ИЗМЕНЕНИЯ СИНАПТИЧЕСКОЙ ПЛАСТИЧНОСТИ В МОДЕЛЬНЫХ УСЛОВИЯХ ДИСФУНКЦИИ ГЕМАТОЭНЦЕФАЛИЧЕСКОГО БАРЬЕРА
DOI:
https://doi.org/10.5281/zenodo.22786196Ключевые слова:
гематоэнцефалический барьер, синаптическая пластичность, гиппокамп, тромбинПоддерживающие организации
Лицензия
Аннотация
Дисфункция гематоэнцефалического барьера (ГЭБ), нередко возникающая на фоне эпилептического статуса, приводит к изменению микросреды нервной ткани и вносит вклад в развитие эпилепсии. В наших предыдущих работах был предложен подход к воспроизведению ранней стадии нарушения ГЭБ, в основе которого лежит приближение ионного состава перфузионного раствора к таковому в плазме крови и добавлении тромбина в концентрации 5 Ед/мл. В этих условиях регистрировалась эпилептиформная активность как на уровне отдельных нейронов, так и на уровне нейронных сетей гиппокампа. В настоящей работе исследованы особенности синаптической передачи при моделировании дисфункции ГЭБ. Показано, что экспериментальное нарушение барьера индуцирует изменения синаптической пластичности, выражающиеся в усилении как кратковременных, так и долговременных ее форм.
Скачивания
Библиографические ссылки
1. Friedman A. Blood-brain barrier dysfunction, status epilepticus, seizures and epilepsy: a puzzle of a chicken and egg? // Epilepsia. – 2011. – Vol. 52. – P. 19–20. – DOI: 10.1111/j.1528-1167.2011.03227.x.
2. Oby E., Janigro D. The blood-brain barrier and epilepsy // Epilepsia. – 2006. – Vol. 47. – P. 1761–1774. – DOI: 10.1111/j.1528- 1167.2006.00817.x/.
3. Savotchenko A., Klymenko M., Shypshyna M., Isaev D. The role of thrombin in early-onset seizures // Frontiers in Cellular Neuroscience. – 2023. – Vol. 17. – P. 1101006. – DOI: 10.3389/fncel.2023.1101006.
4. Montagne A., Toga A.W., Zlokovic B. V. Blood-brain barrier permeability and gadolinium: benefits and potential pitfalls in research // JAMA Neurology. – 2016. – Vol. l73. – P. 13–14. – DOI: 10.1001/jamaneurol.2015.2960.
5. Singh T., Mehra A., Batabyal T., Joshi S., Kapur J. Thrombin mediates seizures following cortical injury-induced status epilepticus // Epilepsy Research. – 2025. – Vol. 2013. – P. 107549. – DOI: 10.1016/j.eplepsyres.2025.107549.
6. Tomkins O., Friedman O., Ivens S., Reiffurth C., Major S., Dreier J.P., Heinemann U., Friedman A. Blood-brain barrier disruption results in delayed functional and structural alterations in the rat neocortex // Neurobiology of Disease. – 2007. – Vol. 25. – P. 367–377. – DOI: 10.1016/j.nbd.2006.10.006.
7. Isaev D., Lushnikova I., Lunko O., Zapukhliak O., Maximyuk O., Romanov A., Skibo G., Tian C., Holmes G.L., Isaeva E. Contribution of protease-activated receptor 1 in status epilepticus induced epileptogenesis // Neurobiology of Disease. – 2015. – Vol. 78. – P. 68–76. – DOI: 10.1016/j.nbd.2015.03.026.
8. Lee K. R., Drury I., Vitarbo E. and Hoff J. T. Seizures induced by intracerebral injection of thrombin: a model of intracerebral hemorrhage // Journal of Neurosurgery. – 1997. – Vol. 87. – P. 73–78. – DOI: 10.3171/jns.1997.87.1.0073.
9. Savotchenko A. V., Chuyan E. N. Short-Term Synaptic Plasticity of Hippocampal Neural Networks under Experimentally-Induced Blood–Brain Barrier Dysfunction // Journal of Evolutionary Biochemistry and Physiology. – 2025. – Vol. 61, No. 4. – P. 1200-1208. – DOI: 10.1134/S0022093025040209.
10. Ергина Ю., Смирнова Е. In vitro модели эпилептиформной активности // Российский физиологический журнал им. И.М. Сеченова. – 2019. – № 105. – С. 954–965. – DOI: 10.1134/S0869813919080041.
