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Protective effects of paeonol on subacute/chronic brain injury during cerebral ischemia in rats

  • Authors:
    • Bing Zhao
    • Qiao‑Juan Shi
    • Zhen‑Zhong Zhang
    • Shu‑Yan Wang
    • Xi Wang
    • Hao Wang
  • View Affiliations / Copyright

    Affiliations: Department of Anesthesiology, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310013, P.R. China , Department of Neurology, Tongde Hospital of Zhejiang Province, Hangzhou, Zhejiang 310012, P.R. China, Key Laboratory of Digestive Pathophysiology of Zhejiang Province, Zhejiang Hospital of Traditional Chinese Medicine, Zhejiang Chinese Medical University, Hangzhou, Zhejiang 310006, P.R. China
    Copyright: © Zhao et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 3836-3846
    |
    Published online on: February 26, 2018
       https://doi.org/10.3892/etm.2018.5893
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Abstract

Ischemic stroke is a highly complex pathological process that is divided into acute, subacute and chronic phases. Paeonol is a biologically active natural product with a variety of pharmacological effects, including those on neuronal activity. However, the effects of paeonol on subacute/chronic ischemic stroke have remained to be elucidated. The present study was designed to investigate the effects of paeonol against subacute and chronic cerebral ischemic injury and to explore the possible underlying mechanisms. Male adult Sprague Dawley rats were randomly divided into a sham group (treated with saline), a model group [subjected to middle cerebral artery occlusion (MCAO) and treated with saline] and a paeonol‑treated group (MCAO + paeonol at 25 mg/kg). Behavioral impairment, infarct volume and ischemic/contralateral hemispheric ratios were assessed at 72 h and at 28 days after MCAO, respectively. Immunofluorescence was employed to determine the neuronal damage and glial responses after MCAO. Compared with the model group, paeonol treatment significantly attenuated behavioral impairment, ischemic infarct volume and moderate cerebral edema in the ischemic brain at 72 h, as well as brain atrophy at 28 days after reperfusion. Furthermore, paeonol treatment ameliorated neuronal damage in the ischemic core and boundary zone regions at 72 h after reperfusion and in the boundary zone at 28 days after reperfusion. In addition, paeonol treatment reduced the proliferation of astrocytes in the boundary zone, and inhibited microglial activation in the ischemic core and boundary zone regions at 72 h and 28 days after reperfusion. These results demonstrated the protective effects of paeonol against subacute/chronic cerebral ischemia, and the mechanism of action may include subacute/chronic microglial activation and astrocyte proliferation.
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View References

1 

Hankey GJ: Stroke. Lancet. 389:641–654. 2017. View Article : Google Scholar : PubMed/NCBI

2 

Jauch EC, Saver JL, Adams HP Jr, Bruno A, Connors JJ, Demaerschalk BM, Khatri P, McMullan PW Jr, Qureshi AI, Rosenfield K, et al: Guidelines for the early management of patients with acute ischemic stroke: A guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke. 44:870–947. 2013. View Article : Google Scholar : PubMed/NCBI

3 

Li L and Stary CM: Targeting glial mitochondrial function for protection from cerebral ischemia: Relevance, mechanisms, and the role of MicroRNAs. Oxid Med Cell Longev. 2016:60323062016. View Article : Google Scholar : PubMed/NCBI

4 

Hacke W, Kaste M, Bluhmki E, Brozman M, Dávalos A, Guidetti D, Larrue V, Lees KR, Medeghri Z, Machnig T, et al: Thrombolysis with alteplase 3 to 4.5 h after acute ischemic stroke. N Engl J Med. 359:1317–1329. 2008. View Article : Google Scholar : PubMed/NCBI

5 

Shichita T, Ago T, Kamouchi M, Kitazono T, Yoshimura A and Ooboshi H: Novel therapeutic strategies targeting innate immune responses and early inflammation after stroke. J Neurochem. 123 Suppl 2:S29–S38. 2012. View Article : Google Scholar

