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Changes in vimentin immunoreactivity in the structures of the hippocampus in patients with drug-resistant epilepsy

https://doi.org/10.56618/20712693_2022_14_3_89

Abstract

Epilepsy is a major public health problem worldwide. In more than 30 % of patients, the disease progresses to drug-resistant epilepsy (DRE) and requires surgical treatment. A large number of works are devoted to the development of pathogenetic treatment taking into account the molecular genetic status, in particular, the expression of various neuroprotective proteins, including the distribution of vimentin in brain tissues, which belongs to the proteins of intermediate filaments of tissues of mesodermal origin, is of great interest.

PURPOSE OFTHIS STUDY. To study the immunoreactivity of vimentin in the structures of the hippocampus in patients with DRE.

MATERIALS AND METHODS. The biopsy material of hippocampal fragments of 15 patients (6 women, 9 men) with DRE, mean age 32.6 years, was studied. Autopsy material from 7 patients with an average age of 51 years was used as a comparison group. Histological sections stained with hematoxylin and eosin were studied, as well as the results of immunohistochemical reactions with antibodies to vimentin. The result of the reaction was evaluated by calculating the densitometric density of stained cells in 5 fields of view of the dentate gyrus zones, fields CA1 and CA4. Statistical analysis was carried out using the program Statistica v.10.

RESULTS. When studying the histological material of the hippocampus, atrophic changes in its structures were revealed up to the development of sclerosis of various types. When conducting immunohistochemical reactions with vimentin, bright immunopositivity was revealed in the cytoplasm of ischemic neurons, neurons of the granular layer of the dentate gyrus, astrocytes, and microglia. The study of the densitometric density of vimentin-stained cells revealed: in the CA1 nucleus 0,12–0,56 (μ = 0,028±0,008); in the CA4 nucleus 0,014–0,044 (μ = 0,029±0,008); in the dentate gyrus 0,01–0,045 (μ = 0,027±0,009). Statistical data processing resulted in a significant difference according to the Mann-Whitney, Kolmogorov-Smirnov criteria (p <0,05) in all the studied areas.

CONCLUSION. Thus, in the structures of the hippocampus in patients with DRE, there is a significant increase in the immunoreactivity of vimentin in the neurons of the nuclei and dispersed neurons of the dentate gyrus, associated with the activation of neurogenesis. On the other hand, vimentin-associated remodeling of astrocytes with the formation of a glial scar prevents the repair of nervous tissue in the area of the epileptic focus and is a pathogenetic link in the formation of hippocampal sclerosis.

About the Authors

D. A. Sitovskaya
Polenov Russian Scientific Research Institute of Neurosurgery — branch of Almazov National Medical Research Centre$ Federal State budgetary Educational Institution of Higher Education «St. Petersburg State Pediatric Medical University»
Russian Federation

Darya A. Sitovskaya

191014, Mayakovskogo st., 12, Saint-Petersburg$194100, Litovskaya st., 2, Saint-Petersburg



A. A. Eremina
Federal State budgetary Educational Institution of Higher Education «St. Petersburg State Pediatric Medical University»
Russian Federation

Anastasiya O. Eremina

194100, Litovskaya st., 2, Saint-Petersburg



T. V. Sokolova
Polenov Russian Scientific Research Institute of Neurosurgery — branch of Almazov National Medical Research Centre
Russian Federation

Tatyana V. Sokolova

191014, Mayakovskogo st., 12, Saint-Petersburg



Yu. M. Zabrodskaya
Polenov Russian Scientific Research Institute of Neurosurgery — branch of Almazov National Medical Research Centre
Russian Federation

Yuliya M. Zabrodskaya

191014, Mayakovskogo st., 12, Saint-Petersburg



References

1. Sheng J., Liu S., Qin H., et al. Drug-Resistant epilepsy and surgery. Curr Neuropharmacol. 2018; 16(1): 17–28. https://doi.org/10.2174/1570159X15666170504123316. PMID: 28474565

2. Sone D. Making the Invisible Visible: Advanced Neuroimaging Techniques in Focal Epilepsy. Front Neurosci. 2021 Jul 27; 15:699176. https://doi.org/10.3389/fnins.2021.699176. PMID: 34385902

3. Crespel A, Rigau V, Coubes P, Rousset MC, de Bock F, Okano H, Baldy-Moulinier M, Bockaert J, Lerner-Natoli M. Increased number of neural progenitors in human temporal lobe epilepsy. Neurobiol Dis. 2005 Aug;19(3):436–50. doi: 10.1016/j.nbd.2005.01.020. PMID: 16023586