11. Gingrich M. B., Traynelis S. F. Serine proteases and brain damage - is there a link? // Trends in Neuroscience. – 2000. – Vol.23, № 9. – P. 399–407. – DOI: 10.1016/s0166-2236(00)01617-9.
12. Maggio N., Cavaliere C., Papa M., Blatt I., Chapman J., Segal M. Thrombin regulation of synaptic transmission: implications for seizure onset // Neurobiology of Disease. – 2013. – Vol. 50. – P. 171–178. – DOI: 10.1016/j.nbd.2012.10.017.
13. Suzuki M., Ogawa A., Sakurai Y., Nishino A., Venohara K., Mizoi K., Yoshimoto T. Thrombin activity in cerebrospinal fluid after subarachnoid hemorrage // Stroke. – 1992. – Vol. 23. – P. 1181–1182. – DOI: 10.1161/01.str.23.8.1181.
14. Postnikova T. Y., Griflyuk A. V., Ergina J. L., Zubareva O. E., Zaitsev A. V. Administration of bacterial lipopolysaccharide during early postnatal ontogenesis induces transient impairment of long-term synaptic plasticity associated with behavioral abnormalities in young rats // Pharmaceuticals (Basel). – 2020. – Vol. 13, No. 3. – P. 48. – DOI: 10.3390/ph13030048.
15. Salar S., Lapilover E., Müller J., Hollnagel J. O., Lippmann K., Friedman A., Heinemann U. Synaptic plasticity in area CA1 of rat hippocampal slices following intraventricular application of albumin // Neurobiology of Disease. – 2016. – Vol. 91. – P. 155–165. – DOI: 10.1016/j.nbd.2016.03.008.
16. Kryukov K. A., Kim K. K., Magazanik L. G., Zaitsev A. V. Status epilepticus alters hippocampal long-term synaptic potentiation in a rat lithium-pilocarpine model // Neuroreport. – 2016. – Vol. 27, No 16. – P. 1191–1195. – DOI: 10.1097/WNR.0000000000000656.
17. Beck H., Goussakov I. V., Lie A., Helmstaedter C., Elger C. E. Synaptic plasticity in the human dentate gyrus // Journal of Neuroscience. – 2000. – Vol. 20, No 18. – P. 7080–7086. – DOI: 10.1523/JNEUROSCI.20-18-07080.2000.
18. Müller L., Tokay T., Porath K., Köhling R., Kirschstein T. Enhanced NMDA receptor-dependent LTP in the epileptic CA1 area via upregulation of NR2B // Neurobiology of Disease. – 2013. – Vol. 54. – PP. 183–193. – DOI: 10.1016/j.nbd.2012.12.011.
19. Voytenko L. P., Lushnikova I. V., Savotchenko A. V., Isaeva E. V., Skok M. V., Lykhmus O. Y., Patseva M. A., Skibo G. G. Hippocampal GABAergic interneurons coexpressing alpha7-nicotinic receptors and connexin-36 are able to improve neuronal viability under oxygen-glucose deprivation // Brain Researh. – 2015. – Vol. 1616. – P. 134–145. – DOI: 10.1016/j.brainres.2015.04.061.
20. Huemmeke M., Eysel U. T., Mittmann T. Lesion-induced enhancement of LTP in rat visual cortex is mediated by NMDA receptors containing the NR2B subunit // Journal of Physiology. – 2004. – Vol. 559. – P. 875–882. – DOI: 10.1113/jphysiol.2004.069534.
21. Aungst S. L., Kabadi S. V., Thompson S. M., Stoica B. A., Faden A. I. Repeated mild traumatic brain injury causes chronic neuroinflammation, changes in hippocampal synaptic plasticity, and associated cognitive deficits // Journal of Cerebral Blood Flow & Metabolism. – 2014. – Vol. 34, No. 7. – P. 1223–1232. – DOI: 10.1038/jcbfm.2014.75.
22. Shypshyna M., Savotchenko A., Kuznetsov K. and Veselovsky N. The effect of thrombin in the serum-adapted ionic environment on the induction of epileptiform firing activity of hippocampal cultured neurons // Fiziologichnyi Zhurnal. – 2021. – Vol. 67. – P. 3–10. – DOI: 10.15407/fz67.05.003.
23. Semenikhina M., Bogovyk R., Fedoriuk M., Nikolaienko O., Al Kury L. T., Savotchenko A., Krishtal O., Isaeva E. Inhibition of protease-activated receptor 1 ameliorates behavioral deficits and restores hippocampal synaptic plasticity in a rat model of status epilepticus // Neuroscience Letters. – 2019. – Vol. 692. – P. 64–68. – DOI: 10.1016/j.neulet.2018.10.058.