6 

Fagan SC, Hess DC, Hohnadel EJ, Pollock DM and Ergul A: Targets for vascular protection after acute ischemic stroke. Stroke. 35:2220–2225. 2004. View Article : Google Scholar : PubMed/NCBI

7 

Burda JE and Sofroniew MV: Reactive gliosis and the multicellular response to CNS damage and disease. Neuron. 81:229–248. 2014. View Article : Google Scholar : PubMed/NCBI

8 

Hanisch UK and Kettenmann H: Microglia: Active sensor and versatile effector cells in the normal and pathologic brain. Nat Neurosci. 10:1387–1394. 2007. View Article : Google Scholar : PubMed/NCBI

9 

Zhao B, Zhao CZ, Zhang XY, Huang XQ, Shi WZ, Fang SH, Lu YB, Zhang WP, Xia Q and Wei EQ: The new P2Y-like receptor G protein-coupled receptor 17 mediates acute neuronal injury and late microgliosis after focal cerebral ischemia in rats. Neuroscience. 202:42–57. 2012. View Article : Google Scholar : PubMed/NCBI

10 

Choudhury GR and Ding S: Reactive astrocytes and therapeutic potential in focal ischemic stroke. Neurobiol Dis. 85:234–244. 2016. View Article : Google Scholar : PubMed/NCBI

11 

Liu Z and Chopp M: Astrocytes, therapeutic targets for neuroprotection and neurorestoration in ischemic stroke. Prog Neurobiol. 144:103–120. 2016. View Article : Google Scholar : PubMed/NCBI

12 

Kim JY, Kim N and Yenari MA: Mechanisms and potential therapeutic applications of microglial activation after brain injury. CNS Neurosci Ther. 21:309–319. 2015. View Article : Google Scholar : PubMed/NCBI

13 

Jin X and Yamashita T: Microglia in central nervous system repair after injury. J Biochem. 159:491–496. 2016. View Article : Google Scholar : PubMed/NCBI

14 

Bu Y, Lee K, Jung HS and Moon SK: Therapeutic effects of traditional herbal medicine on cerebral ischemia: A perspective of vascular protection. Chin J Integr Med. 19:804–814. 2013. View Article : Google Scholar : PubMed/NCBI

15 

Ding Y, Li Q, Xu Y, Chen Y, Deng Y, Zhi F and Qian K: Attenuating oxidative stress by paeonol protected against Acetaminophen-induced hepatotoxicity in mice. PLoS One. 11:e01543752016. View Article : Google Scholar : PubMed/NCBI

16 

Liu YR, Chen JJ and Dai M: Paeonol protects rat vascular endothelial cells from ox-LDL-induced injury in vitro via downregulating microRNA-21 expression and TNF-α release. Acta Pharmacol Sin. 35:483–488. 2014. View Article : Google Scholar : PubMed/NCBI

17 

Li M, Tan SY and Wang XF: Paeonol exerts an anticancer effect on human colorectal cancer cells through inhibition of PGE, synthesis and COX-2 expression. Oncol Rep. 32:2845–2853. 2014. View Article : Google Scholar : PubMed/NCBI

18 

Liu J, Feng L, Ma D, Zhang M, Gu J, Wang S, Fu Q, Song Y, Lan Z, Qu R and Ma S: Neuroprotective effect of paeonol on cognition deficits of diabetic encephalopathy in streptozotocin-induced diabetic rat. Neurosci Lett. 549:63–68. 2013. View Article : Google Scholar : PubMed/NCBI

19 

Liao WY, Tsai TH, Ho TY, Lin YW, Cheng CY and Hsieh CL: 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. 2016:37046472016. View Article : Google Scholar : PubMed/NCBI

20 

Zhao Y, Fu B, Zhang X, Zhao T, Chen L, Zhang J and Wang X: Paeonol pretreatment attenuates cerebral ischemic injury via upregulating expression of pAkt, Nrf2, HO-1 and ameliorating BBB permeability in mice. Brain Res Bull. 109:61–67. 2014. View Article : Google Scholar : PubMed/NCBI

