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miR-17/20’nin Sıçanların Subaraknoid Kanama Modelinde Gelişen Vazospazm Üzerine Etkisi

Yıl 2022, Cilt: 6 Sayı: 3, 256 - 262, 31.12.2022
https://doi.org/10.30565/medalanya.1152279

Öz

Amaç: Mevcut çalışmamızın amacı, ratlarda oluşturulan subaraknoid kanama (SAH) modelinde melatonin ve miRNA-17/20 uygulamasının basiller arterde gelişen vazospazm ve damar hasarı üzerine etkisinin araştırılmasıdır.

Yöntemler: Çalışmada kullanılan 36 adet sıçan 6 gruba ayrılmıştır; Sham, SAH, SAH+NegmiRNA, SAH+MEL, SAH-miRs-17/20 group, SAH+MEL+miRs-17/20. Sıçanlara anestezi altında SAH modeli uygulandı. Kafanın ön bölgesinden dikey bir kesi ile cilt açılarak kemiğe ulaşıldı. İnsizyondan sonra, kuyruk arterinden toplanan 120 µL heparinize olmayan taze otolog arteriyel kan aseptik koşullar altında 10 saniyede yavaşça prekiazmatik sisternaya enjekte edildi. Sham grubunda kan enjeksiyonu dışında tüm basamaklar SAH grubuyla aynıydı. SAH+NegmiRs-17/20 grubunda, miRs-17/20 miRNA Mimic Negative Control#1 SAH operasyonundan 1 saat sonra uygulandı. SAH+MEL grubunda, SAH operasyonundan 1 saat sonra 10 mg/kg melatonin intraperitoneal olarak verildi. SAH-miRs-17/20 grubundaysa SAH operasyonundan 1 saat sonra intranazal olarak mimic-miR-17 ve mimic-miR-20 verildi. SAH+MEL+miRs-17/20 grubunda, SAH operasyonundan 1 saat sonra intranazal mimic-miR-17 ile intraperitoneal melatonin (10 mg/kg) uygulandı. Deney sonunda sıçanlardan basiller arteri de içeren beyin örnekleri alınıp rutin doku takip işlemlerine tabi tutuldu. Sonrasında H-E yöntemi ile boyanan histolojik kesitlerde damar örnekleri vazospazm, tunica mediada ödem ve lamina elastica internada kıvrımlanma kriterleri açısından değerlendirilip derecelendirildi.

Bulgular: SAH modeli oluşturulan sıçanlarda, SAH modeli sonrası melatonin ve miRs-17/20’nin birlikte uygulanmasının damar duvarında oluşan vazospazm ve ödem oluşmasını anlamlı şekilde azalttığı gösterilmiştir. SAH sonrası miRs-17/20 uygulamasının da tek başına damar duvarında ödem gelişmesini ve vazospazma bağlı lamina elastica internada kıvrımlanmayı azalttığı ortaya konmuştur.

Sonuç: Çalışmamızda, miRs-17/20’nin damar duvarında vazospazmı azaltabileceği, ödemi de azaltarak damar hasarını önleyebileceği gösterilmiştir.

