Research Article
BibTex RIS Cite

Neuroprotective Effect of Paeonol in the Rat Model of Traumatic Brain Injury

Year 2020, Volume: 73 Issue: 1, 42 - 46, 13.05.2020
https://doi.org/10.4274/atfm.galenos.2020.35229

Abstract

Objectives: Traumatic brain injury (TBI) is a major cause of disability and mortality that induces oxidative stress and apoptosis causing cellular damage. Several animal models have shown paeonol to be a powerful antioxidant, antiapoptotic, and neuroprotective substance. This study aimed to investigate possible neuroprotective effects of paeonol in a rat TBI model.

Materials and Methods: Thirty-two male rats were divided into four groups: control, trauma, vehicle, and paeonol groups. Trauma, vehicle, and paeonol groups were subjected to closed-head, contusive weight-drop injuries. The vehicle (saline) or paeonol (50 mg/kg) was orally administered as premedication for 15 days. Brain samples were obtained 24 hours after trauma. Histomorphological evaluation of the cerebral cortex was performed using electron and light microscopy.

Results: Histopathological examination revealed that the TBI-induced cerebral cortex damage was less in the paeonol group.

Conclusion: Paeonol exhibited neuroprotective and anti-edematous effects against TBI.

Ethical Statement

Ethics Committee Approval: Animal care and all experiments were conducted according tothe European Parliament and Council directive 2010/63/EU of September 22, 2010 with regard to the protection of animals for experimental use. Animal ethics committee permission is obtained from The Saki Yenilli Animal Care and Use Committee (0001.01.02). They reviewed and approved all experimental procedures used in this study. Informed Consent: Due to the fact that this study is experiment study, informed consent was not obtained. Peer-review: Internally and externally peer-reviewed.