21 

Shi X, Chen YH, Liu H and Qu HD: Therapeutic effects of paeonol on methyl-4-phenyl-1,2,3,6-tetrahydropyridine/probenecid-induced Parkinson's disease in mice. Mol Med Rep. 14:2397–2404. 2016. View Article : Google Scholar : PubMed/NCBI

22 

Zhou A, Wu H, Pan J, Wang X, Li J, Wu Z and Hui A: Synthesis and evaluation of paeonol derivatives as potential multifunctional agents for the treatment of Alzheimer's disease. Molecules. 20:1304–1318. 2015. View Article : Google Scholar : PubMed/NCBI

23 

Longa EZ, Weinstein PR, Carlson S and Cummins R: Reversible middle cerebral artery occlusion without craniectomy in rats. Stroke. 20:84–91. 1989. View Article : Google Scholar : PubMed/NCBI

24 

Shi QJ, Wang H, Liu ZX, Fang SH, Song XM, Lu YB, Zhang WP, Sa XY, Ying HZ and Wei EQ: HAMI 3379, a CysLT2R antagonist, dose- and time-dependently attenuates brain injury and inhibits microglial inflammation after focal cerebral ischemia in rats. Neuroscience. 291:53–69. 2015. View Article : Google Scholar : PubMed/NCBI

25 

Yano T, Anraku S, Nakayama R and Ushijima K: Neuroprotective effect of urinary trypsin inhibitor against focal cerebral ischemia-reperfusion injury in rats. Anesthesiology. 98:465–473. 2003. View Article : Google Scholar : PubMed/NCBI

26 

Graham SM, McCullough LD and Murphy SJ: Animal models of ischemic stroke: Balancing experimental aims and animal care. Comp Med. 54:486–496. 2004.PubMed/NCBI

27 

Rewell SS, Churilov L, Sidon TK, Aleksoska E, Cox SF, Macleod MR and Howells DW: Evolution of ischemic damage and behavioural deficit over 6 months after MCAo in the rat: Selecting the optimal outcomes and statistical power for multi-centre preclinical trials. PLoS One. 12:e01716882017. View Article : Google Scholar : PubMed/NCBI

28 

Yonemori F, Yamaguchi T, Yamada H and Tamura A: Evaluation of a motor deficit after chronic focal cerebral ischemia in rats. J Cereb Blood Flow Metab. 18:1099–1106. 1998. View Article : Google Scholar : PubMed/NCBI

29 

Lu LQ, Lou Q, Guo HG, Zhou WW, Ying HZ, Wei EQ and Shi QJ: Neuroprotective effect of HAMI 3379, a CysLT2R receptor antagonist, on chronic brain injury after focal cerebral ischemia in rats. Int J Clin Exp Pathol. 10:4123–4136. 2017.

30 

Shen LH, Li Y, Chen J, Cui Y, Zhang C, Kapke A, Lu M, Savant-Bhonsale S and Chopp M: One-year follow-up after bone marrow stromal cell treatment in middle-aged female rats with stroke. Stroke. 38:2150–2156. 2007. View Article : Google Scholar : PubMed/NCBI

31 

Garbuzova-Davis S, Haller E, Tajiri N, Thomson A, Barretta J, Williams SN, Haim ED, Qin H, Frisina-Deyo A, Abraham JV, et al: Blood-spinal cord barrier alterations in subacute and chronic Stages of a rat model of focal cerebral ischemia. J Neuropathol Exp Neurol. 75:673–688. 2016. View Article : Google Scholar : PubMed/NCBI

32 

Ma Y, Wang J, Wang Y and Yang GY: The biphasic function of microglia in ischemic stroke. Prog Neurobiol. 157:247–272. 2017. View Article : Google Scholar : PubMed/NCBI

