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The Effect of Inflammation on Pentylenetetrazol Induced Seizures in Rats

Document Type : Original Article

Authors

1 Neurology Research Center, Kerman University of Medical Sciences, Kerman, Iran

2 Endocrinology and Metabolism Research Center, Kerman University of Medical Sciences, Kerman, Iran

3 Sirjan School of Medical Sciences, Sirjan, Iran

Abstract

Introduction: Epilepsy is a common and debilitating neurological disorder associated with reduced quality of life and increased mortality. This study investigated the hypothesis of Traditional Persian Medicine about the effect of local inflammation on seizures using a rat model.
Methods: Adult male Wistar rats (n = 28) were divided into four groups: One control group (CTL) and three experimental groups in which epilepsy was induced 6 (INF-EPI-6), 14 (INF-EPI-14), or 28 days (INF-EPI-28) after carrageenan-induced paw inflammation. Seizures were triggered using intraperitoneal injection of pentylenetetrazol (PTZ). Seizure latency, duration, severity, mortality, and serum levels of IL-6 and CRP were assessed.
Results: Serum IL-6 levels significantly increased in the experimental groups compared to control (CTL: 7.16 ± 1.88 pg/ml; INF-EPI-6: 24.10 ± 1.61, P < 0.01; INF-EPI-14: 13.32 ± 1.03, P < 0.05; INF-EPI-28: 14.01 ± 1.15, P < 0.05). CRP levels remained unchanged across groups. Seizure severity significantly decreased in INF-EPI-14 (1.14 ± 0.45) vs. control (3 ± 0.37, P < 0.05), though latency and duration showed no significant differences. IL-6 levels were negatively correlated with seizure severity in INF-EPI-6 (P < 0.05), and CRP levels showed a similar correlation in INF-EPI-14 (P < 0.01).
Conclusion: Pre-existing peripheral inflammation may reduce seizure severity, partially supporting Jorjani’s theory. However, further studies are needed to elucidate the underlying mechanisms.

Highlights

 Maryam Rameshk  (Google Scholar) (PubMed)

 Hossein Ali Ebrahimi Meimand  (Google Scholar) (PubMed)

