Prophylactic effect of intranasal oxytocin on brain damage and neurological disorders in global cerebral ischemia in mice | ||
| Iranian Journal of Basic Medical Sciences | ||
| مقاله 12، دوره 24، شماره 1، فروردین 2021، صفحه 79-84 اصل مقاله (1.18 M) | ||
| نوع مقاله: Original Article | ||
| شناسه دیجیتال (DOI): 10.22038/ijbms.2020.50265.11456 | ||
| نویسندگان | ||
| Marzieh Saffari1؛ Shahein Momenabadi2؛ Abbas Ali Vafaei2؛ Abedin Vakili1، 2؛ Mahdi Zahedi Khorasani* 1، 2 | ||
| 1Research Center of Physiology, Semnan University of Medical Sciences, Semnan, Iran | ||
| 2Department of Physiology, Faculty of Medicine, Semnan University of Medical Sciences, Semnan, Iran | ||
| چکیده | ||
| Objective(s): A few experimental studies have shown the therapeutic effects of oxytocin on focal cerebral ischemia. In this study, the prophylactic effect of intranasal oxytocin on brain damage was investigated in a cerebral ischemic model. Materials and Methods: Intranasal oxytocin (8 IU/per mouse) was prescribed daily for one week. Cerebral ischemia was performed through bilateral common carotid artery occlusion (BCCAO) for 20 min and then blood flow was restored for 24 hr. Finally, neurological disorders, spatial learning and memory, neuronal death, and neuronal apoptosis were assessed in CA1, CA3, and dentate gyrus. Also, levels of interleukin-1β (IL-1β) and Tumor necrosis factor-alpha (TNFα) were measured in the hippocampus. Results: Induction of global ischemia leads to neurological disorders and impairment of spatial learning and memory that are improved by pre-treatment with oxytocin (p <0.01). Cresyl violet staining showed that pretreatment with oxytocin significantly reduced the number of dead nerve cells in CA1, CA3, and dentate gyrus by 40.7, 32, and 34.3%, respectively. Also, positive TUNEL cells in CA1, CA3, and dental gyrus decreased by 15, 30, and 27%, respectively. In addition, levels of TNFα and IL-1β, which were extensively increased in ischemic mice, were significantly reduced with oxytocin pre-treatment. Conclusion: Pre-treatment of oxytocin reduces ischemic damage and improves neurological function and spatial memory. The neuroprotective effect of oxytocin is mediated by a decrease in cell death, apoptosis, and inflammatory mediators TNFα and IL-1β. Pre-treatment with oxytocin may be useful in people who are prone to stroke. | ||
| کلیدواژهها | ||
| Apoptosis Interleukin؛ 1β Oxytocin Stroke Tumor necrosis factor | ||
| مراجع | ||
|
1. Hook V, Lietz CB, Podvin S, Cajka T, Fiehn O. Diversity of neuropeptide cell-cell signaling molecules generated by proteolytic processing revealed by neuropeptidomics mass spectrometry. J Am Soc Mass Spectrom 2018; 29: 807-816. 2. Keshavarzi Z, Khaksari Hadad M, Zahedi MJ, Bahrami A. The effects of female sex steroids on gastric secretory responses of rat following traumatic brain injury. Iran J Basic Med Sci 2011; 14: 231-239. 3. Ebrahimi SM, Aboutaleb N, Nobakht M. Consequences of ischemic preconditioning of kidney: comparing between male and female rats. Iran J Basic Med Sci 2012;15:1148-1153. 4. Alimohamadi R, Fatemi I, Naderi S, Hakimizadeh E, Rahmani MR, Allahtavakoli M. Protective effects of Vitex agnus-castus in ovariectomy mice following permanent middle cerebral artery occlusion. Iran J Basic Med Sci 2019 Sep; 22: 1097–1101. 5. Appelros P, Stegmayr B, Terént A. Sex differences in stroke epidemiology: a systematic review. Stroke 2009; 40:1082-1090. 6. Zingg HH, Laporte SA. The oxytocin receptor. Trends Endocrinol & Metabolism 2003; 14: 222-227. 7. Evans SL, Dal Monte O, Noble P, Averbeck BB. Intranasal oxytocin effects on social cognition: a critique. Brain Res 2014;1580: 69-77. 8. Erbas O, Korkmaz HA, Oltulu F, Aktug H, Yavasoglu A, Akman L, et al. Oxytocin alleviates cisplatin-induced renal damage in rats. Iran J Basic Med Sci 2014;17:747-752. 9. Kaneko Y, Pappas C, Tajiri N, Borlongan CV. Oxytocin modulates GABA A R subunits to confer neuroprotection in stroke in vitro. Scientific Rep 2016: 6; 1-10 10. Moghadam SE, Tameh AA, Vahidinia Z, Atlasi MA, Bafrani HH, Naderian H. Neuroprotective effects of oxytocin hormone after an experimental stroke model and the possible role of calpain-1. J Stroke Cerebrovasc Dis 2018;27:724-732. 