Supporting Institution

-

Project Number

-

Thanks

-

References

  • 1. Acosta SA, Tajiri N, Shinozuka K, et al. Long-term upregulation of inflammation and suppression of cell proliferation in the brain of adult rats exposed to traumatic brain injury using the controlled cortical impact model. PLoS One. 2013;8:e53376.
  • 2. Lozano D, Gonzales-Portillo GS, Acosta S, et al. Neuroinflammatory responses to traumatic brain injury: etiology, clinical consequences, and therapeutic opportunities. Neuropsychiatr Dis Treat. 2015;11:97-106.
  • 3. Salehi A, Zhang JH, Obenaus A. Response of the cerebral vasculature following traumatic brain injury. J Cereb Blood Flow Metab. 2017;37:2320- 2339.
  • 4. Pop V, Badaut J. A neurovascular perspective for long-term changes after brain trauma. Transl Stroke Res. 2011;2:533-545.
  • 5. Giacino JT, Whyte J, Bagiella E, et al. Placebo-controlled trial of amantadine for severe traumatic brain injury. N Engl J Med. 2012;366:819-826.
  • 6. Kertmen H, Gürer B, Yilmaz ER, et al. Antioxidant and antiapoptotic effects of darbepoetin-α against traumatic brain injury in rats. Arch Med Sci. 2015;11:1119-1128.
  • 7. Özay R, Türkoğlu E, Gürer B, et al. Does Decorin Protect Neuronal Tissue via Its Antioxidant and Antiinflammatory Activity from Traumatic Brain Injury: An Experimental Study.World Neurosurg. 2017;97:407-415.
  • 8. Paglia DE, Valentine WN. Studies on the quantitative and qualitative characterization of erythrocyte glutathione peroxidase. J Lab Clin Med. 1967;70:158-169.
  • 9. Yilmaz ER, Kertmen H, Gürer B, et al. The protective effect of 2-mercaptoethane sulfonate (MESNA) against traumatic brain injury in rats. ActaNeurochir (Wien)2013;155:141-149; discussion 149.
  • 10. Perez-Polo JR, Rea HC, Johnson KM, et al. Inflammatory consequences in a rodent model of mild traumatic brain injury. J Neurotrauma. 2013;30:727- 740.
  • 11. Özay R, Türkoğlu ME, Gürer B, et al. The Protective Effect of Omeprazole Against Traumatic Brain Injury: An Experimental Study. World Neurosurg. 2017;104:634-643.
  • 12. Wu JB, Song NN, Wei XB, et al. Protective effects of paeonol on cultured rat hippocampal neurons against oxygen-glucose deprivation-induced injury. J Neurol Sci. 2008;264:50-55.
  • 13. Zhong SZ, Ge QH, Qu R, et al. Paeonol attenuates neurotoxicity and ameliorates cognitive impairment induced by d-galactose in ICR mice. J Neurol Sci. 2009; 277:58-64.
  • 14. Jin H, Wang M, Wang J, et al. Paeonol attenuates isoflurane anesthesiainduced hippocampal neurotoxicity via modulation of JNK/ERK/P38MAPK pathway and regulates histone acetylation in neonatal rat. J Matern Fetal Neonatal Med. 2018;29:1-11.
  • 15. Liu MH, Lin AH, Lee HF, et al. Paeonol attenuates cigarette smoke-induced lung inflammation by inhibiting ROS-sensitive inflammatory signaling. Mediators Inflamm. 2014;2014:651890.
  • 16. Choy KW, Lau YS, Murugan D, et al. Chronic treatment with paeonol improves endothelial function in mice through inhibition of endoplasmic reticulum stress-mediated oxidative stress. PLoS One. 2017;12:e0178365.
  • 17. Ding Y, Li Q, Xu Y, et al. Attenuating Oxidative Stress by Paeonol Protected against Acetaminophen-Induced Hepatotoxicity in Mice. PLoS One. 2016;11:e0154375.
  • 18. Marmarou A, Foda MA, van den Brink W, et al. A new model of diffuse brain injury in rats. Part I: Pathophysiology and biomechanics. J Neurosurg. 1994;80:291-300.
  • 19. Ucar T, Tanriover G, Gurer I, et al. Modified experimental mild traumatic brain injury model. J Trauma. 2006;60:558-565.
  • 20. Maas AIR, Menon DK, Adelson PD, et al. Traumatic brain injury: integrated approaches to improve prevention, clinical care, and research. Lancet Neurol. 2017; 16:987-1048.
  • 21. Yasuda T, Kon R, Nakazawa T, et al. Metabolism of paeonol in rats. J Nat Prod. 1999; 62:1142-1144.
  • 22. Ma LY, Xu XD, Zhang Q, et al. Paeonol pharmacokinetics in the rat following i.m. administration. Eur J Drug MetabPharmacokinet. 2008;33:133-136.
  • 23. Zhao Y, Fu B, Zhang X, et al. Paeonol pretreatment attenuates cerebral ischemic injury via upregulating expression of pAkt, Nrf2, HO-1 and ameliorating BBB permeability in mice. Brain Res Bull. 2014; 109:61-67.
  • 24. Zhong SZ, Ge QH, Qu R, et al. Paeonol attenuates neurotoxicity and ameliorates cognitive impairment induced by d-galactose in ICR mice. J Neurol Sci. 2009; 277:58-64.
  • 25. Hsieh CL, Cheng CY, Tsai TH, et al. Paeonol reduced cerebral infarction involving the superoxide anion and microglia activation in ischemiareperfusion injured rats. J Ethnopharmacol. 2006;106:208-215.
  • 26. Zhao B, Shi QJ, Zhang ZZ, et al. Protective effects of paeonol on subacute/ chronic brain injury during cerebral ischemia in rats. ExpTher Med. 2018;15:3836-3846.
  • 27. Liao WY, Tsai TH, Ho TY, et al. Neuroprotective Effect of Paeonol Mediates Anti-Inflammation via Suppressing Toll-Like Receptor 2 and Toll-Like Receptor 4 Signaling Pathways in Cerebral Ischemia-Reperfusion Injured Rats. Evid Based Complement Alternat Med. 2016;2016:3704647.