Kaynakça

  • 1. Suarez JI, Bershad EM. Aneurysmal subarachnoid hemorrhage. Stroke (Pathophysiology, Diagnosis, and Management). Editor: James C. Grotta, Gregory W. Albers, 6th edition. Science Direct. 2016:516–36. doi: 10.1016/B978-0-323-29544-4.00029-3.
  • 2. Connolly ES, Rabinstein AA, Carhuapoma JR, Derdeyn CP, Dion J, Higashida RD, et al. Guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke. 2012;43(6):1711–37. doi: 10.1161/STR.0b013e3182587839.
  • 3. Lovelock CE, Rinkel GJ, Rothwell PM. Time trends in outcome of subarachnoid hemorrhage: Population-based study and systematic review. Neurology. 2010;74(19):1494-1501 doi: 10.1212/WNL.0b013e3181dd42b3.
  • 4. Pluta RM, Hansen-Schwartz J, Dreier J, Vajkoczy P, Macdonald RL, Nishizawa Z, et al. Cerebral vasospasm following subarachnoid hemorrhage: time for a new world of thought. Neurol Res. 2009;31(2):151–8. doi: 10.1179/174313209X393564.
  • 5. Barker FG, Heros RC. Clinical aspects of vasospasm. Neurosurg Clin N Am. 1990;1(2):277-288. PMID: 2136141
  • 6. Wang Y, Liu Y, Li Y, Liu B, Wu P, Xu S, et al. Protective effects of astaxanthin on subarachnoid hemorrhage-induced early brain injury: Reduction of cerebral vasospasm and improvement of neuron survival and mitochondrial function. Acta Histochem. 2019;121(1):56-63. doi: 10.1016/j.acthis.2018.10.014.
  • 7. Baggott CD, Aagaard-Kienitz B. Cerebral Vasospasm. Neurosurg Clin N Am. 2014;25(3):497-528. doi: 10.1016/j.nec.2014.04.008.
  • 8. Pluta RM, Afshar JKB, Boock RJ, Oldfield EH. Temporal changes in perivascular concentrations of oxyhemoglobin, deoxyhemoglobin, and methemoglobin after subarachnoid hemorrhage. J Neurosurg. 1998;88(3):557-561. doi: 10.3171/jns.1998.88.3.0557.
  • 9. Bartel DB. MicroRNAs: Genomics, biogenesis, mechanism, and function. Cell. 2004;116(2): 281-297. doi: 10.1016/S0092-8674(04)00045-5.
  • 10. Yu Z, Wang C, Wang M, Li Z, Casimiro MC, Liu M, et al. A cyclin D1/microRNA 17/20 regulatory feedback loop in control of breast cancer cell proliferation. J Cell Biol. 2008;182(3):509-17. doi: 10.1083/jcb.200801079. 11. Sonkoly E, Pivarcsi A. microRNAs in inflammation. Int Rev Immunol. 2009;28(6):535-61. doi: 10.3109/08830180903208303.
  • 12. Gupta P, Bhattacharjee S, Sharma AR, Sharma G, Lee SS, Chakraborty C. miRNAs in Alzheimer Disease. A Therapeutic Perspective. Curr Alzheimer Res. 2017;14(11):1198-1206. doi: 10.2174/1567205014666170829101016.
  • 13. Mogilyansky E, Rigoutsos I. The miR-17/92 cluster: a comprehensive update on its genomics, genetics, functions and increasingly important and numerous roles in health and disease. Cell Death Differ. 2013;20:1603-14. doi: 10.1038/cdd.2013.125.
  • 14. Liu NK, Wang XF, Lu QB, Xu XM: Altered microRNA expression following traumatic spinal cord injury. Exp Neurol. 2009;219(2):424-29. doi: 10.1016/j.expneurol.2009.06.015.
  • 15. Pandi-Perumal SR, Trakht I, Srinivasan V, Spence DW, Maestroni GJ, Zisapel N, et al. Physiological effects of melatonin: role of melatonin receptors and signal transduction pathways. Prog Neurobiol. 2008;85(3):335-53. doi: 10.1016/j.pneurobio.2008.04.001.
  • 16. Cardinali, D. P. Melatonin: clinical perspectives in neurodegeneration. Front Endocrinol (Lausanne). 2019;10:480. doi: 10.3389/fendo.2019.00480.
  • 17. Ding K, Xu J, Wang H, Zhang L, Wu Y, Li T. Melatonin protects the brain from apoptosis by enhancement of autophagy after traumatic brain injury in mice. Neurochem Int. 2015:91:46-54. doi: 10.1016/j.neuint.2015.10.008.
  • 18. Tsai MC, Chen WJ, Tsai MS, Ching CH, Chuang JI. Melatonin attenuates brain contusion-induced oxidative insult, inactivation of signal transducers and activators of transcription 1, and upregulation of suppressor of cytokine signaling-3 in rats. J Pineal Res. 2011;51(2):233-245. doi: 10.1111/j.1600-079X.2011.00885.x.
  • 19. National Research Council (US) Committee for the Update of the Guide for the Care and Use of Laboratory Animals. Guide for the Care and Use of Laboratory Animals. 8th ed. Washington (DC): National Academies Press (US); 2011. doi:10.17226/12910.
  • 20. Prunell GF, Mathiesen T, Svendgaard NA. A new experimental model in rats for study of the pathophysiology of subarachnoid hemorrhage. Neuroreport. 2002;13(18):2553-6. doi: 10.1097/00001756-200212200-00034.
  • 21. Pekince A, Kuzeyli K, Çakır E, Usul H, Karaarslan G, Baykal S, et al. Biochemical and hystopathological effects of H1 receptor blocker, papaverine and nimodipin in experimental cerebral vasospasm. J Turkish Cereb Vasc Dis, 2003:9(1):13-18.
  • 22. Malçok ÜA, Şehitoğlu MH, Büyük B, Sancak EB, Taş Hİ. Protective effect of metformin against lithium-induced cerebral neurotoxicity in rats. Med Science. 2021;10(2):350-5 doi: 10.5455/medscience.2020.12.253.
  • 23. Muehlschlegel S. Subarachnoid Hemorrhage. Continuum (Minneap Minn). 2018;24(6):1623-57. doi: 10.1212/CON.0000000000000679.
  • 24. Al-Khindi T, Macdonald RL, Schweizer TA. Cognitive and functional outcome after aneurysmal subarachnoid hemorrhage. Stroke. 2010;41(8):e519–e536. doi: 10.1161/STROKEAHA.110.581975.
  • 25. Li S, Yang S, Sun B, Hang C. Melatonin attenuates early brain injury after subarachnoid hemorrhage by the JAK-STAT signaling pathway. Int J Clin Exp Pathol. 2019;12(3):909-915. PMID: 31933900

