Skip to main content

Advertisement

SpringerLink
Log in

Increased expression of proinflammatory cytokines and iNOS in the neocortical microvasculature of patients with temporal lobe epilepsy

  • Brief report
  • Published:
Immunologic Research Aims and scope Submit manuscript

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

References

  1. Vezzani A, Lang B, Aronica E. Immunity and inflammation in epilepsy. Cold Spring Harb Perspect Med. 2015;6. https://doi.org/10.1101/cshperspect.a022699.

  2. Vezzani A, Balosso S, Ravizza T. Neuroinflammatory pathways as treatment targets and biomarkers in epilepsy. Nat Rev Neurol. 2019;15:459–72. https://doi.org/10.1038/s41582-019-0217-x.

    Article  CAS  PubMed  Google Scholar 

  3. Derada Troletti C, de Goede P, Kamermans A, de Vries HE. Molecular alterations of the blood-brain barrier under inflammatory conditions: the role of endothelial to mesenchymal transition. Biochim Biophys Acta. 2016;1862:452–60. https://doi.org/10.1016/j.bbadis.2015.10.010.

    Article  CAS  PubMed  Google Scholar 

  4. van Vliet EA, Aronica E, Vezzani A, Ravizza T. Review: Neuroinflammatory pathways as treatment targets and biomarker candidates in epilepsy: emerging evidence from preclinical and clinical studies. Neuropathol Appl Neurobiol. 2018;44:91–111. https://doi.org/10.1111/nan.12444.

    Article  PubMed  Google Scholar 

  5. Leal B, Chaves J, Carvalho C, Rangel R, Santos A, Bettencourt A, et al. Brain expression of inflammatory mediators in mesial temporal lobe epilepsy patients. J Neuroimmunol. 2017;313:82–8. https://doi.org/10.1016/j.jneuroim.2017.10.014.

    Article  CAS  PubMed  Google Scholar 

  6. Kan AA, de Jager W, de Wit M, Heijnen C, van Zuiden M, Ferrier C, et al. Protein expression profiling of inflammatory mediators in human temporal lobe epilepsy reveals co-activation of multiple chemokines and cytokines. J Neuroinflammation. 2012;9. https://doi.org/10.1186/1742-2094-9-207.

  7. Dadas A, Janigro D. Breakdown of blood brain barrier as a mechanism of post-traumatic epilepsy. Neurobiol Dis. 2019;123:20–6. https://doi.org/10.1016/j.nbd.2018.06.022.

    Article  CAS  PubMed  Google Scholar 

  8. Villaseñor R, Lampe J, Schwaninger M, Collin L. Intracellular transport and regulation of transcytosis across the blood-brain barrier. Cell Mol Life Sci. 2019;76:1081–92. https://doi.org/10.1007/s00018-018-2982-x.

    Article  CAS  PubMed  Google Scholar 

  9. Marchi N, Lerner-Natoli M. Cerebrovascular remodeling and epilepsy. Neuroscientist. 2013;19:304–12. https://doi.org/10.1177/1073858412462747.

    Article  CAS  PubMed  Google Scholar 

  10. van Vliet EA, Aronica E, Gorter JA. Blood-brain barrier dysfunction, seizures and epilepsy. Semin Cell Dev Biol. 2015;38:26–34. https://doi.org/10.1016/j.semcdb.2014.10.003.

    Article  CAS  PubMed  Google Scholar 

  11. Baruah J, Vasudevan A, Köhling R. Vascular integrity and signaling determining brain development, network excitability, and epileptogenesis. Front Physiol. 2020;10. https://doi.org/10.3389/fphys.2019.01583.

  12. Ravizza T, Vezzani A. Pharmacological targeting of brain inflammation in epilepsy: therapeutic perspectives from experimental and clinical studies. Epilepsia Open. 2018;3:133–42. https://doi.org/10.1002/epi4.12242.

