, Lu Y, Wang X, Liang J, Zhang X (2020) Activation of PPAR-β/δ Attenuates Brain Injury by Suppressing Inflammation and Apoptosis in a Collagenase-Induced Intracerebral Hemorrhage Mouse Model. Neurochem Res 45: 837–850. https://doi.org/10.1007/s11064–020–02956-w
  27. Ahmed Juvale II, Che Has AT (2020) The evolution of the pilocarpine animal model of status epilepticus. Heliyon 6: e04557. https://doi.org/10.1016/j.heliyon.2020.e04557
  28. Curia G, Lucchi C, Vinet J, Gualtieri F, Marinelli C, Torsello A, Costantino L, Biagini G (2014) Pathophysiogenesis of mesial temporal lobe epilepsy: is prevention of damage antiepileptogenic? Current Med Chem 21: 663–688. https://doi.org/10.2174/0929867320666131119152201
  29. Bojja SL, Singh N, Kolathur KK, Rao CM (2022) What is the Role of Lithium in Epilepsy? Curr Neuropharmacol 20: 1850–1864. https://doi.org/10.2174/1570159X20666220411081728
  30. Furtado MA, Castro OW, Vecchio FD, Oliveira JAC de, Garcia-Cairasco N (2011) Study of spontaneous recurrent seizures and morphological alterations after status epilepticus induced by intrahippocampal injection of pilocarpine. Epilepsy and Behavior 20: 257–266. https://doi.org/10.1016/j.yebeh.2010.11.024
  31. Paxinos G, Watson C (2007) The rat brain in stereotaxic coordinates. 6th ed. Elsevier/Acad Press. Amsterdam, Boston.
  32. Dubey V, Roy A, Dixit AB, Tripathi M, Pandey S, Jain S, Chandra PS, Banerjee J (2023) Dendritic reorganization in the hippocampus, anterior temporal lobe, and frontal neocortex of lithium-pilocarpine induced Status Epilepticus (SE). J Chem Neuroanat 133: 102329. https://doi.org/10.1016/j.jchemneu.2023.102329
  33. Jurga AM, Paleczna M, Kadluczka J, Kuter KZ (2021) Beyond the GFAP-Astrocyte Protein Markers in the Brain. Biomolecules 11: 1361. https://doi.org/10.3390/biom11091361
  34. Jurga AM, Paleczna M, Kuter KZ (2020) Overview of General and Discriminating Markers of Differential Microglia Phenotypes. Front Cell Neurosci 14: 198. https://doi.org/10.3389/fncel.2020.00198
  35. Wu C, Zhang G, Chen L, Kim S, Yu J, Hu G, Chen J, Huang Y, Zheng G, Huang S (2019) The Role of NLRP3 and IL-1β in Refractory Epilepsy Brain Injury. Front Neurol 10: 1418. https://doi.org/10.3389/fneur.2019.01418
  36. Shin HJ, Jeong EA, Lee JY, An HS, Jang HM, Ahn YJ, Lee J, Kim KE, Roh GS (2021) Lipocalin-2 Deficiency Reduces Oxidative Stress and Neuroinflammation and Results in Attenuation of Kainic Acid-Induced Hippocampal Cell Death. Antioxidants 10: 100. https://doi.org/10.3390/antiox10010100
  37. Sharma S, Puttachary S, Thippeswamy T (2019) Glial source of nitric oxide in epileptogenesis: A target for disease modification in epilepsy. J Neurosci Res 97: 1363–1377. https://doi.org/10.1002/jnr.24205
  38. Munder M (2009) Arginase: an emerging key player in the mammalian immune system. Br J Pharmacol 158: 638–651. https://doi.org/10.1111/j.1476–5381.2009.00291.x
  39. Cherry JD, Olschowka JA, O’Banion MK (2014) Neuroinflammation and M2 microglia: the good, the bad, and the inflamed. J Neuroinflammat 11: 98. https://doi.org/10.1186/1742–2094–11–98
  40. Simonato M (2014) Gene therapy for epilepsy. Epilepsy Behav 38: 125–130. https://doi.org/10.1016/j.yebeh.2013.09.013
  41. AlRuwaili R, Al-Kuraishy HM, Al-Gareeb AI, Ali NH, Alexiou A, Papadakis M, Saad HM, Batiha GE-S (2024) The Possible Role of Brain-derived Neurotrophic Factor in Epilepsy. Neurochem Res 49: 533–547. https://doi.org/10.1007/s11064–023–04064-x