33 

Xu L, He D and Bai Y: Microglia-mediated inflammation and neurodegenerative disease. Mol Neurobiol. 53:6709–6715. 2016. View Article : Google Scholar : PubMed/NCBI

34 

Benarroch EE: Microglia: Multiple roles in surveillance, circuit shaping, and response to injury. Neurology. 81:1079–1088. 2013. View Article : Google Scholar : PubMed/NCBI

35 

Lee Y, Lee SR, Choi SS, Yeo HG, Chang KT and Lee HJ: Therapeutically targeting neuroinflammation and microglia after acute ischemic stroke. Biomed Res Int. 2014:2972412014. View Article : Google Scholar : PubMed/NCBI

36 

Kawabori M and Yenari MA: The role of the microglia in acute CNS injury. Metab Brain Dis. 30:381–392. 2015. View Article : Google Scholar : PubMed/NCBI

37 

Nam KN, Woo BC, Moon SK, Park SU, Park JY, Hwang JW, Bae HS, Ko CN and Lee EH: Paeonol attenuates inflammation-mediated neurotoxicity and microglial activation. Neural Regen Res. 8:1637–1643. 2013.PubMed/NCBI

38 

Himaya SW, Ryu B, Qian ZJ and Kim SK: Paeonol from Hippocampus kuda Bleeler suppressed the neuro-inflammatory responses in vitro via NF-kB and MAPK signaling pathways. Toxicol In Vitro. 26:878–887. 2012. View Article : Google Scholar : PubMed/NCBI

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Copy and paste a formatted citation
Spandidos Publications style
Zhao B, Shi QJ, Zhang ZZ, Wang SY, Wang X and Wang H: Protective effects of paeonol on subacute/chronic brain injury during cerebral ischemia in rats. Exp Ther Med 15: 3836-3846, 2018.
APA
Zhao, B., Shi, Q., Zhang, Z., Wang, S., Wang, X., & Wang, H. (2018). Protective effects of paeonol on subacute/chronic brain injury during cerebral ischemia in rats. Experimental and Therapeutic Medicine, 15, 3836-3846. https://doi.org/10.3892/etm.2018.5893
MLA
Zhao, B., Shi, Q., Zhang, Z., Wang, S., Wang, X., Wang, H."Protective effects of paeonol on subacute/chronic brain injury during cerebral ischemia in rats". Experimental and Therapeutic Medicine 15.4 (2018): 3836-3846.
Chicago
Zhao, B., Shi, Q., Zhang, Z., Wang, S., Wang, X., Wang, H."Protective effects of paeonol on subacute/chronic brain injury during cerebral ischemia in rats". Experimental and Therapeutic Medicine 15, no. 4 (2018): 3836-3846. https://doi.org/10.3892/etm.2018.5893
Copy and paste a formatted citation
x
Spandidos Publications style
Zhao B, Shi QJ, Zhang ZZ, Wang SY, Wang X and Wang H: Protective effects of paeonol on subacute/chronic brain injury during cerebral ischemia in rats. Exp Ther Med 15: 3836-3846, 2018.
APA
Zhao, B., Shi, Q., Zhang, Z., Wang, S., Wang, X., & Wang, H. (2018). Protective effects of paeonol on subacute/chronic brain injury during cerebral ischemia in rats. Experimental and Therapeutic Medicine, 15, 3836-3846. https://doi.org/10.3892/etm.2018.5893
MLA
Zhao, B., Shi, Q., Zhang, Z., Wang, S., Wang, X., Wang, H."Protective effects of paeonol on subacute/chronic brain injury during cerebral ischemia in rats". Experimental and Therapeutic Medicine 15.4 (2018): 3836-3846.
Chicago
Zhao, B., Shi, Q., Zhang, Z., Wang, S., Wang, X., Wang, H."Protective effects of paeonol on subacute/chronic brain injury during cerebral ischemia in rats". Experimental and Therapeutic Medicine 15, no. 4 (2018): 3836-3846. https://doi.org/10.3892/etm.2018.5893
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