    Article  PubMed  PubMed Central  Google Scholar 

  13. Mercado-Gómez OF, Córdova-Dávalos L, García-Betanzo D, Rocha L, Alonso-Vanegas MA, Cienfuegos J, et al. Overexpression of inflammatory-related and nitric oxide synthase genes in olfactory bulbs from frontal lobe epilepsy patients. Epilepsy Res. 2018;148:37–43. https://doi.org/10.1016/j.eplepsyres.2018.09.012.

    Article  CAS  PubMed  Google Scholar 

  14. Veszelka S, Pásztói M, Farkas AE, Krizbai I, Ngo TK, Niwa M, et al. Pentosan polysulfate protects brain endothelial cells against bacterial lipopolysaccharide-induced damages. Neurochem Int. 2007;50:219–28. https://doi.org/10.1016/j.neuint.2006.08.006.

    Article  CAS  PubMed  Google Scholar 

  15. Lorigados Pedre L, Morales Chacón LM, Pavón Fuentes N, Robinson Agramonte MLA, Serrano Sánchez T, Cruz-Xenes RM, et al. Follow-up of peripheral IL-1β and IL-6 and relation with apoptotic death in drug-resistant temporal lobe epilepsy patients submitted to surgery. Behav Sci (Basel). 2018;8. https://doi.org/10.3390/bs8020021.

  16. Bereshchenko O, Bruscoli S, Riccardi C. Glucocorticoids, sex hormones, and immunity. Front Immunol. 2018;9. https://doi.org/10.3389/fimmu.2018.01332.

  17. Savic I. Sex differences in human epilepsy. Exp Neurol. 2014;259:38–43. https://doi.org/10.1016/j.expneurol.2014.04.009.

    Article  PubMed  Google Scholar 

  18. Asadi-Pooya AA, Myers L, Valente K, Restrepo AD, D’Alessio L, Sawchuk T, et al. Sex differences in demographic and clinical characteristics of psychogenic nonepileptic seizures: a retrospective multicenter international study. Epilepsy Behav. 2019. https://doi.org/10.1016/j.yebeh.2019.05.045.

  19. Savic I, Engel J Jr. Structural and functional correlates of epileptogenesis - does gender matter? Neurobiol Dis. 2014;70:69–73. https://doi.org/10.1016/j.nbd.2014.05.028.

    Article  PubMed  PubMed Central  Google Scholar 

  20. Abbot NJ, Friedman A. Overview and introduction: the blood–brain barrier in health and disease. Epilepsia. 2012;53:1–6. https://doi.org/10.1111/j.1528-1167.2012.03696.x.

    Article  Google Scholar 

  21. Löscher W, Friedman A. Structural, molecular, and functional alterations of the blood-brain barrier during epileptogenesis and epilepsy: a cause, consequence, or both? Int J Mol Sci. 2020;21. https://doi.org/10.3390/ijms21020591.

  22. Gales JM, Prayson RA. Chronic inflammation in refractory hippocampal sclerosis-related temporal lobe epilepsy. Ann Diagn Pathol. 2017; https://doi.org/10.1016/j.anndiagpath.2017.05.009.

  23. Oby E, Janigro D. The blood-brain barrier and epilepsy. Epilepsia. 2006;47:1761–74. https://doi.org/10.1111/j.1528-1167.2006.00817.x.

    Article  CAS  PubMed  Google Scholar 

  24. Schindler CK, Pearson EG, Bonner HP, So NK, Simon RP, Prehn JH, et al. Caspase-3 cleavage and nuclear localization of caspase-activated DNase in human temporal lobe epilepsy. J Cereb Blood Flow Metab. 2006;26:583–9. https://doi.org/10.1038/sj.jcbfm.9600219.

    Article  CAS  PubMed  Google Scholar 

  25. Narkilahti S, Jutila L, Alafuzoff I, Karkola K, Paljärvi L, Immonen A, et al. Increased expression of caspase 2 in experimental and human temporal lobe epilepsy. NeuroMolecular Med. 2007;9:129–44. https://doi.org/10.1007/bf02685887.