Effect of miRs-17/20 on vasospasm in subarachnoid hemorrhage model of rats

Yıl 2022, Cilt: 6 Sayı: 3, 256 - 262, 31.12.2022
https://doi.org/10.30565/medalanya.1152279

Öz

Aim: To investigate the effects of melatonin and miRNA-17/20 administration on vasospasm and vascular damage on the bacillary artery in the Subarachnoid hemorrhage (SAH) model of rats.

Methods: Rats were divided into 6 groups: Sham, SAH, SAH+NegmiRNA, SAH+MEL, SAH-miRs-17/20 group, SAH+MEL+miRs-17/20. For creating the SAH model the skin was cut with a vertical incision in the anterior region of the head.120 µL of fresh non-heparinized autologous arterial blood collected from the tail artery was injected into the prechiasmatic cistern under aseptic conditions. All steps in the Sham were the same as in the SAH group, except for blood injection. In the SAH+NegmiRs-17/20, miRs-17/20 miRNA Mimic-Negative Control#1 was administered 1 hour after SAH operation. In the SAH+MEL,10 mg/kg melatonin was administered intraperitoneally 1 hour after the SAH operation. In the SAH-miRs-17/20, mimic-miR-17 and mimic-miR-20 were given intranasally 1 hour after the SAH operation. In the SAH+MEL+miRs-17/20,intranasal mimic-miR-17 and intraperitoneal melatonin were administered 1 hour after the SAH operation. Brain samples, including the bacillary artery, were taken and subjected to routine tissue processing procedures. Vessel samples were evaluated and graded in histological sections stained with the H-E method in terms of vasospasm, edema in the tunica media, and folding of the lamina elastica interna.

Results: The co-administration of melatonin and miRs-17/20 reduced the vasospasm and edema formation in the vessel wall. It has also been demonstrated that the application of miRs-17/20 after SAH alone reduces the development of edema in the vessel wall and folding of the internasal lamina elastica due to vasospasm.