Rat Travmatik Beyin Hasarı Modelinde Paeonol’ün Nöroprotektif Etkisi

Year 2020, Volume: 73 Issue: 1, 42 - 46, 13.05.2020
https://doi.org/10.4274/atfm.galenos.2020.35229

Abstract

Amaç: Travmatik beyin hasarı (TBH), oksidatif stres ve hücresel hasara neden olan apoptozu indükleyen temel bir sakatlık ve ölüm nedenidir. Bazı hayvan modelleri paeonolün güçlü bir antioksidan, antiapoptotik ve nöroprotektif madde olduğunu göstermiştir. Bu çalışma, paeonolün rat TBI modelinde olası nöroprotektif etkilerini araştırmayı amaçlamıştır.

Gereç ve Yöntemler: Otuz iki erkek rat dört gruba ayrıldı: kontrol, travma, taşıyıcı ve paeonol. Travma, taşıyıcı ve paeonol gruplarında kapalı kafa travması ağırlık düşürülerek uygulandı. Taşıyıcı (serum fizyolojik) veya paeonol (50 mg/kg) 15 gün boyunca premedikasyon olarak oral yoldan uygulandı. Beyin örnekleri travmadan 24 saat sonra alındı. Serebral korteksin histomorfolojik değerlendirmesi elektron ve ışık mikroskopisi kullanılarak yapıldı.

Bulgular: Histopatolojik incelemede, paeonol grubunda TBH kaynaklı serebral korteks hasarının daha az olduğu görüldü. Sonuç: Paeonol, TBI’ya karşı nöroprotektif ve antiödematöz etkiler sergilemiştir.