24. Itzekson Z., Maggio N., Milman A., Shavit E., Pick C. G., Chapman J. Reversal of trauma-induced amnesia in mice by a thrombin receptor antagonist // Journal of Molecular Neuroscience. – 2014. – Vol. 53, No. 1. – P. 87–95. – DOI: 10.1007/s12031-013-0200-8.
25. Klebe D., Flores J. J., McBride D.W., Krafft P. R., Rolland W. B., Lekic T., Zhang J. H. Dabigatran ameliorates post-haemorrhagic hydrocephalus development after germinal matrix haemorrhage in neonatal rat pups // Journal of Cerebral Blood Flow & Metabolism. – 2017. – Vol. 37, No. 9. – P. 3135–3149. – DOI: 10.1177/0271678X16684355.
REFERENCES
1. Friedman, A. (2011) Blood-brain barrier dysfunction, status epilepticus, seizures and epilepsy: a puzzle of a chicken and egg? Epilepsia. 52, 19–20, doi: 10.1111/j.1528-1167.2011.03227.x.
2. Oby, E., and Janigro, D. (2006) The blood-brain barrier and epilepsy. Epilepsia. 47, 1761–1774, doi: 10.1111/j.1528-1167.2006.00817.x.
3. Savotchenko, A., Klymenko, M., Shypshyna, M., Isaev, D. (2023) The role of thrombin in early-onset seizures. Front. Cell. Neurosci. 17:1101006, doi: 10.3389/fncel.2023.1101006.
4. Montagne, A., Toga, A. W., and Zlokovic, B. V. (2016). Blood-brain barrier permeability and gadolinium: benefits and potential pitfalls in research. JAMA Neurol. 73, 13–14, doi: 10.1001/jamaneurol.2015.2960.
5. Singh, T., Mehra, A., Batabyal, T., Joshi, S., Kapur, J. (2025) Thrombin mediates seizures following cortical injury-induced status epilepticus. Epilepsy Res. 2013, 107549, doi: 10.1016/j.eplepsyres.2025.107549.
6. Tomkins, O., Friedman, O., Ivens, S., Reiffurth, C.,Major, S., Dreier, J. P., et al. (2007) Blood-brain barrier disruption results in delayed functional and structural alterations in the rat neocortex. Neurobiol. Dis. 25, 367–377, doi: 10.1016/j.nbd.2006.10.006.
7. Isaev, D., Lushnikova, I., Lunko, O., Zapukhliak, O., Maximyuk, O., Romanov, A., et al. (2015) Contribution of protease-activated receptor 1 in status epilepticusinduced epileptogenesis. Neurobiol. Dis. 78, 68–76, doi: 10.1016/j.nbd.2015.03.026.
8. Lee, K. R., Drury, I., Vitarbo, E., and Hoff, J. T. (1997) Seizures induced by intracerebral injection of thrombin: a model of intracerebral hemorrhage. J. Neurosurg. 87, 73–78, doi: 10.3171/jns.1997.87.1.0073.
9. Savotchenko, A.V., Chuyan, E.N. (2025) Short-Term Synaptic Plasticity of Hippocampal Neural Networks under Experimentally-Induced Blood–Brain Barrier Dysfunction. Journal of Evolutionary Biochemistry and Physiology. 61, 1200-1208, doi: 10.1134/S0022093025040209.
10. Ergina, J. L., Smirnova, E. Y. (2019) In vitro models of epileptic-like activity. Russian Journal of Physiology. 105, 954–965, doi: 10.1134/S0869813919080041.
11. Gingrich, M. B., Traynelis, S. F. (2000) Serine proteases and brain damage – is there a link? Trends Neurosci. 23(9), 399–407, doi: 10.1016/s0166-2236(00)01617-9.
26. Maggio, N., Cavaliere, C., Papa, M., Blatt, I., Chapman, J., Segal, M. (2013) Thrombin regulation of synaptic transmission: implications for seizure onset, Neurobiol. Dis. 50, 171–178, doi: 10.1016/j.nbd.2012.10.017.
12. Suzuki, M., Ogawa, A., Sakurai, Y., Nishino, A., Venohara, K., Mizoi, K., Yoshimoto, T. (1992) Thrombin activity in cerebrospinal fluid after subarachnoid hemorrage. Stroke. 23, 1181–1182, doi: 10.1161/01.str.23.8.1181.
13. Postnikova, T. Y., Griflyuk, A. V., Ergina, J. L., Zubareva, O. E., Zaitsev, A. V. (2020) Administration of bacterial lipopolysaccharide during early postnatal ontogenesis induces transient impairment of long-term synaptic plasticity associated with behavioral abnormalities in young rats. Pharmaceuticals (Basel). 13(3), 48, doi: 10.3390/ph13030048.