Conclusion: It has been shown that miRs-17/20 can reduce vasospasm in the vessel wall and prevent vessel damage by reducing edema.

Kaynakça

  • 1. Suarez JI, Bershad EM. Aneurysmal subarachnoid hemorrhage. Stroke (Pathophysiology, Diagnosis, and Management). Editor: James C. Grotta, Gregory W. Albers, 6th edition. Science Direct. 2016:516–36. doi: 10.1016/B978-0-323-29544-4.00029-3.
  • 2. Connolly ES, Rabinstein AA, Carhuapoma JR, Derdeyn CP, Dion J, Higashida RD, et al. Guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke. 2012;43(6):1711–37. doi: 10.1161/STR.0b013e3182587839.
  • 3. Lovelock CE, Rinkel GJ, Rothwell PM. Time trends in outcome of subarachnoid hemorrhage: Population-based study and systematic review. Neurology. 2010;74(19):1494-1501 doi: 10.1212/WNL.0b013e3181dd42b3.
  • 4. Pluta RM, Hansen-Schwartz J, Dreier J, Vajkoczy P, Macdonald RL, Nishizawa Z, et al. Cerebral vasospasm following subarachnoid hemorrhage: time for a new world of thought. Neurol Res. 2009;31(2):151–8. doi: 10.1179/174313209X393564.
  • 5. Barker FG, Heros RC. Clinical aspects of vasospasm. Neurosurg Clin N Am. 1990;1(2):277-288. PMID: 2136141
  • 6. Wang Y, Liu Y, Li Y, Liu B, Wu P, Xu S, et al. Protective effects of astaxanthin on subarachnoid hemorrhage-induced early brain injury: Reduction of cerebral vasospasm and improvement of neuron survival and mitochondrial function. Acta Histochem. 2019;121(1):56-63. doi: 10.1016/j.acthis.2018.10.014.
  • 7. Baggott CD, Aagaard-Kienitz B. Cerebral Vasospasm. Neurosurg Clin N Am. 2014;25(3):497-528. doi: 10.1016/j.nec.2014.04.008.
  • 8. Pluta RM, Afshar JKB, Boock RJ, Oldfield EH. Temporal changes in perivascular concentrations of oxyhemoglobin, deoxyhemoglobin, and methemoglobin after subarachnoid hemorrhage. J Neurosurg. 1998;88(3):557-561. doi: 10.3171/jns.1998.88.3.0557.
  • 9. Bartel DB. MicroRNAs: Genomics, biogenesis, mechanism, and function. Cell. 2004;116(2): 281-297. doi: 10.1016/S0092-8674(04)00045-5.
  • 10. Yu Z, Wang C, Wang M, Li Z, Casimiro MC, Liu M, et al. A cyclin D1/microRNA 17/20 regulatory feedback loop in control of breast cancer cell proliferation. J Cell Biol. 2008;182(3):509-17. doi: 10.1083/jcb.200801079. 11. Sonkoly E, Pivarcsi A. microRNAs in inflammation. Int Rev Immunol. 2009;28(6):535-61. doi: 10.3109/08830180903208303.
  • 12. Gupta P, Bhattacharjee S, Sharma AR, Sharma G, Lee SS, Chakraborty C. miRNAs in Alzheimer Disease. A Therapeutic Perspective. Curr Alzheimer Res. 2017;14(11):1198-1206. doi: 10.2174/1567205014666170829101016.
  • 13. Mogilyansky E, Rigoutsos I. The miR-17/92 cluster: a comprehensive update on its genomics, genetics, functions and increasingly important and numerous roles in health and disease. Cell Death Differ. 2013;20:1603-14. doi: 10.1038/cdd.2013.125.
  • 14. Liu NK, Wang XF, Lu QB, Xu XM: Altered microRNA expression following traumatic spinal cord injury. Exp Neurol. 2009;219(2):424-29. doi: 10.1016/j.expneurol.2009.06.015.