    Article  CAS  PubMed  Google Scholar 

  26. Strauss KI, Elisevich KV. Brain region and epilepsy-associated differences in inflammatory mediator levels in medically refractory mesial temporal lobe epilepsy. J Neuroinflammation. 2016;13:270. https://doi.org/10.1186/s12974-016-0727-z.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Terrone G, Balosso S, Pauletti A, Ravizza T, Vezzani A. Inflammation and reactive oxygen species as disease modifiers in epilepsy. Neuropharmacology. 2019;167:107742. https://doi.org/10.1016/j.neuropharm.2019.107742.

    Article  CAS  PubMed  Google Scholar 

  28. O'Dell CM, Das A, Wallace G IV, Ray SK, Banik NL. Understanding the basic mechanisms underlying seizures in mesial temporal lobe epilepsy and possible therapeutic targets: a review. J Neurosci Res. 2012;90:913–24. https://doi.org/10.1002/jnr.22829.

    Article  CAS  PubMed  Google Scholar 

  29. Liimatainen S, Lehtimäki K, Palmio J, Alapirtti T, Peltola J. Immunological perspectives of temporal lobe seizures. J Neuroimmunol. 2013;263:1–7. https://doi.org/10.1016/j.jneuroim.2013.08.001.

    Article  CAS  PubMed  Google Scholar 

  30. Voirin AC, Perek N, Roche F. Inflammatory stress induced by a combination of cytokines (IL-6, IL-17, TNF-α) leads to a loss of integrity on bEnd.3 endothelial cells in vitro BBB model. Brain Res. 2020. https://doi.org/10.1016/j.brainres.2020.146647.

  31. Klement W, Garbelli R, Zub E, Rossini L, Tassi L, Girard B, et al. Seizure progression and inflammatory mediators promote pericytosis and pericyte-microglia clustering at the cerebrovasculature. Neurobiol Dis. 2018;113:70–81. https://doi.org/10.1016/j.nbd.2018.02.002.

    Article  CAS  PubMed  Google Scholar 

  32. Li Y, Chen J, Zeng T, Lei D, Chen L, Zhou D. Expression of HIF-1α and MDR1/P-glycoprotein in refractory mesial temporal lobe epilepsy patients and pharmacoresistant temporal lobe epilepsy rat model kindled by coriaria lactone. Neurol Sci. 2014;35:1203–8. https://doi.org/10.1007/s10072-014-1681-0.

    Article  PubMed  Google Scholar 

  33. Gong GH, An FM, Wang Y, Bian M, Wang D, Wei CX. MiR-153 regulates expression of hypoxia-inducible factor-1α in refractory epilepsy. Oncotarget. 2018;9:8542–7. https://doi.org/10.18632/oncotarget.24012.

    Article  PubMed  PubMed Central  Google Scholar 

  34. Li TR, Jia YJ, Wang Q, Shao XQ, Zhang P, Lv RJ. Correlation between tumor necrosis factor alpha mRNA and microRNA-155 expression in rat models and patients with temporal lobe epilepsy. Brain Res. 2018;1700:56–65. https://doi.org/10.1016/j.brainres.2018.07.013.

    Article  CAS  PubMed  Google Scholar 

  35. Nikolic L, Shen W, Nobili P, Virenque A, Ulmann L, Audinat E. Blocking TNFα-driven astrocyte purinergic signaling restores normal synaptic activity during epileptogenesis. Glia. 2018;66:2673–83. https://doi.org/10.1002/glia.23519.

    Article  PubMed  Google Scholar 

Download references

Acknowledgments

The authors thank their institutions that provided the economic and technical support to carry out this work.

