N 1–2 (179–180) 2022. P. 14–19

ON THE ROLE OF TUMOR NECROSIS FACTOR-ALPHA (TNF-α) AND NUCLEAR FACTOR p-NF-ΚB IN THE PENTYLENETETRAZOLE KINDLING PATHOGENESIS

Yozgat Bozok University, Yozgat, Turkey
University of Health Sciences, Istanbul, Turkey
Lviv National Medical University, Lviv, Ukraine
Odessa National Medical University, Odesa, Ukraine

DOI 10.54229/2226-2008-2022-1-2-2

Determining the role of endogenous factors as markers of chronic epileptic activity allows pathogenetically justifying new approaches to treating epilepsy. The aim of the work was the immunohistochemical study of the expression of the tumor necrosis factor-alpha (TNF-α) and nuclear factor p-NF-κB in the tissue of the dorsal parts of the hippocampus in rats with kindling seizures. Kindling was produced in 15 rats by three-week i.p. pentylenetetrazole (PTZ, 35.0 mg/kg) administration. 20 control group rats were injected with 0.9% NaCl solution. The avidin-biotin-peroxidase method was used in 10 control group rats for staining. The rest ten rats composed the negative control group and stained using only secondary antibodies. The color intensity of the brain sections of the control and kindling groups was compared with the color of the brain sections of the negative control group using the “Image J” program. In rats with PTZ-kindling, the level of TNF-α was 17.86+0.83 relative units (RU) and exceeded the corresponding indicator in the control group (4.78+0.14 RU), (p<0.001). The expression of p-NF-κB was 5.24+0.61 against 1.73+0.07 RU in control (p<0.001). Determination of the expression of TNF-α and NF-κB in limbic structures can be used as markers of the effectiveness of experimental treatment methods for chronic epilepsy.

Key words: seizures, cytokines, hypoxia, pentylenetetrazol, hippocamp.

REFERENCES

  1. Vezzani A. Brain Inflammation and Seizures: Evolving Concepts and New Findings in the Last 2 Decades. Epilepsy Curr. 2020 Nov-Dec;20(6_suppl):40S-43S. doi: 10.1177/1535759720948900. Epub 2020 Oct 5. PMID: 33012196; PMCID: PMC7726731 (in English).
  2. D’Ignazio L, Bandarra D, Rocha S. NF-κB and HIF crosstalk in immune responses. FEBS J. 2016;283(3):413-24 (in English).
  3. Varfolomeev E., Vucic D. Intracellular regulation of TNF activity in health and disease. Cytokine. 2018;101:26-32 (in English).
  4. Shandra AA, Godlevsky LS, Vastyanov RS, Konovalenko VL, Rapoport EN, Korobka NN The role of TNF- in amygdala kindled rats. Neurosci Res 2002; 42: 147-153 (in English).
  5. Godlevsky L.S., Muratova T.N., Kresyun N.V., Van Luijtelaar G, Coenen A. Anxiolytic and antidepressive effects of electric stimulation of the paleocerebellar cortex in pentylenetetrazol kindled rats. Acta Neurobiol Exp (Wars). 2014; 74: 456-64. PMID: 25576976 (in English).
  6. Kim, K.W.; Lee, S.J.; Kim, J.C. TNF-α upregulates HIF-1α expression in pterygium fibroblasts and enhances their susceptibility to VEGF independent of hypoxia. Exp. Eye Res.2017, 164, 74–81 (in English).
  7. Malkov MI, Lee CT, Taylor CT. Regulation of the Hypoxia-Inducible Factor (HIF) by Pro-Inflammatory Cytokines. Cells. 2021 Sep 7;10(9):2340. doi: 10.3390/cells10092340 (in English).
  8. Tao Z, Chun-Yan H, Hua P, Bin-Bin Y, Xiaoping T. Phyllathin From Phyllanthus Amarus Ameliorates Epileptic Convulsion and Kindling Associated Post-Ictal Depression in Mice via Inhibition of NF-κB/TLR-4 Pathway. Dose Response. 2020 Aug 3;18(3):1559325820946914. doi: 10.1177/1559325820946914 (in English).
  9. Akyüz E, Doğanyiğit Z, Paudel YN, Kaymak E, Yilmaz S, Uner A, et al. Increased ACh-associated immunoreactivity in autonomic centers in PTZ kindling model of epilepsy. Biomedicines. 2020; 8(5):113. doi: 10.3390/biomedicines8050113. (in English).
  10. Doğanyiğit Z, Okan A, Kaymak E, Pandır D, Silici S. Investigation of protective effects of apilarnil against lipopolysaccharide induced liver injury in rats via TLR 4/HMGB-1/NF-κB pathway. Biomed Pharmacother. 2020; 125: 109967. doi: : 10.1016/j.biopha.2020.109967. (in English).
  11. Crowe AR, Yue W. Semi-quantitative determination of protein expression using immunohistochemistry staining and analysis: an integrated protocol. Bio Protoc. 2019; 9(24): e3465. doi: 10.21769/BioProtoc.3465. (in English).
  12. Lee JW, Chun W, Lee HJ, Kim SM, Min JH, Kim DY, Kim MO, Ryu HW, Lee SU. The Role of Microglia in the Development of Neurodegenerative Diseases. Biomedicines. 2021 Oct 12;9(10):1449. doi: 10.3390/biomedicines9101449. (in English).
  13. Wang HK, Yan H, Wang K, Wang J. Dynamic regulation effect of long non-coding RNA-UCA1 on NF-kB in hippocampus of epilepsy rats. Eur Rev Med Pharmacol Sci. 2017;21(13):3113-9. (in English).
  14. Qi Y, Qian R, Jia L, Fei X, Zhang D, Zhang Y, et al. Overexpressed microRNA-494 represses RIPK1 to attenuate hippocampal neuron injury in epilepsy rats by inactivating the NF-κB signaling pathway. Cell cycle. 2020;19(11):1298-313. (in English).
  15. Wang K, Liu Y, Shi Y, Yan M, Rengarajan T, Feng X. Amomum tsaoko fruit extract exerts anticonvulsant effects through suppression of oxidative stress and neuroinflammation in a pentylenetetrazol kindling model of epilepsy in mice. Saudi J Biol Sci. 2021 Aug;28(8):4247-4254. doi: 10.1016/j.sjbs.2021.06.007. (in English).