  42. Chiavellini P, Canatelli-Mallat M, Lehmann M, Goya RG, Morel GR (2022) Therapeutic potential of glial cell line-derived neurotrophic factor and cell reprogramming for hippocampal-related neurological disorders. Neural Regen Res 17: 469–476. https://doi.org/10.4103/1673–5374.320966
  43. Livak KJ, Schmittgen TD (2001) Analysis of relative gene expression data using real-time quantitative PCR and the 2-ΔΔCT method. Methods 25: 402–408. https://doi.org/10.1006/meth.2001.1262
  44. Schwarz AP, Malygina DA, Kovalenko AA, Trofimov AN, Zaitsev AV (2020) Multiplex qPCR assay for assessment of reference gene expression stability in rat tissues/samples. Mol Cell Probes 53: 101611. https://doi.org/10.1016/j.mcp.2020.101611
  45. Bonefeld BE, Elfving B, Wegener G (2008) Reference genes for normalization: a study of rat brain tissue. Synapse 62: 302–309. https://doi.org/10.1002/syn.20496
  46. Lin W, Burks CA, Hansen DR, Kinnamon SC, Gilbertson TA (2004) Taste receptor cells express pH-sensitive leak K+ channels. J Neurophysiol 92: 2909–2919. https://doi.org/10.1152/jn.01198.2003
  47. Yamaguchi M, Yamauchi A, Nishimura M, Ueda N, Naito S (2005) Soybean oil fat emulsion prevents cytochrome P450 mRNA down-regulation induced by fat-free overdose total parenteral nutrition in infant rats. Biol Pharm Bull 28: 143–147. https://doi.org/10.1248/bpb.28.143
  48. Swijsen A, Nelissen K, Janssen D, Rigo J-M, Hoogland G (2012) Validation of reference genes for quantitative real-time PCR studies in the dentate gyrus after experimental febrile seizures. BMC Res Notes 5: 685. https://doi.org/10.1186/1756–0500–5–685
  49. Pohjanvirta R, Niittynen M, Lindén J, Boutros PC, Moffat ID, Okey AB (2006) Evaluation of various housekeeping genes for their applicability for normalization of mRNA expression in dioxin-treated rats. Chem Biol Interact 160: 134–149. https://doi.org/10.1016/j.cbi.2006.01.001
  50. Langnaese K, John R, Schweizer H, Ebmeyer U, Keilhoff G (2008) Selection of reference genes for quantitative real-time PCR in a rat asphyxial cardiac arrest model. BMC Mol Biol 9: 53. https://doi.org/10.1186/1471–2199–9–53
  51. Rioja I, Bush KA, Buckton JB, Dickson MC, Life PF (2004) Joint cytokine quantification in two rodent arthritis models: kinetics of expression, correlation of mRNA and protein levels and response to prednisolone treatment. Clin Exp Immunol 137: 65–73. https://doi.org/10.1111/j.1365–2249.2004.02499.x
  52. Zubareva OE, Dyomina AV, Kovalenko AA, Roginskaya AI, Melik-Kasumov TB, Korneeva MA, Chuprina AV, Zhabinskaya AA, Kolyhan SA, Zakharova MV, Gryaznova MO, Zaitsev AV (2023) Beneficial Effects of Probiotic Bifidobacterium longum in a Lithium-Pilocarpine Model of Temporal Lobe Epilepsy in Rats. Int J Mol Sci 24: 8451. https://doi.org/10.3390/ijms24098451
  53. Su J-C, Zhang Y, Cheng C, Zhu Y-N, Ye Y-M, Sun Y-K, Xiang S-Y, Wang Y, Liu Z-B, Zhang X-F (2021) Hydrogen regulates the M1/M2 polarization of alveolar macrophages in a rat model of chronic obstructive pulmonary disease. Exp Lung Res 47: 301–310. https://doi.org/10.1080/01902148.2021.1919788
  54. Sang N, Yun Y, Li H, Hou L, Han M, Li G (2010) SO2 inhalation contributes to the development and progression of ischemic stroke in the brain. Toxicol Sci 114: 226–236. https://doi.org/10.1093/toxsci/kfq010