4. Qin Z, Kreplak L, Buehler MJ. Hierarchical structure controls nanomechanical properties of vimentin intermediate filaments. PLoS One. 2009 Oct 6;4(10): e7294. doi: 10.1371/journal.pone.0007294. PMID: 19806221; PMCID: PMC2752800

5. Yamada T, Kawamata T, Walker DG, McGeer PL. Vimentin immunoreactivity in normal and pathological human brain tissue. Acta Neuropathol. 1992;84(2):157–62. doi: 10.1007/BF00311389. PMID: 1523971

6. Levin EC, Acharya NK, Sedeyn JC, Venkataraman V, D’Andrea MR, Wang HY, Nagele RG. Neuronal expression of vimentin in the Alzheimer’s disease brain may be part of a generalized dendritic damageresponse mechanism. Brain Res. 2009 Nov 17;1298:194–207. doi: 10.1016/j.brainres.2009.08.072. Epub 2009 Sep 1. PMID: 19728994

7. Dahl D. The vimentin-GFA protein transition in rat neuroglia cytoskeleton occurs at the time of myelination. J Neurosci Res. 1981;6(6):741–8. doi: 10.1002/jnr.490060608. PMID: 7334533

8. Stichel CC, Müller CM, Zilles K. Distribution of glial fibrillary acidic protein and vimentin immunoreactivity during rat visual cortex development. J Neurocytol. 1991 Feb;20(2):97–108. doi: 10.1007/BF01279614. PMID: 2027041

9. Missler M, Eins S, Böttcher H, Wolff JR. Postnatal development of glial fibrillary acidic protein, vimentin and S 100 protein in monkey visual cortex: evidence for a transient reduction of GFAP immunoreactivity. Brain Res Dev Brain Res. 1994 Oct 14;82(1– 2):103–17. doi: 10.1016/0165–3806(94)901538. PMID: 7842498

10. Hutchins JB, Casagrande VA. Vimentin: changes in distribution during brain development. Glia. 1989;2(1):55–66. doi: 10.1002/glia.440020107. PMID: 2523339

11. Cope EC, Gould E. Adult Neurogenesis, Glia, and the Extracellular Matrix. Cell Stem Cell. 2019 May 2;24(5):690–705. doi: 10.1016/j.stem.2019.03.023. PMID: 31051133

12. Wilhelmsson U, Pozo-Rodrigalvarez A, Kalm M, de Pablo Y, Widestrand Å, Pekna M, Pekny M. The role of GFAP and vimentin in learning and memory. Biol Chem. 2019 Aug 27;400(9):1147–1156. doi: 10.1515/hsz2019–0199. PMID: 31063456

13. Morrow CS, Porter TJ, Xu N, Arndt ZP, Ako-Asare K, Heo HJ, Thompson EAN, Moore DL. Vimentin Coordinates Protein Turnover at the Aggresome during Neural Stem Cell Quiescence Exit. Cell Stem Cell. 2020 Apr 2;26(4):558–568.e9. doi: 10.1016/j.stem.2020.01.018. Epub 2020 Feb 27. PMID: 32109376; PMCID: PMC7127969

14. Bayir E, Sendemir A. Role of Intermediate Filaments in Blood-Brain Barrier in Health and Disease. Cells. 2021 Jun 5;10(6):1400. doi: 10.3390/cells10061400. PMID: 34198868; PMCID: PMC8226756

15. Yu YT, Chien SC, Chen IY, Lai CT, Tsay YG, Chang SC, Chang MF. Surface vimentin is critical for the cell entry of SARS-CoV. J Biomed Sci. 2016 Jan 22;23:14. doi: 10.1186/s1292901602347. PMID: 26801988; PMCID: PMC4724099

16. Zou Y, He L, Huang SH. Identification of a surface protein on human brain microvascular endothelial cells as vimentin interacting with Escherichia coli invasion protein IbeA. Biochem Biophys Res Commun. 2006 Dec 22;351(3):625–30. doi: 10.1016/j.bbrc.2006.10.091. Epub 2006 Oct 26. PMID: 17083913

17. Villarreal R, Manzer HS, Keestra-Gounder AM, Doran KS. Vimentin Regulates Chemokine Expression and NOD 2 Activation in Brain Endothelium during Group B Streptococcal Infection. Infect Immun. 2021 Nov 16;89(12): e0034021. doi: 10.1128/IAI.00340–21. Epub 2021 Sep 7. PMID: 34491787; PMCID: PMC8594594

