Effect of Agomelatine on Ischemic Damage in Experimental Head Trauma Model in Rats

Abstract

Objective: This study aims to investigate the effect of agomelatine on ischemic injury in an experimentally created head trauma model in rats. Materials and Methods: Groups: 1) control (C) incisions were made to the coronal and lambdoid sutures and a steel disc was placed without creating a controlled impact acceleration model; 2) head trauma (HT) did not receive any treatment after head trauma with a controlled impact acceleration model; 3) agomelatine (A) 20 mg/kg oral agomelatine given for 7 d after incisions were made to the coronal and lambdoid sutures and a steel disc was placed without creating a controlled impact acceleration model; 4) head trauma+agomelatine (HT-A) 20 mg/kg oral agomelatine given for 7 d after head trauma with a controlled impact acceleration model. The rats were humanely euthanized after the study by ethical protocols, and blood and tissue samples were taken. Biochemical (tumor necrosis factor [TNF]-α and interleukin [IL]-6) and histopathological analyses (terminal deoxynucleotidyl transferase dUTP nick end labeling [TUNEL]) were conducted from these samples. Results: A significant difference was found in TNF-α between the HT and HT-A groups (p<0.05). There was a statistically significant increase in IL-6 in the HT group compared to that in the HT-A group (p<0.01). In the histopathological analyses, a decrease in TUNEL-positive cells was observed in the HT-A group compared to that in the H group Conclusion: As a result, a decrease in both apoptotic cells and inflammatory responses was observed in the HT-A group.

Keywords

• Head Trauma
• TNF-α
• IL-6
• Agomelatine
• Rat

References

1. Adams JH, Graham DI, Scott G, Parker LS, Doyle D. Brain damage in fatal non-missile head injury. J Clin Pathol. 1980; 33:1132-1145.
2. Albert-Weissenberger C, Sirén AL. Experimental traumatic brain injury. Experimental & translational stroke medicine, 2010; 2; 1-8.
3. Bayir H, Clark RSB, Kochanek PM. Promising strategies to minimize secondary brain injury after head trauma. Crit Care Med. 2003; 31:112-117.
4. Beck GC, Brinkkoetter P, Hanusch C, et al. Clinical review: Immunomodulatory effects of dopamine in general inflammation. Critical Care. 2004; 8(6):485-491.
5. Bramlett H, Dietrich D. Quantitative structural changes in white and gray matter 1 year following traumatic brain injury in rats. Acta Neuropathol. 2002; 103:607-614.
6. Byrnes KR, Loane DJ, Stoica BA, Zhang J, Faden AI. Delayed mGluR5 activation limits neuroinflammation and neurodegeneration after traumatic brain injury. J Neuroinflammation. 2012; 9:43.
7. Carrillo‐Vico A, García‐Mauriño S, Calvo JR, Guerrero JM. Melatonin counteracts the inhibitory effect of PGE 2 on IL‐2 production in human lymphocytes via its mt1 membrane receptor. The FASEB Journal. 2003; 17:755-757.
8. Chesnut RM, Marshall LF, Klauber MR, et al. The role of secondary brain injury in determining outcome from severe head injury. J Trauma. 1993; 34:216-222.