  55. Cernecka H, Doka G, Srankova J, Pivackova L, Malikova E, Galkova K, Kyselovic J, Krenek P, Klimas J (2016) Ramipril restores PPARβ/δ and PPARγ expressions and reduces cardiac NADPH oxidase but fails to restore cardiac function and accompanied myosin heavy chain ratio shift in severe anthracycline-induced cardiomyopathy in rat. Eur J Pharmacol 791: 244–253. https://doi.org/10.1016/j.ejphar.2016.08.040
  56. Chistyakov DV, Aleshin SE, Astakhova AA, Sergeeva MG, Reiser G (2015) Regulation of peroxisome proliferator-activated receptors (PPAR) α and -γ of rat brain astrocytes in the course of activation by toll-like receptor agonists. J Neurochem 134: 113–124. https://doi.org/10.1111/jnc.13101
  57. Johnson AM, Sugo E, Barreto D, Hiew C-C, Lawson JA, Connolly AM, Somerville E, Hasic E, Bye AM, Cunningham AM (2016) The Severity of Gliosis in Hippocampal Sclerosis Correlates with Pre-Operative Seizure Burden and Outcome After Temporal Lobectomy. Mol Neurobiol 53: 5446–5456. https://doi.org/10.1007/s12035–015–9465-y
  58. Rath M, Müller I, Kropf P, Closs EI, Munder M (2014) Metabolism via Arginase or Nitric Oxide Synthase: Two Competing Arginine Pathways in Macrophages. Front Immunol 5: 532. https://doi.org/10.3389/fimmu.2014.00532
  59. Subkhankulov MR, Sinyak DS, Guk VA, Postnikova TYu, Roginskaya AI, Zubareva OE (2024) Cardarin Effect on the Formation of Histopathological and Behavioral Abnormalities in the Lithium-Pilocarpine Model of Temporal Lobe Epilepsy in Rats. J Evol Biochem Phys 60: 316–331. https://doi.org/10.1134/S002209302401023X
  60. Xu Z, Xue T, Zhang Z, Wang X, Xu P, Zhang J, Lei X, Li Y, Xie Y, Wang L, Fang M, Chen Y (2011) Role of signal transducer and activator of transcription-3 in up-regulation of GFAP after epilepsy. Neurochem Res 36: 2208–2215. https://doi.org/10.1007/s11064–011–0576–1
  61. Flores-Cuadrado A, Saiz-Sanchez D, Mohedano-Moriano A, Lamas-Cenjor E, Leon-Olmo V, Martinez-Marcos A, Ubeda-Bañon I (2021) Astrogliosis and sexually dimorphic neurodegeneration and microgliosis in the olfactory bulb in Parkinson’s disease. NPJ Parkinsons Dis 7: 11. https://doi.org/10.1038/s41531–020–00154–7
  62. Kandratavicius L, Peixoto-Santos JE, Monteiro MR, Scandiuzzi RC, Carlotti CG, Assirati JA, Hallak JE, Leite JP (2015) Mesial temporal lobe epilepsy with psychiatric comorbidities: a place for differential neuroinflammatory interplay. J Neuroinflammat 12: 38. https://doi.org/10.1186/s12974–015–0266-z
  63. Kyriatzis G, Bernard A, Bôle A, Khrestchatisky M, Ferhat L (2024) In the Rat Hippocampus, Pilocarpine-Induced Status Epilepticus Is Associated with Reactive Glia and Concomitant Increased Expression of CD31, PDGFRβ, and Collagen IV in Endothelial Cells and Pericytes of the Blood-Brain Barrier. Int J Mol Sci 25: 1693. https://doi.org/10.3390/ijms25031693
  64. Robel S, Sontheimer H (2016) Glia as drivers of abnormal neuronal activity. Nat Neurosci 19: 28–33. https://doi.org/10.1038/nn.4184
  65. Robel S (2017) Astroglial Scarring and Seizures: A Cell Biological Perspective on Epilepsy. Neuroscientist 23: 152–168. https://doi.org/10.1177/1073858416645498
  66. Rana A, Musto AE (2018) The role of inflammation in the development of epilepsy. J Neuroinflammat 15: 144. https://doi.org/10.1186/s12974–018–1192–7