Ethical Statement

-

Supporting Institution

-

Project Number

-

Thanks

-

References

  • 1. Acosta SA, Tajiri N, Shinozuka K, et al. Long-term upregulation of inflammation and suppression of cell proliferation in the brain of adult rats exposed to traumatic brain injury using the controlled cortical impact model. PLoS One. 2013;8:e53376.
  • 2. Lozano D, Gonzales-Portillo GS, Acosta S, et al. Neuroinflammatory responses to traumatic brain injury: etiology, clinical consequences, and therapeutic opportunities. Neuropsychiatr Dis Treat. 2015;11:97-106.
  • 3. Salehi A, Zhang JH, Obenaus A. Response of the cerebral vasculature following traumatic brain injury. J Cereb Blood Flow Metab. 2017;37:2320- 2339.
  • 4. Pop V, Badaut J. A neurovascular perspective for long-term changes after brain trauma. Transl Stroke Res. 2011;2:533-545.
  • 5. Giacino JT, Whyte J, Bagiella E, et al. Placebo-controlled trial of amantadine for severe traumatic brain injury. N Engl J Med. 2012;366:819-826.
  • 6. Kertmen H, Gürer B, Yilmaz ER, et al. Antioxidant and antiapoptotic effects of darbepoetin-α against traumatic brain injury in rats. Arch Med Sci. 2015;11:1119-1128.
  • 7. Özay R, Türkoğlu E, Gürer B, et al. Does Decorin Protect Neuronal Tissue via Its Antioxidant and Antiinflammatory Activity from Traumatic Brain Injury: An Experimental Study.World Neurosurg. 2017;97:407-415.
  • 8. Paglia DE, Valentine WN. Studies on the quantitative and qualitative characterization of erythrocyte glutathione peroxidase. J Lab Clin Med. 1967;70:158-169.
  • 9. Yilmaz ER, Kertmen H, Gürer B, et al. The protective effect of 2-mercaptoethane sulfonate (MESNA) against traumatic brain injury in rats. ActaNeurochir (Wien)2013;155:141-149; discussion 149.
  • 10. Perez-Polo JR, Rea HC, Johnson KM, et al. Inflammatory consequences in a rodent model of mild traumatic brain injury. J Neurotrauma. 2013;30:727- 740.
  • 11. Özay R, Türkoğlu ME, Gürer B, et al. The Protective Effect of Omeprazole Against Traumatic Brain Injury: An Experimental Study. World Neurosurg. 2017;104:634-643.
  • 12. Wu JB, Song NN, Wei XB, et al. Protective effects of paeonol on cultured rat hippocampal neurons against oxygen-glucose deprivation-induced injury. J Neurol Sci. 2008;264:50-55.
  • 13. Zhong SZ, Ge QH, Qu R, et al. Paeonol attenuates neurotoxicity and ameliorates cognitive impairment induced by d-galactose in ICR mice. J Neurol Sci. 2009; 277:58-64.
  • 14. Jin H, Wang M, Wang J, et al. Paeonol attenuates isoflurane anesthesiainduced hippocampal neurotoxicity via modulation of JNK/ERK/P38MAPK pathway and regulates histone acetylation in neonatal rat. J Matern Fetal Neonatal Med. 2018;29:1-11.
  • 15. Liu MH, Lin AH, Lee HF, et al. Paeonol attenuates cigarette smoke-induced lung inflammation by inhibiting ROS-sensitive inflammatory signaling. Mediators Inflamm. 2014;2014:651890.
  • 16. Choy KW, Lau YS, Murugan D, et al. Chronic treatment with paeonol improves endothelial function in mice through inhibition of endoplasmic reticulum stress-mediated oxidative stress. PLoS One. 2017;12:e0178365.
  • 17. Ding Y, Li Q, Xu Y, et al. Attenuating Oxidative Stress by Paeonol Protected against Acetaminophen-Induced Hepatotoxicity in Mice. PLoS One. 2016;11:e0154375.
  • 18. Marmarou A, Foda MA, van den Brink W, et al. A new model of diffuse brain injury in rats. Part I: Pathophysiology and biomechanics. J Neurosurg. 1994;80:291-300.
  • 19. Ucar T, Tanriover G, Gurer I, et al. Modified experimental mild traumatic brain injury model. J Trauma. 2006;60:558-565.
  • 20. Maas AIR, Menon DK, Adelson PD, et al. Traumatic brain injury: integrated approaches to improve prevention, clinical care, and research. Lancet Neurol. 2017; 16:987-1048.
  • 21. Yasuda T, Kon R, Nakazawa T, et al. Metabolism of paeonol in rats. J Nat Prod. 1999; 62:1142-1144.
  • 22. Ma LY, Xu XD, Zhang Q, et al. Paeonol pharmacokinetics in the rat following i.m. administration. Eur J Drug MetabPharmacokinet. 2008;33:133-136.
  • 23. Zhao Y, Fu B, Zhang X, et al. Paeonol pretreatment attenuates cerebral ischemic injury via upregulating expression of pAkt, Nrf2, HO-1 and ameliorating BBB permeability in mice. Brain Res Bull. 2014; 109:61-67.
  • 24. Zhong SZ, Ge QH, Qu R, et al. Paeonol attenuates neurotoxicity and ameliorates cognitive impairment induced by d-galactose in ICR mice. J Neurol Sci. 2009; 277:58-64.
  • 25. Hsieh CL, Cheng CY, Tsai TH, et al. Paeonol reduced cerebral infarction involving the superoxide anion and microglia activation in ischemiareperfusion injured rats. J Ethnopharmacol. 2006;106:208-215.
  • 26. Zhao B, Shi QJ, Zhang ZZ, et al. Protective effects of paeonol on subacute/ chronic brain injury during cerebral ischemia in rats. ExpTher Med. 2018;15:3836-3846.
  • 27. Liao WY, Tsai TH, Ho TY, et al. Neuroprotective Effect of Paeonol Mediates Anti-Inflammation via Suppressing Toll-Like Receptor 2 and Toll-Like Receptor 4 Signaling Pathways in Cerebral Ischemia-Reperfusion Injured Rats. Evid Based Complement Alternat Med. 2016;2016:3704647.
There are 27 citations in total.