9. Chumboatong W, Thummayot S, Govitrapong P, Tocharus C, Jittiwat J, Tocharus J. Neuroprotection of agomelatine against cerebral ischemia/reperfusion injury through an antiapoptotic pathway in rat. Neurochem. Int. 2017; 102;114-122.
10. Colin A, Reggers J, Castronovo V, Ansseau M. Lipids, depression and suicide. Encephale. 2003; 29:49-58.
11. Dantzer R, O’Connor JC, Lawson MA, Kelley KW. Inflammation-associated depression: From serotonin to kynurenine. Psychoneuroendocrinology. 2011; 36:426-436.
12. Davalos D, Grutzendler J, Yang G, et al. ATP mediates rapid microglial response to local brain injury in vivo. Nat Neurosci. 2005; 8:752-758.
13. Favero G, Franceschetti L, Bonomini F, Rodella LF, Rezzani R. Melatonin as an anti-ınflammatory agent modulating ınflammasome activation. Int J Endocrinol. 2017; 2017:1-13.
14. Fei W, Jiao W, Feng X, Chen X, Wang Y. Intermittent hypoxia mimicking obstructive sleep apnea aggravates early brain injury following ich via neuroinflammation and apoptosis. Mol. Med. Rep. 2021; 24(5);1-11.
15. Feuerstein GZ, Wang X, Barone FC. The role of cytokines in the neuropathology of stroke and neurotrauma. Neuroimmunomodulation. 1998; 5:143-159.
16. Gałecki P, Mossakowska-Wójcik J, Talarowska M. The anti-inflammatory mechanism of antidepressants – SSRIs, SNRIs. Prog Neuropsychopharmacol Biol Psychiatry. 2018; 80:291-294.
17. Ghirnikar RS, Lee YL, Eng LF. Inflammation in traumatic brain injury: Role of cytokines and chemokines. Neurochem Res. 1998; 23(3):329-340.
18. Habtemariam S, Daglia M, Sureda A, Selamoglu Z, Fuat Gulhan M, Mohammad Nabavi S. Melatonin and respiratory diseases: A Review. Curr Top Med Chem. 2016; 17:467-488.
19. Hardman JM, Manoukian A. Pathology of head trauma. Neuroimaging Clin N Am. 2002; 12:175-187.
20. Haroon E, Raison CL, Miller AH. Psychoneuroimmunology meets neuropsychopharmacology: Translational implications of the impact of inflammation on behavior. Neuropsychopharmacology. 2012; 37:137-162.
21. Hong N, Ye Z, Lin Y, Liu W, Xu N, Wang Y. Agomelatine prevents angiotensin ii-induced endothelial and mononuclear cell adhesion. Aging. 2021; 13(14);18515-18526.
22. Hu Y, Feng X, Chen J, Wu Y, Shen L. Hydrogen‑rich saline alleviates early brain injury through inhibition of necroptosis and neuroinflammation via the ros/ho‑1 signaling pathway after traumatic brain injury. Exp Ther Med. 2021; 23(2);1-10.
23. Irwin MR, Miller AH. Depressive disorders and immunity: 20 years of progress and discovery. Brain Behav Immun. 2007; 21:374-383.
24. Jeong H-K, Ji K, Min K, Joe E-H. Brain Inflammation and Microglia: Facts and Misconceptions. Exp Neurobiol. 2013; 22:59-67.
25. Kang J, Koo O, Kwon D, et al. Effects of melatonin on in vitro maturation of porcine oocyte and expression of melatonin receptor RNA in cumulus and granulosa cells. J Pineal Res. 2009; 46:22-28.
26. Karamustafalıoğlu O, Baran E. Agomelatine and mode of action. J. Mood Disord. 2012; 2:6-13.
27. Kinnunen K, Greenwood R, Powell J, et al. White matter damage and cognitive impairment after traumatic brain injury. Brain. 2010; 134(2);449-463.
28. Kumar RG, Boles JA, Wagner AK. Chronic inflammation after severe traumatic brain ınjury. J Head Trauma Rehabil. 2015; 30(6):369-381.
29. Leonard BE. Impact of inflammation on neurotransmitter changes in major depression: An insight into the action of antidepressants. Prog Neuropsychopharmacol Biol Psychiatry. 2014; 48:261-267.
30. Liu H-D, Li W, Chen Z-R, et al. Expression of the NLRP3 ınflammasome in cerebral cortex after traumatic brain injury in a rat model. Neurochem Res. 2013; 38:2072-2083.
31. MacKay RJ. Brain injury after head trauma: pathophysiology, diagnosis, and treatment. Vet Clin North Am Equine Pract. 2004 20(1):199-216.
32. Maes M, Leonard BE, Myint AM, Kubera M, Verkerk R. The new ‘5-HT’ hypothesis of depression: Cell-mediated immune activation induces indoleamine 2,3-dioxygenase, which leads to lower plasma tryptophan and an increased synthesis of detrimental tryptophan catabolites (TRYCATs), both of which contribute to the onset of depression. Prog Neuropsychopharmacol Biol Psychiatry. 2011; 35:702-721.
33. Maes M. Evidence for an immune response in major depression: A review and hypothesis. Prog Neuropsychopharmacol Biol Psychiatry. 1995; 19:11–38.