  67. Pohlentz MS, Müller P, Cases-Cunillera S, Opitz T, Surges R, Hamed M, Vatter H, Schoch S, Becker AJ, Pitsch J (2022) Characterisation of NLRP3 pathway-related neuroinflammation in temporal lobe epilepsy. PLoS One 17: e0271995. https://doi.org/10.1371/journal.pone.0271995
  68. Defaux A, Zurich M-G, Braissant O, Honegger P, Monnet-Tschudi F (2009) Effects of the PPAR-beta agonist GW501516 in an in vitro model of brain inflammation and antibody-induced demyelination. J Neuroinflammat 6: 15. https://doi.org/10.1186/1742–2094–6–15
  69. Alese OO, Mabandla MV (2019) Upregulation of hippocampal synaptophysin, GFAP and mGluR3 in a pilocarpine rat model of epilepsy with history of prolonged febrile seizure. J Chem Neuroanat 100: 101659. https://doi.org/10.1016/j.jchemneu.2019.101659
  70. Dahal A, Govindarajan K, Kar S (2023) Administration of Kainic Acid Differentially Alters Astrocyte Markers and Transiently Enhanced Phospho-tau Level in Adult Rat Hippocampus. Neuroscience 516: 27–41. https://doi.org/10.1016/j.neuroscience.2023.02.010
  71. Fei X, Dou Y-N, Wang L, Wu X, Huan Y, Wu S, He X, Lv W, Wei J, Fei Z (2022) Homer1 promotes the conversion of A1 astrocytes to A2 astrocytes and improves the recovery of transgenic mice after intracerebral hemorrhage. J Neuroinflammat 19: 67. https://doi.org/10.1186/s12974–022–02428–8
  72. Milosevic A, Liebmann T, Knudsen M, Schintu N, Svenningsson P, Greengard P (2017) Cell- and region-specific expression of depression-related protein p11 (S100a10) in the brain. J Comp Neurol 525:955–975. https://doi.org/10.1002/cne.24113
  73. Ogweno G, Murungi E (2023) Evolving Paradigms in Laboratory Biomarkers of Fibrinolysis Phenotypes and Association with Post-Traumatic Vascular Thrombosis. In book: Advances in the Diagnosis and Management of Vascular Thrombosis. IntechOpen. https://doi.org/10.5772/intechopen.111678
  74. Okura G, Bharadwaj A, Waisman Dm (2023) Recent Advances in Molecular and Cellular Functions of S100A10. Biomolecules 13(10): 1450. https://doi.org/10.3390/biom13101450
  75. Svenningsson Per, Kim K, Warner-Schmidt J, Oh Y, Greengard P (2013) p11 and its role in depression and therapeutic responses to antidepressants. Nature Rev Neurosci 14(10): 673–680. https://doi.org/10.1038/nrn3564
  76. Yamagata K, Hakata K, Maeda A, Mochizuki C, Matsufuji H, Chino M, Yamori Y (2007) Adenosine induces expression of glial cell line-derived neurotrophic factor (GDNF) in primary rat astrocytes. Neurosci Res 59: 467–474. https://doi.org/10.1016/j.neures.2007.08.016
  77. Fahmy GH, Moftah MZ (2010) FGF-2 in Astroglial Cells During Vertebrate Spinal Cord Recovery. Front Cell Neurosci 4. https://doi.org/10.3389/fncel.2010.00129
  78. Ferrini F, De Koninck Y (2013) Microglia Control Neuronal Network Excitability via BDNF Signalling. Neural Plasticity 2013: e429815. https://doi.org/10.1155/2013/429815
  79. Martínez-Levy GA, Rocha L, Rodríguez-Pineda F, Alonso-Vanegas MA, Nani A, Buentello-García RM, Briones-Velasco M, San-Juan D, Cienfuegos J, Cruz-Fuentes CS (2018) Increased Expression of Brain-Derived Neurotrophic Factor Transcripts I and VI, cAMP Response Element Binding, and Glucocorticoid Receptor in the Cortex of Patients with Temporal Lobe Epilepsy. Mol Neurobiol 55: 3698–3708. https://doi.org/10.1007/s12035–017–0597–0
  80. Schmidt-Kastner R, Humpel C, Wetmore C, Olson L (1996) Cellular hybridization for BDNF, trkB, and NGF mRNAs and BDNF-immunoreactivity in rat forebrain after pilocarpine-induced status epilepticus. Exp Brain Res 107: 331–347. https://doi.org/10.1007/BF00230416