  • 15. Pandi-Perumal SR, Trakht I, Srinivasan V, Spence DW, Maestroni GJ, Zisapel N, et al. Physiological effects of melatonin: role of melatonin receptors and signal transduction pathways. Prog Neurobiol. 2008;85(3):335-53. doi: 10.1016/j.pneurobio.2008.04.001.
  • 16. Cardinali, D. P. Melatonin: clinical perspectives in neurodegeneration. Front Endocrinol (Lausanne). 2019;10:480. doi: 10.3389/fendo.2019.00480.
  • 17. Ding K, Xu J, Wang H, Zhang L, Wu Y, Li T. Melatonin protects the brain from apoptosis by enhancement of autophagy after traumatic brain injury in mice. Neurochem Int. 2015:91:46-54. doi: 10.1016/j.neuint.2015.10.008.
  • 18. Tsai MC, Chen WJ, Tsai MS, Ching CH, Chuang JI. Melatonin attenuates brain contusion-induced oxidative insult, inactivation of signal transducers and activators of transcription 1, and upregulation of suppressor of cytokine signaling-3 in rats. J Pineal Res. 2011;51(2):233-245. doi: 10.1111/j.1600-079X.2011.00885.x.
  • 19. National Research Council (US) Committee for the Update of the Guide for the Care and Use of Laboratory Animals. Guide for the Care and Use of Laboratory Animals. 8th ed. Washington (DC): National Academies Press (US); 2011. doi:10.17226/12910.
  • 20. Prunell GF, Mathiesen T, Svendgaard NA. A new experimental model in rats for study of the pathophysiology of subarachnoid hemorrhage. Neuroreport. 2002;13(18):2553-6. doi: 10.1097/00001756-200212200-00034.
  • 21. Pekince A, Kuzeyli K, Çakır E, Usul H, Karaarslan G, Baykal S, et al. Biochemical and hystopathological effects of H1 receptor blocker, papaverine and nimodipin in experimental cerebral vasospasm. J Turkish Cereb Vasc Dis, 2003:9(1):13-18.
  • 22. Malçok ÜA, Şehitoğlu MH, Büyük B, Sancak EB, Taş Hİ. Protective effect of metformin against lithium-induced cerebral neurotoxicity in rats. Med Science. 2021;10(2):350-5 doi: 10.5455/medscience.2020.12.253.
  • 23. Muehlschlegel S. Subarachnoid Hemorrhage. Continuum (Minneap Minn). 2018;24(6):1623-57. doi: 10.1212/CON.0000000000000679.
  • 24. Al-Khindi T, Macdonald RL, Schweizer TA. Cognitive and functional outcome after aneurysmal subarachnoid hemorrhage. Stroke. 2010;41(8):e519–e536. doi: 10.1161/STROKEAHA.110.581975.
  • 25. Li S, Yang S, Sun B, Hang C. Melatonin attenuates early brain injury after subarachnoid hemorrhage by the JAK-STAT signaling pathway. Int J Clin Exp Pathol. 2019;12(3):909-915. PMID: 31933900
Toplam 24 adet kaynakça vardır.

Ayrıntılar

Birincil Dil İngilizce
Konular Klinik Tıp Bilimleri
Bölüm Araştırma Makalesi
Yazarlar

Başak Büyük 0000-0003-1817-2241

Ümit Ali Malçok 0000-0002-1272-9654

Yayımlanma Tarihi 31 Aralık 2022
Gönderilme Tarihi 1 Ağustos 2022
Kabul Tarihi 29 Ekim 2022
Yayımlandığı Sayı Yıl 2022 Cilt: 6 Sayı: 3

Kaynak Göster

Vancouver Büyük B, Malçok ÜA. Effect of miRs-17/20 on vasospasm in subarachnoid hemorrhage model of rats. Acta Med. Alanya. 2022;6(3):256-62.

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