34. Mahmood MAN, Alhadidi Q, Abdulrahman Hussain S, Hussain SA, Mohammed Ali Mahmood N, Mahmood Jum K. Dose-Dependent anti-inflammatory activity of melatonin in experimental animal model of chronic inflammation. Global J. Pharmacol. 2010; 4:66-70.
35. Mauriz JL, Collado PS, Veneroso C, Reiter RJ, González‐Gallego J. A review of the molecular aspects of melatonin’s anti‐inflammatory actions: recent insights and new perspectives. J Pineal Res. 2013; 54:1-14.
36. Mirzaei F, Siahsangi P, Naseri Alavi SA. Letter: Comment on “Can serum glucose level in early admission predict outcome in patients with severe head trauma?” World Neurosurg. 2016; 92:572.
37. Molteni R, Macchi F, Zecchillo C, et al. Modulation of the inflammatory response in rats chronically treated with the antidepressant agomelatine. Eur Neuropsychopharmacol. 2013; 23(11):1645-1655.
38. Morganti-Kossmann C, Semple B, Ziebell J, Yan E, Bye N, Kossmann T. Modulation of Immune Response by Head Injury. New Insights to Neuroimmune Biology. Canada: Elsevier; 2010. pp.193-220.
39. Nesterowicz M, Lauko K, Żendzian‐Piotrowska M, Ładny J, Zalewska A, Maciejczyk M. Agomelatine's antiglycoxidative action—in vitro and in silico research and systematic literature review. Front. Psychiatry. 2023; 14; 1164459.
40. Park HJ, Kim HJ, Ra J, et al. Melatonin inhibits lipopolysaccharide‐induced CC chemokine subfamily gene expression in human peripheral blood mononuclear cells in a microarray analysis. J Pineal Res. 2007; 43:121-129.
41. Popoli M. Agomelatine. CNS Drugs. 2009; 23:27-34.
42. Raison CL, Capuron L, Miller AH. Cytokines sing the blues: inflammation and the pathogenesis of depression. Trends Immunol. 2006; 27:24-31.
43. Roozenbeek B, Maas AIR, Menon DK. Changing patterns in the epidemiology of traumatic brain injury. Nat Rev Neurol. 2013; 9:231-236.
44. Sabouri E, Majdi A, Jangjui P, Rahigh Aghsan S, Naseri Alavi SA. Neutrophil-to-lymphocyte ratio and traumatic brain ınjury: A Review Study. World Neurosurg. 2020; 140:142-147.
45. Salehpour F, Bazzazi A, Aghazadeh J, et al. What do you expect from patients with severe head trauma? Asian J Neurosurg. 2018; 13:660-663.
46. Savran M, Aslankoc R, Ozmen O, et al. Agomelatine could prevent brain and cerebellum injury against LPS-induced neuroinflammation in rats. Cytokine. 2020; 127:154957.
47. Schmidt OI, Heyde CE, Ertel W, Stahel PF. Closed head injury-an inflammatory disease? Brain Res Rev. 2005; 48:388-399.
48. Shlosberg D, Benifla M, Kaufer D, Friedman A. Blood-brain barrier breakdown as a therapeutic target in traumatic brain injury. Nat Rev Neurol. 2010; 6:393-403.
49. Straub RH, Günzler C, Miller LE, Cutolo M, Schölmerıch J, Schıll S. Anti‐inflammatory cooperativity of corticosteroids and norepinephrine in rheumatoid arthritis synovial tissue in vivo and in vitro. The FASEB Journal. 2002; 16:993-1000.
50. Sundman M, Doraiswamy P, Morey R. Neuroimaging assessment of early and late neurobiological sequelae of traumatic brain injury: implications for cte. Front. Neurosci. 2015 9;334
51. Tompkins P, Tesiram Y, Lerner M, et al. Brain Injury: Neuro-Inflammation, cognitive deficit, and magnetic resonance imaging in a model of blast ınduced traumatic brain ınjury. J Neurotrauma. 2013; 30:1888-1897.
52. Uzbay İT. Agomelatin: Genel bilgiler, farmakolojisi ve kullanım güvenliği. Turkish J Clin Psy. 2011; 15:9-19.
53. Wagner AK, Brett CA, McCullough EH, et al. Persistent hypogonadism influences estradiol synthesis, cognition and outcome in males after severe TBI. Brain Inj. 2012; 26:1226-1242.
54. Wu H, Wei M, Li N, et al. Clopidogrel-Induced Gastric Injury in Rats is Attenuated by Stable Gastric Pentadecapeptide BPC 157. Drug Des Devel Ther. 2020; 14:5599-5610.
55. Yahyavi‐Firouz‐Abadi N, Tahsili‐Fahadan P, Ghahremani MH, Dehpour AR. Melatonin enhances the rewarding properties of morphine: involvement of the nitric oxidergic pathway. J Pineal Res. 2007; 42:323-329.
56. Yang X, Zu H, Zhao Y, Yao K. Agomelatine prevents amyloid plaque deposition, tau phosphorylation, and neuroinflammation in app/ps1 mice. Front. aging neurosci. 20022; 13;766410.
57. Yao K, Zhao Y, Zu H (2019). Melatonin receptor stimulation by agomelatine prevents Aβ-induced tau phosphorylation and oxidative damage in PC12 cells. Drug Des Devel Ther. 2019; 13;387-396.
58. Yu G-M, Kubota H, Okita M, Maeda T. The anti-inflammatory and antioxidant effects of melatonin on LPS-stimulated bovine mammary epithelial cells. PLoS One. 2017; 12:e0178525.