  81. Gliwińska A, Czubilińska-Łada J, Więckiewicz G, Świętochowska E, Badeński A, Dworak M, Szczepańska M (2023) The Role of Brain-Derived Neurotrophic Factor (BDNF) in Diagnosis and Treatment of Epilepsy, Depression, Schizophrenia, Anorexia Nervosa and Alzheimer’s Disease as Highly Drug-Resistant Diseases: A Narrative Review. Brain Sci 13: 163. https://doi.org/10.3390/brainsci13020163
  82. Cunha C, Brambilla R, Thomas KL (2010) A simple role for BDNF in learning and memory? Front Mol Neurosci 3: 1. https://doi.org/10.3389/neuro.02.001.2010
  83. Gibon J, Buckley SM, Unsain N, Kaartinen V, Séguéla P, Barker PA (2015) proBDNF and p75NTR Control Excitability and Persistent Firing of Cortical Pyramidal Neurons. J Neurosci 35: 9741–9753. https://doi.org/10.1523/JNEUROSCI.4655–14.2015
  84. Scharfman HE, Goodman JH, Sollas AL, Croll SD (2002) Spontaneous limbic seizures after intrahippocampal infusion of brain-derived neurotrophic factor. Exp Neurol 174: 201–214. https://doi.org/10.1006/exnr.2002.7869
  85. Kanter-Schlifke I, Georgievska B, Kirik D, Kokaia M (2007) Seizure suppression by GDNF gene therapy in animal models of epilepsy. Mol Ther 15: 1106–1113. https://doi.org/10.1038/sj.mt.6300148
  86. Humpel C, Hoffer B, Strömberg I, Bektesh S, Collins F, Olson L (1994) Neurons of the hippocampal formation express glial cell line-derived neurotrophic factor messenger RNA in response to kainate-induced excitation. Neuroscience 59: 791–795. https://doi.org/10.1016/0306–4522(94)90284–4
  87. Schmidt-Kastner R, Tomac A, Hoffer B, Bektesh S, Rosenzweig B, Olson L (1994) Glial cell-line derived neurotrophic factor (GDNF) mRNA upregulation in striatum and cortical areas after pilocarpine-induced status epilepticus in rats. Brain Res Mol Brain Res 26: 325–330. https://doi.org/10.1016/0169–328x(94)90106–6
  88. Woodbury ME, Ikezu T (2014) Fibroblast growth factor-2 signaling in neurogenesis and neurodegeneration. J Neuroimmun Pharmacol 9: 92–101. https://doi.org/10.1007/s11481–013–9501–5
  89. Postnikova TY, Diespirov GP, Amakhin DV, Vylekzhanina EN, Soboleva EB, Zaitsev AV (2021) Impairments of Long-Term Synaptic Plasticity in the Hippocampus of Young Rats during the Latent Phase of the Lithium-Pilocarpine Model of Temporal Lobe Epilepsy. Int J Mol Sci 22: 13355. https://doi.org/10.3390/ijms222413355
  90. Paradiso B, Zucchini S, Simonato M (2013) Implication of fibroblast growth factors in epileptogenesis-associated circuit rearrangements. Front Cell Neurosci 7: 152. https://doi.org/10.3389/fncel.2013.00152
  91. Liu Z, Holmes GL (1997) Basic fibroblast growth factor-induced seizures in rats. Neurosci Lett 233: 85–88. https://doi.org/10.1016/s0304–3940(97)00627–7
  92. Liu Z, D’Amore PA, Mikati M, Gatt A, Holmes GL (1993) Neuroprotective effect of chronic infusion of basic fibroblast growth factor on seizure-associated hippocampal damage. Brain Res 626: 335–338. https://doi.org/10.1016/0006–8993(93)90598-h
  93. Esmaeili MA, Yadav S, Gupta RKr, Waggoner GR, Deloach A, Calingasan NY, Beal MF, Kiaei M (2016) Preferential PPAR-α activation reduces neuroinflammation, and blocks neurodegeneration in vivo. Hum Mol Genet 25: 317–327. https://doi.org/10.1093/hmg/ddv477