Keywords

Main Subjects

References
  1. Ebrahimi H, Shafa M, Hakimzadeh Asl S. Prevalence of active epilepsy in Kerman, Iran: a house-based survey. Acta Neurol Taiwan 2012;21(3):115-24.
  2. Ebrahimi Meimand HA, Jahani Moghaddam MK. Evaluation of fasting effects during the holy month of Ramadan on patients with epileptic attacks who visited the emergency room. J Kerman Univ Med Sci 2023;30(5):267-70. doi:10.34172/ jkmu.2023.45
  3. Bai N, Yin M, Zhang H, Li Z. The experiences of adolescents and young adults with epilepsy: a systematic review and meta-synthesis of qualitative studies. Epilepsy Behav 2023;140:109086. doi:10.1016/j.yebeh.2023.109086
  4. Damla E, Aktaş An investigation of stigma and self-management in individuals diagnosed with epilepsy. Epilepsy Behav 2023;149:109494. doi:10.1016/j.yebeh.2023.109494
  5. Ebrahimi H. Current drug treatments of epilepsy. Curr J Neurol 2009;8(25):377-390.
  6. Stickley A, Neligan A, Baburin A, Jasilionis D, Krumins J, Martikainen P, et al. Educational inequalities in epilepsy mortality in the Baltic countries and Finland in 2000-2015. Sci Rep 2022;12(1):4597. doi:10.1038/s41598-022-08456-x
  7. Thijs RD, Surges R, O’Brien TJ, Sander JW. Epilepsy in adults. Lancet 2019;393(10172):689-701. doi:10.1016/s0140- 6736(18)32596-0
  8. Ebrahimi H. Challenges in the treatment of epilepsy. J Kerman Univ Med Sci 2012;19(2):212-24.
  9. Tashakori-Miyanroudi M, Ramazi S, Hashemi P, Nazari- Serenjeh M, Baluchnejadmojarad T, Roghani M. Acetyl-L-carnitine exerts neuroprotective and anticonvulsant effect in kainate murine model of temporal lobe epilepsy. J Mol Neurosci 2022;72(6):1224-33. doi:10.1007/s12031-022-01999-8
  10. Camfield P, Camfield C. Epileptic syndromes in childhood: clinical features, outcomes, and treatment. Epilepsia 2002;43 Suppl 3:27-32. doi:10.1046/j.1528-1157.43.s.3.3.x
  11. Mula M, Trimble MR. Antiepileptic drug-induced cognitive adverse effects: potential mechanisms and contributing factors. CNS Drugs 2009;23(2):121-37. doi:10.2165/00023210- 200923020-00003
  12. Laxer KD, Trinka E, Hirsch LJ, Cendes F, Langfitt J, Delanty N, et al. The consequences of refractory epilepsy and its treatment. Epilepsy Behav 2014;37:59-70. doi:10.1016/j. yebeh.2014.05.031
  13. Begley C, Wagner RG, Abraham A, Beghi E, Newton C, Kwon CS, et al. The global cost of epilepsy: a systematic review and extrapolation. Epilepsia 2022;63(4):892-903. doi:10.1111/ epi.17165
  14. Strzelczyk A, Reese JP, Dodel R, Hamer HM. Cost of epilepsy: a systematic review. Pharmacoeconomics 2008;26(6):463-76. doi:10.2165/00019053-200826060-00002
  15. Raeiszadeh M, Rameshk M, Kalantari-Khandani S. Medicinal herbs effective for gray hair in traditional Persian medicine. Curr Tradit Med 2021;7(3):336-42. doi:10.2174/221508380 6999200909120529
  16. The Persian Translation of Al-Qanun Fi Al-Tibb (The Canon of Medicine). Tehran, Iran: Soroush Publication; 1983.
  17. Jorjani SI. Zakhire Kharazmshahi. Qom: Institute for Natural Medicine Recovery; 2012.
  18. Jorjani SE. Al-Aghraz Al-Tibb va Al-Mabahes Al-Alaieah. Tehran: Tehran University; 2006.
  19. Emami SA. The history of Persian medicine at a glance, emphasizing the life and works of Avicenna. In: Schulz H, Emami SA, Nadjafi F, eds. Medicinal Plants used in Traditional Persian Medicine. London, UK: CABI; 2023. p. 1-26. doi:10.1079/9781800621671.0001
  20. Pourahmad J. History of medical sciences in Iran. Iran J Pharm Res 2008;7(2):93-9. doi:10.22037/ijpr.2010.750
  21. Abu-Asab M, Amri H, Micozzi MS. Avicenna’s Medicine: A New Translation of the 11th-Century Canon with Practical Applications for Integrative Health Care. New York: Simon and Schuster; 2013.
  22. Chishti GM, Chishti HG. The Traditional Healer’s Handbook: A Classic Guide to the Medicine of Avicenna. USA: Inner Traditions/Bear & Co; 1991.
  23. Rameshk M. The cause of kidney stone formation and treatment from the perspective of conventional and traditional Persian medicine. Tradit Integr Med 2024;9(1):74-91. doi: 10.18502/tim.v9i1.15091
  24. Rameshk M, Kalantari-Khandani S. Types of wound and wound healing from the perspective of traditional Iranian medicine (TIM). In: Keel JE, ed. A Closer Look at Wound Infections and Healing. New York: Nova Science Publishers; 2019. p. 1-66.
  25. Tafazoli V, Tavakoli A, Mosaffa-Jahromi M, Cooley K, Pasalar Approach of Persian medicine to health and disease. Adv Integr Med 2022;9(1):3-8. doi:10.1016/j.aimed.2021.07.007
  26. Zhang ZC, Zhang SJ, Jin B, Wu Y, Yang XF, Yu B, et al. Ciclamilast ameliorates adjuvant-induced arthritis in a rat model. Biomed Res Int 2015;2015:786104. doi:10.1155/2015/786104