11. Asadi Y, Gorjipour F, Behrouzifar S, Vakili A. Irisin peptide protects brain against ischemic injury through reducing apoptosis and enhancing BDNF in a rodent model of stroke. Neurochemical Res 2018;43:1549-1560. 12. Garcia JH, Wagner S, Liu KF, Hu Xj. Neurological deficit and extent of neuronal necrosis attributable to middle cerebral artery occlusion in rats: statistical validation. Stroke 1995;26:627-635. 13. Rahmati H, Momenabadi S, Vafaei AA, Bandegi AR, Mazaheri Z, Vakili A. Probiotic supplementation attenuates hippocampus injury and spatial learning and memory impairments in a cerebral hypoperfusion mouse model. Mol Biol Rep 2019;46:4985-4995. 14. Akdemir A, Erbas O, Gode F, Ergenoglu M, Yeniel O, Oltulu F, et al. Protective effect of oxytocin on ovarian ischemia-reperfusion injury in rats. Peptides 2014;55:126-130. 15. Gonzalez-Reyes A, Menaouar A, Yip D, Danalache B, Plante E, Noiseux N, et al. Molecular mechanisms underlying oxytocin-induced cardiomyocyte protection from simulated ischemia–reperfusion. Mol Cell Endocrinol 2015; 412:170-181. 16. Momenabadi S, Vafaei AA, Bandegi AR, Zahedi-Khorasani M, Mazaheri Z, Vakili A. Oxytocin reduces brain injury and maintains blood–brain barrier integrity after ischemic stroke in mice. NeuroMolecular Med 2020:1-15. 17. Karelina K, Stuller KA, Jarrett B, Zhang N, Wells J, Norman GJ, et al. Oxytocin mediates social neuroprotection after cerebral ischemia. Stroke 2011;42:3606-3611. 18. Japundžić-Žigon N, Lozić M, Šarenac O, Murphy D. Vasopressin & Oxytocin in Control of the Cardiovascular System: An Updated Review. Curr Neuropharmacol 2020; 18:14-33. 19. Dayi A, Cetin F, Sisman AR, Aksu I, Tas A, Gönenc S, et al. The effects of oxytocin on cognitive defect caused by chronic restraint stress applied to adolescent rats and on hippocampal VEGF and BDNF levels. Med Sci monitor: Int Med J Exp Clin Res 2015;21:69. 20. Wilkins HM, Swerdlow RH. TNFα in cerebral ischemia: another stroke against you? J Neurochem 2015;132:369-372. 21. Olmos G, Lladó J. Tumor necrosis factor alpha: a link between neuroinflammation and excitotoxicity. Mediators Inflamm 2014;2014: 1-12. 22. Zaremba J, Losy J. Early TNF‐α levels correlate with ischaemic stroke severity. Acta Neurologica Scandinavica 2001;104:288-295. 23. Rock KL, Latz E, Ontiveros F, Kono H. The sterile inflammatory response. Annu Rev Immunol 2009; 28:321-342. 24. Rothwell N. Interleukin-1 and neuronal injury: mechanisms, modification, and therapeutic potential. Brain, Behav Immun 2003; 17: 152-157. 25. Hutchinson PJ, O’Connell MT, Rothwell NJ, Hopkins SJ, Nortje J, Carpenter KL, et al. Inflammation in human brain injury: Intracerebral concentrations of IL-1 α, IL-1 β, and their endogenous inhibitor IL-1ra. J Neurotrauma 2007; 24: 1545-1547. 26. Arend WP. The balance between IL-1 and IL-1Ra in disease. Cytokine Growth Factor Rev 2002; 13:323-40. 27. Emsley H, Smith C, Georgiou R, Vail A, Hopkins S, Rothwell N, et al. A randomised phase II study of interleukin-1 receptor antagonist in acute stroke patients. J Neurol, Neurosurg & Psychiatry. 2005;76:1366-1372. 28. Oeckinghaus A, Ghosh S. The NF-κB family of transcription factors and its regulation. Cold Spring Harbor perspect Biol 2009; 1: a000034. 29. Lee JI, Burckart GJ. Nuclear factor kappa B: important transcription factor and therapeutic target. J Clin Pharmacol 1998;38:981-993. 30. Zhao H, Chen Z, Xie L-J, Liu G-F. Suppression of TLR4/NF-κB signaling pathway improves cerebral ischemia–reperfusion injury in rats. Mol Neurobiol 2018;55:4311-4319. 31. Berti R, Williams AJ, Moffett JR, Hale SL, Velarde LC, Elliott PJ, et al. Quantitative Real-Time RT—PCR Analysis of Inflammatory Gene Expression Associated with Ischemia-Reperfusion Brain Injury. J Cereb Blood Flow & Metabolism 2002;22:1068-1079. 32. Khori V, Alizadeh AM, Khalighfard S, Heidarian Y, Khodayari H. Oxytocin effects on the inhibition of the NF-κB/miR195 pathway in mice breast cancer. Peptides 2018;107:54-60. | ||
|
آمار تعداد مشاهده مقاله: 878 تعداد دریافت فایل اصل مقاله: 448 |
||