CRediT authorship contribution statement

Conceptualization and writing—original draft preparation: José Luis Castañeda-Cabral, Mónica E. Ureña-Guerrero, and Luisa Rocha; Methodology: José Luis Castañeda-Cabral, Adacrid Colunga-Durán, and Maria de los Angeles Nuñez-Lumbreras; Formal analysis, Data curation, and Investigation: José Luis Castañeda-Cabral; Validation: Maria A. Deli; Funding acquisition and Resources: Mónica E. Ureña-Guerrero, Carlos Beas-Zárate, Sandra Orozco-Suárez, Mario Alonso-Vanegas, Rosalinda Guevara-Guzmán, and Luisa Rocha; Supervision: Mónica E. Ureña-Guerrero and Luisa Rocha.

Funding

The authors thank the Consejo Nacional de Ciencia y Tecnología (CONACYT) of Mexico for the partial and additional support given through the postdoctoral fellowship nos. 710924 and 740404 to J.L. Castañeda-Cabral and grants to C. Beas-Zárate (no. 177594), L. Rocha (no. A3-S-26782), and R. Guevara-Guzmán (no. 261481) approved to research groups.

Author information

Author notes

  1. Mario Alonso-Vanegas

    Present address: Centro Internacional de Cirugía de Epilepsia, Hospital HMG-Coyoacán, Ciudad de Mexico, Mexico

Authors and Affiliations

  1. Departamento de Farmacobiología, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional (Cinvestav), Sede Sur, Calz. de los Tenorios 235, Granjas Coapa, 14330, Ciudad de México, Mexico

    José Luis Castañeda-Cabral, Adacrid Colunga-Durán, Maria de los Angeles Nuñez-Lumbreras & Luisa Rocha

  2. Departamento de Biología Celular y Molecular, Centro Universitario de Ciencias Biológicas y Agropecuarias (CUCBA), Universidad de Guadalajara, Zapopan, Jalisco, Mexico

    José Luis Castañeda-Cabral, Mónica E. Ureña-Guerrero & Carlos Beas-Zárate

  3. Unidad de Investigación Médica en Enfermedades Neurológicas, Hospital de Especialidades, Centro Médico Nacional Siglo XXI, IMSS, Ciudad de México, Mexico

    Sandra Orozco-Suárez

  4. Servicio de Neurocirugía, Instituto Nacional de Neurología y Neurocirugía “Manuel Velasco Suárez” (INNNMVS), Ciudad de México, Mexico

    Mario Alonso-Vanegas

  5. Departamento de Fisiología, Facultad de Medicina, Universidad Nacional Autónoma de México, Ciudad de México, Mexico

    Rosalinda Guevara-Guzmán

  6. Institute of Biophysics, Biological Research Centre, Hungarian Academy of Sciences, Szeged, Hungary

    Maria A. Deli

Authors
  1. José Luis Castañeda-Cabral
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Mónica E. Ureña-Guerrero
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Carlos Beas-Zárate
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Adacrid Colunga-Durán
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Maria de los Angeles Nuñez-Lumbreras
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Sandra Orozco-Suárez
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Mario Alonso-Vanegas
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Rosalinda Guevara-Guzmán
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Maria A. Deli
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Luisa Rocha
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to José Luis Castañeda-Cabral.

Ethics declarations

All procedures were performed following the ethical principles of the Declaration of Helsinki for human research, and an informed consent form was signed by each patient. In addition, the full research protocol was approved by the Ethics Committee in Research of the INNNMVS (agreement No. CEI/058/16).

Conflict of interest

The authors declare that they have no conflict of interest.

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Castañeda-Cabral, J.L., Ureña-Guerrero, M.E., Beas-Zárate, C. et al. Increased expression of proinflammatory cytokines and iNOS in the neocortical microvasculature of patients with temporal lobe epilepsy. Immunol Res 68, 169–176 (2020). https://doi.org/10.1007/s12026-020-09139-3

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12026-020-09139-3

Search

Navigation