  94. Ibáñez C, Acuña T, Quintanilla ME, Pérez-Reytor D, Morales P, Karahanian E (2023) Fenofibrate Decreases Ethanol-Induced Neuroinflammation and Oxidative Stress and Reduces Alcohol Relapse in Rats by a PPAR-α-Dependent Mechanism. Antioxidants (Basel) 12: 1758. https://doi.org/10.3390/antiox12091758
  95. Puligheddu M, Pillolla G, Melis M, Lecca S, Marrosu F, De Montis MG, Scheggi S, Carta G, Murru E, Aroni S, Muntoni AL, Pistis M (2013) PPAR-alpha agonists as novel antiepileptic drugs: preclinical findings. PLoS One 8: e64541. https://doi.org/10.1371/journal.pone.0064541
  96. Puligheddu M, Melis M, Pillolla G, Milioli G, Parrino L, Terzano GM, Aroni S, Sagheddu C, Marrosu F, Pistis M, Muntoni AL (2017) Rationale for an adjunctive therapy with fenofibrate in pharmacoresistant nocturnal frontal lobe epilepsy. Epilepsia 58: 1762–1770. https://doi.org/10.1111/epi.13863

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2. Рис. 1. Схема эксперимента. Cntr+Veh – контрольная группа без введения кардарина; TLE+Veh – экспериментальная группа без введения кардарина; Cntr+GW – контрольная группа с введением кардарина; TLE+GW – экспериментальная группа с введением кардарина. На срезе мозга представлена схема выделения дорзального гиппокампа.

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3. Рис. 2. Относительная экспрессия генов маркера активации астроцитов Gfap (a) и микроглиальных клеток Aif1 (b) в дорзальном гиппокампе экспериментальных и контрольных крыс; * р < 0.05, двухфакторный ANOVA (модель х лечение) с апостериорным тестом множественных сравнений Сидака или непараметрический аналог ANOVA тест Крускала – Уоллиса с апостериорным тестом множественных сравнений Данна.

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4. Рис. 3. Относительная экспрессия генов провоспалительных белков Il1b (a), Nlrp3 (b), Tnfa (d) и противовоспалительного цитокина Il1rn (с) в дорзальном гиппокампе экспериментальных и контрольных крыс; * р < 0.05, ** p < 0.01, двухфакторный ANOVA (модель х лечение) с апостериорным тестом множественных сравнений Сидака или непараметрический аналог ANOVA тест Крускала – Уоллиса с апостериорным тестом множественных сравнений Данна.

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5. Рис. 4. Относительная экспрессия генов маркеров провоспалительного А1 фенотипа (a, b) и нейропротекторного фенотипа А2 (с, d) астроглии в дорзальном гиппокампе экспериментальных и контрольных крыс; * р < 0.05, ** p < 0.01, двухфакторный ANOVA (модель х лечение) с апостериорным тестом множественных сравнений Сидака.

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6. Рис. 5. Относительная экспрессия генов маркеров провоспалительного М1 (a) и противовоспалительного М2 (b) фенотипа микроглии, а также их соотношение (c) в дорзальном гиппокампе экспериментальных и контрольных крыс. * р < 0.05 в двухфакторном ANOVA (модель х лечение) с апостериорным тестом множественных сравнений Сидака.

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7. Рис. 6. Относительная экспрессия генов нейротрофических факторов Bdnf (a), Gdnf (b) и Fgf2 (с) в дорзальном гиппокампе крыс; * р < 0.05; двухфакторный ANOVA (модель х лечение) с апостериорным тестом множественных сравнений Сидака.

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8. Рис. 7. Относительная экспрессия генов PPARs: Ppara (a), Ppard (b), Pparg (c) в дорзальном гиппокампе крыс; двухфакторный ANOVA (модель х лечение).

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