18. Potokar M, Stenovec M, Gabrijel M, Li L, Kreft M, Grilc S, Pekny M, Zorec R. Intermediate filaments attenuate stimulationdependent mobility of endosomes/lysosomes in astrocytes. Glia. 2010 Aug;58(10):1208–19. doi: 10.1002/glia.21000. PMID: 20544856

19. Wilhelmsson U, Li L, Pekna M, Berthold CH, Blom S, Eliasson C, Renner O, Bushong E, Ellisman M, Morgan TE, Pekny M. Absence of glial fibrillary acidic protein and vimentin prevents hypertrophy of astrocytic processes and improves post-traumatic regeneration. J Neurosci. 2004 May 26;24(21):5016–21. doi: 10.1523/JNEUROSCI.0820–04.2004. PMID: 15163694; PMCID: PMC6729371

20. O’Leary LA, Davoli MA, Belliveau C, Tanti A, Ma JC, Farmer WT, Turecki G, Murai KK, Mechawar N. Characterization of VimentinImmunoreactive Astrocytes in the Human Brain. Front Neuroanat. 2020 Jul 30;14:31. doi: 10.3389/fnana.2020.00031. PMID: 32848635; PMCID: PMC7406576

21. Jing R, Wilhelmsson U, Goodwill W, Li L, Pan Y, Pekny M, Skalli O. Synemin is expressed in reactive astrocytes in neurotrauma and interacts differentially with vimentin and GFAP intermediate filament networks. J Cell Sci. 2007 Apr 1;120(Pt 7):1267–77. doi: 10.1242/jcs.03423. Epub 2007 Mar 13. PMID: 17356066

22. Jing R, Pizzolato G, Robson RM, Gabbiani G, Skalli O. Intermediate filament protein synemin is present in human reactive and malignant astrocytes and associates with ruffled membranes in astrocytoma cells. Glia. 2005 Apr 15;50(2):107–20. doi: 10.1002/glia.20158. PMID: 15657940

23. Boison D, Steinhäuser C. Epilepsy and astrocyte energy metabolism. Glia. 2018 Jun;66(6):1235–1243. doi: 10.1002/glia.23247. Epub 2017 Oct 17. PMID: 29044647; PMCID: PMC5903956

24. Pekny M, Pekna M, Messing A, Steinhäuser C, Lee JM, Parpura V, Hol EM, Sofroniew MV, Verkhratsky A. Astrocytes: a central element in neurological diseases. Acta Neuropathol. 2016 Mar;131(3):323– 45. doi: 10.1007/s0040101515131. Epub 2015 Dec 15. PMID: 26671410

25. Patodia S, Paradiso B, Ellis M, Somani A, Sisodiya SM, Devinsky O, Thom M. Characterisation of medullary astrocytic populations in respiratory nuclei and alterations in sudden unexpected death in epilepsy. Epilepsy Res. 2019 Nov;157:106213. doi: 10.1016/j.eplepsyres.2019.106213. Epub 2019 Oct 1. PMID: 31610338; PMCID: PMC7002840

26. Jiang SX, Slinn J, Aylsworth A, Hou ST. Vimentin participates in microglia activation and neurotoxicity in cerebral ischemia. J Neurochem. 2012 Aug;122(4):764–74. doi: 10.1111/j.1471–4159.2012.07823.x. Epub 2012 Jun

27. Erratum in: J Neurochem. 2021 Jul;158(2):571–572. PMID: 22681613 27. Pekny M, Wilhelmsson U, Tatlisumak T, Pekna M. Astrocyte activation and reactive gliosis-A new target in stroke? Neurosci Lett. 2019 Jan 10;689:45–55. doi: 10.1016/j.neulet.2018.07.021. Epub 2018 Jul 17. PMID: 30025833

28. Wilhelmsson U, Li L, Pekna M, Berthold CH, Blom S, Eliasson C, Renner O, Bushong E, Ellisman M, Morgan TE, Pekny M. Absence of glial fibrillary acidic protein and vimentin prevents hypertrophy of astrocytic processes and improves post-traumatic regeneration. J Neurosci. 2004 May 26;24(21):5016–21. doi: 10.1523/JNEUROSCI.0820–04.2004. PMID: 15163694; PMCID: PMC6729371


Review

For citations:


Sitovskaya D.A., Eremina A.A., Sokolova T.V., Zabrodskaya Yu.M. Changes in vimentin immunoreactivity in the structures of the hippocampus in patients with drug-resistant epilepsy. Russian Neurosurgical Journal named after Professor A. L. Polenov. 2022;14(3):89-96. (In Russ.) https://doi.org/10.56618/20712693_2022_14_3_89

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