Details

Primary Language English
Subjects Brain and Nerve Surgery (Neurosurgery), Anaesthesiology, Histology and Embryology
Journal Section Research Article
Authors

Emine Arık This is me 0000-0001-6596-3578

Habibullah Dolgun 0000-0002-1513-2044

Pınar Kuru Bektaşoğlu 0000-0001-9889-9955

Julide Ergil 0000-0002-4580-7866

Banu Coşkun 0000-0002-7723-9146

Çağhan Tönge 0000-0002-9921-1750

Özden Çağlar Öztürk This is me 0000-0003-3964-1895

Levent Gürses This is me 0000-0003-3513-9478

Bora Gürer 0000-0003-1500-6184

Project Number -
Publication Date May 13, 2020
Published in Issue Year 2020 Volume: 73 Issue: 1

Cite

APA Arık, E., Dolgun, H., Kuru Bektaşoğlu, P., … Ergil, J. (2020). Neuroprotective Effect of Paeonol in the Rat Model of Traumatic Brain Injury. Ankara Üniversitesi Tıp Fakültesi Mecmuası, 73(1), 42-46. https://doi.org/10.4274/atfm.galenos.2020.35229
AMA Arık E, Dolgun H, Kuru Bektaşoğlu P, et al. Neuroprotective Effect of Paeonol in the Rat Model of Traumatic Brain Injury. Ankara Üniversitesi Tıp Fakültesi Mecmuası. May 2020;73(1):42-46. doi:10.4274/atfm.galenos.2020.35229
Chicago Arık, Emine, Habibullah Dolgun, Pınar Kuru Bektaşoğlu, Julide Ergil, Banu Coşkun, Çağhan Tönge, Özden Çağlar Öztürk, Levent Gürses, and Bora Gürer. “Neuroprotective Effect of Paeonol in the Rat Model of Traumatic Brain Injury”. Ankara Üniversitesi Tıp Fakültesi Mecmuası 73, no. 1 (May 2020): 42-46. https://doi.org/10.4274/atfm.galenos.2020.35229.
EndNote Arık E, Dolgun H, Kuru Bektaşoğlu P, Ergil J, Coşkun B, Tönge Ç, Öztürk ÖÇ, Gürses L, Gürer B (May 1, 2020) Neuroprotective Effect of Paeonol in the Rat Model of Traumatic Brain Injury. Ankara Üniversitesi Tıp Fakültesi Mecmuası 73 1 42–46.
IEEE E. Arık, H. Dolgun, P. Kuru Bektaşoğlu, J. Ergil, B. Coşkun, Ç. Tönge, Ö. Ç. Öztürk, L. Gürses, and B. Gürer, “Neuroprotective Effect of Paeonol in the Rat Model of Traumatic Brain Injury”, Ankara Üniversitesi Tıp Fakültesi Mecmuası, vol. 73, no. 1, pp. 42–46, 2020, doi: 10.4274/atfm.galenos.2020.35229.
ISNAD Arık, Emine et al. “Neuroprotective Effect of Paeonol in the Rat Model of Traumatic Brain Injury”. Ankara Üniversitesi Tıp Fakültesi Mecmuası 73/1 (May2020), 42-46. https://doi.org/10.4274/atfm.galenos.2020.35229.
JAMA Arık E, Dolgun H, Kuru Bektaşoğlu P, Ergil J, Coşkun B, Tönge Ç, Öztürk ÖÇ, Gürses L, Gürer B. Neuroprotective Effect of Paeonol in the Rat Model of Traumatic Brain Injury. Ankara Üniversitesi Tıp Fakültesi Mecmuası. 2020;73:42–46.
MLA Arık, Emine et al. “Neuroprotective Effect of Paeonol in the Rat Model of Traumatic Brain Injury”. Ankara Üniversitesi Tıp Fakültesi Mecmuası, vol. 73, no. 1, 2020, pp. 42-46, doi:10.4274/atfm.galenos.2020.35229.
Vancouver Arık E, Dolgun H, Kuru Bektaşoğlu P, Ergil J, Coşkun B, Tönge Ç, et al. Neuroprotective Effect of Paeonol in the Rat Model of Traumatic Brain Injury. Ankara Üniversitesi Tıp Fakültesi Mecmuası. 2020;73(1):42-6.