  27. Lolignier S, Amsalem M, Maingret F, Padilla F, Gabriac M, Chapuy E, et al. Nav1.9 channel contributes to mechanical and heat pain hypersensitivity induced by subacute and chronic inflammation. PLoS One 2011;6(8): e23083. doi:10.1371/ journal.pone.0023083
  28. Grigoletto J, de Oliveira CV, Grauncke AC, de Souza TL, Souto NS, de Freitas ML, et al. Rosmarinic acid is anticonvulsant against seizures induced by pentylenetetrazol and pilocarpine in mice. Epilepsy Behav 2016;62:27-34. doi:10.1016/j. yebeh.2016.06.037
  29. Guardia T, Rotelli AE, Juarez AO, Pelzer LE. Anti-inflammatory properties of plant flavonoids. Effects of rutin, quercetin and hesperidin on adjuvant arthritis in rat. Farmaco 2001;56(9):683-7. doi:10.1016/s0014-827x(01)01111-9
  30. Janisset N, Romariz SA, Hashiguchi D, Quintella ML, Gimenes C, Yokoyama T, et al. Partial protective effects of cannabidiol against PTZ-induced acute seizures in female rats during the proestrus-estrus transition. Epilepsy Behav 2022;129:108615. doi:10.1016/j.yebeh.2022.108615
  31. Ghoz EH, Freed WJ. Effects of betaine on seizures in the rat. Pharmacol Biochem Behav 1985;22(4):635-40. doi:10.1016/0091-3057(85)90287-4
  32. Lüttjohann A, Fabene PF, van Luijtelaar G. A revised Racine’s scale for PTZ-induced seizures in rats. Physiol Behav 2009;98(5):579-86. doi:10.1016/j.physbeh.2009.09.005
  33. Du G, Chen X, Todorovic MS, Shu S, Kapur J, Bayliss DA. TASK channel deletion reduces sensitivity to local anesthetic-induced seizures. Anesthesiology 2011;115(5):1003-11. doi:10.1097/ALN.0b013e3182343660
  34. Pereira AV, Góis MB, Lera KR, Falkowski-Temporini GJ, Massini PF, Drozino RN, et al. Histopathological lesions in encephalon and heart of mice infected with Toxoplasma gondii increase after Lycopodium clavatum 200dH treatment. Pathol Res Pract 2017;213(1):50-7. doi:10.1016/j.prp.2016.11.003
  35. Chiang N, Serhan CN. Structural elucidation and physiologic functions of specialized pro-resolving mediators and their receptors. Mol Aspects Med 2017;58:114-29. doi:10.1016/j. mam.2017.03.005
  36. Kaplan H, Thompson RC, Trumble BC, Wann LS, Allam AH, Beheim B, et al. Coronary atherosclerosis in indigenous South American Tsimane: a cross-sectional cohort study. Lancet 2017;389(10080):1730-9. doi:10.1016/s0140- 6736(17)30752-3
  37. Gruol DL. IL-6 regulation of synaptic function in the CNS. Neuropharmacology 2015;96(Pt A):42-54. doi:10.1016/j. neuropharm.2014.10.023
  38. Scorza CA, Marques MJ, da Silva SG, da Graça Naffah- Mazzacoratti M, Scorza FA, Cavalheiro EA. Status epilepticus does not induce acute brain inflammatory response in the Amazon rodent Proechimys, an animal model resistant to epileptogenesis. Neurosci Lett 2018;668:169-73. doi:10.1016/j.neulet.2017.02.049
  39. de Beer FC, Baltz ML, Munn EA, Feinstein A, Taylor J, Bruton C, et al. Isolation and characterization of C-reactive protein and serum amyloid P component in the rat. Immunology 1982;45(1):55-70.
  40. Kang S, Kishimoto T. Interplay between interleukin-6 signaling and the vascular endothelium in cytokine storms. Exp Mol Med 2021;53(7):1116-23. doi:10.1038/s12276-021-00649-0
  41. Hartman J, Frishman WH. Inflammation and atherosclerosis: a review of the role of interleukin-6 in the development of atherosclerosis and the potential for targeted drug therapy. Cardiol Rev 2014;22(3):147-51. doi:10.1097/ crd.0000000000000021
  42. Li Y, Zhao J, Yin Y, Li K, Zhang C, Zheng Y. The role of IL-6 in fibrotic diseases: molecular and cellular mechanisms. Int J Biol Sci 2022;18(14):5405-14. doi:10.7150/ijbs.75876
  43. Gabay C. Interleukin-6 and chronic inflammation. Arthritis Res Ther 2006;8(Suppl 2): S3. doi:10.1186/ar1917
  44. Alapirtti T, Waris M, Fallah M, Soilu-Hänninen M, Mäkinen R, Kharazmi E, et al. C-reactive protein and seizures in focal epilepsy: a video-electroencephalographic study. Epilepsia 2012;53(5):790-6. doi:10.1111/j.1528-1167.2012.03449.x
  45. Azam Khan M. Exir Azam. Tehran: Institute of Medical History, Research Institute for Islamic and Complementary Medicine; 2008. [Persian].
  46. Ghafari S, Esmaeili S, Naghibi F, Mosaddegh M. Plants used to treat “tabe rebá” (malaria like fever) in Iranian traditional medicine. Int J Tradit Herb Med 2013;1(6):168-76.
  47. Chen L, He Z, Qin L, Li Q, Shi X, Zhao S, et al. Antitumor effect of malaria parasite infection in a murine Lewis lung cancer model through induction of innate and adaptive immunity. PLoS One 2011;6(9): e24407. doi:10.1371/journal. pone.0024407
  48. Liu Q, Yang Y, Tan X, Tao Z, Adah D, Yu S, et al. Plasmodium parasite as an effective hepatocellular carcinoma antigen glypican-3 delivery vector. Oncotarget 2017;8(15):24785-96. doi:10.18632/oncotarget.15806

 

Journal of Kerman University of Medical Sciences
Volume 33
Pages 1-8
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