14. Salar, S., Lapilover, E., Müller, J., Hollnagel, J. O., Lippmann, K., Friedman, A., Heinemann, U. (2016) Synaptic plasticity in area CA1 of rat hippocampal slices following intraventricular application of albumin. Neurobiol. Dis. 91, 155–165, doi: 10.1016/j.nbd.2016.03.008.
15. Kryukov, K. A., Kim, K. K., Magazanik, L. G., Zaitsev, A. V. (2016) Status epilepticus alters hippocampal long-term synaptic potentiation in a rat lithium-pilocarpine model. Neuroreport. 27(16), 1191–1195, doi: 10.1097/WNR.0000000000000656.
16. Beck, H., Goussakov, I. V., Lie, A., Helmstaedter, C., Elger, C. E. (2000) Synaptic plasticity in the human dentate gyrus. J. Neurosci. 20(18), 7080–7086, doi: 10.1523/JNEUROSCI.20-18-07080.2000.
17. Müller, L., Tokay, T., Porath, K., Köhling, R., Kirschstein, T. (2013) Enhanced NMDA receptor-dependent LTP in the epileptic CA1 area via upregulation of NR2B. Neurobiol. Dis. 54, 183–193, doi: 10.1016/j.nbd.2012.12.011.
18. Voytenko, L. P., Lushnikova, I. V., Savotchenko, A. V., Isaeva, E. V., Skok, M. V., Lykhmus, O. Y., Patseva, M. A., Skibo, G. G. (2015) Hippocampal GABAergic interneurons coexpressing alpha7-nicotinic receptors and connexin-36 are able to improve neuronal viability under oxygen-glucose deprivation. Brain Res. 1616, 134–145, doi: 10.1016/j.brainres..04.061.
19. Huemmeke, M., Eysel, U. T., Mittmann, T. (2004) Lesion-induced enhancement of LTP in rat visual cortex is mediated by NMDA receptors containing the NR2B subunit. J. Physiol. 559, 875–882, doi: 10.1113/jphysiol.2004.069534.
20. Aungst, S. L., Kabadi, S.V., Thompson, S. M., Stoica, B. A., Faden, A. I. (2014) Repeated mild traumatic brain injury causes chronic neuroinflammation, changes in hippocampal synaptic plasticity, and associated cognitive deficits. J. Cereb. Blood. Flow. Metab. 34(7), 1223–1232, doi: 10.1038/jcbfm.2014.75.
21. Shypshyna, M., Savotchenko, A., Kuznetsov, K., and Veselovsky, M. (2021) The effect of thrombin in the serum-adapted ionic environment on the induction of epileptiform firing activity of hippocampal cultured neurons. Fiziol. Zh. 67, 3–10, doi: 10.15407/fz67.05.003.
22. Semenikhina, M., Bogovyk, R., Fedoriuk, M., Nikolaienko, O., Al Kury, L.T., Savotchenko, A., Krishtal, O., Isaeva, E. (2019) Inhibition of protease-activated receptor 1 ameliorates behavioral deficits and restores hippocampal synaptic plasticity in a rat model of status epilepticus. Neurosci. Lett. 692, 64–68, doi: 10.1016/j.neulet.2018.10.058.
23. Itzekson, Z., Maggio, N., Milman, A., Shavit, E., Pick, C. G., Chapman, J. (2014) Reversal of trauma-induced amnesia in mice by a thrombin receptor antagonist. J. Mol. Neurosci. 53(1), 87–95, doi: 10.1007/s12031-013-0200-8.
24. Klebe, D., Flores, J. J., McBride, D. W., Krafft, P. R., Rolland, W. B., Lekic, T., Zhang, J. H. (2017) Dabigatran ameliorates post-haemorrhagic hydrocephalus development after germinal matrix haemorrhage in neonatal rat pups. J. Cereb. Blood Flow Metab. 37(9), 3135–3149, doi: 10.1177/0271678X16684355.
Загрузки
Опубликован
Выпуск
Раздел
Лицензия
Это произведение доступно по лицензии Creative Commons «Attribution-NonCommercial» («Атрибуция — Некоммерческое использование») 4.0 Всемирная.
Статьи журнала «Вестник Донецкого университета. Серия 01. Естественные науки» находятся в открытом доступе и распространяются в соответствии с условиями Лицензионного Договора с Донецким Государственным университетом, который бесплатно предоставляет авторам неограниченное распространение и самостоятельное архивирование.
