Minocycline conducted microglia phenotype transformation attenuates early brain injury in rats after ischemia stroke

Bo hang; Jun Tang; Jianbo Zhang; Liming Yang; Zhi Chen; Yunfeng Yang; Gang Zhu

doi:10.16016/j.1000-5404.201702080

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Minocycline conducted microglia phenotype transformation attenuates early brain injury in rats after ischemia stroke

更新时间：2026-01-09

- Minocycline conducted microglia phenotype transformation attenuates early brain injury in rats after ischemia stroke
- Journal of Third Military Medical University Vol. 39, Issue 11, Pages: 1105-1111(2017)
- 作者机构：
- 作者简介：
- 基金信息：
  
  the General Program of National Natural Science Foundation of China(81571116);the National Natural Science Foundation of China(81371440);the National Basic Research and Development Program(973计划);the National Basic Research Program(2014CB541606)
- DOI：10.16016/j.1000-5404.201702080
  CLC：
- Received：16 February 2017，
  
  Published：15 June 2017
- 稿件说明：
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Bo hang, Jun Tang, Jianbo Zhang, et al. Minocycline conducted microglia phenotype transformation attenuates early brain injury in rats after ischemia stroke[J]. Journal of Third Military Medical University, 2017, 39(11): 1105-1111.
DOI：

Bo hang, Jun Tang, Jianbo Zhang, et al. Minocycline conducted microglia phenotype transformation attenuates early brain injury in rats after ischemia stroke[J]. Journal of Third Military Medical University, 2017, 39(11): 1105-1111. DOI： 10.16016/j.1000-5404.201702080.

摘要

Abstract

Objective

To investigate the early pathophysical characteristics of ischemic brain injury in rats

and explore the neuroprotective effects on the injury and possible involved molecular mechanisms.

Methods

Middle cerebral artery occlusion (MCAO) was performed in rats using a nylon suture to establish rat model of ischemic brain injury. In 6 and 24 h after MCAO

minocycline was injected intraperitoneally. Triphenyl tetrazolium chloride (TTC) staining was used to detect the infarct volume

and Tunel staining and Nissl staining were used to observe the apoptotic neurons. Immunohistochemical assay was used to detect microglial phenotype

and Western blot assay was employed to detect the expression of apoptosis pathway protein NF-κB. Morris water maze test was adopted to exam the long-term learning memory after MCAO and minocycline administration in 28 d after surgery.

Results

Minocycline administration significantly reduced brain infarct volume in 6 h after MCAO (43.0±5.3

36.0±6.8 cm

0.01)

decreased the apoptotic cerebral neurons and promoted M2 microglia proliferation. However

minocycline given in 24 h after MCAO had no protective effect on infarct volume and neuron apoptosis (

0.05). In addition

minocycline decreased NF-κB protein expression in 6 h after MCAO (

0.01). The learning and memory abilities were obviously lower in the rats after 28 d of MCAO

which could be notably improved by minocycline treatment (

0.01). But such neuroprotective effects were not observed in the rats treated 24 h after MCAO (

0.05).

Conclusion

Minocycline i

mproves memory deficits induced by early ischemic stroke

via

M2 microglial transformation and suppression of apoptosis signal pathway

and attenuates cerebral ischemia-induced neurological inflammation and apoptosis

so as to improve learning and memory function in rats.

关键词

Keywords

references

王拥军张苏明中国缺血性脑卒中和短暂性脑缺血发作二级预防指南2010 中华神经科杂志 2010 43 2 154 160 10.3760/cma.j.issn.1006-7876.2010.02.023 王拥军, 张苏明.中国缺血性脑卒中和短暂性脑缺血发作二级预防指南2010[J].中华神经科杂志, 2010, 43(2):154-160. DOI: 10. 3760/ cma. j. issn.1006-7876. 2010.02.023.

Wang Y J Zhang S M Guidelines for the second level prevention of ischemic stroke and transient ischemic attack in China 2010 Chin J Neurol 2010 43 2 154 160 10.3760/cma.j.issn.1006-7876.2010.02.023 Wang Y J, Zhang S M. Guidelines for the second level prevention of ischemic stroke and transient ischemic attack in China 2010[J]. Chin J Neurol, 2010, 43(2):154-160. DOI: 10.3760/cma.j.issn.1006-7876.2010.02.023.

Chamorro á Dirnagl U Urra X Neuroprotection in acute stroke: targeting excitotoxicity, oxidative and nitrosative stress, and inflammation Lancet Neurol 2016 15 8 869 881 10.1016/S1474-4422(16)00114-9 Chamorro á, Dirnagl U, Urra X, et al . Neuroprotection in acute stroke: targeting excitotoxicity, oxidative and nitrosative stress, and inflammation[J ] . Lancet Neurol, 2016, 15(8): 869-881. DOI:10.1016/S1474-4422(16)00114-9.

Tang J Chen Q Guo J Minocycline Attenuates Neonatal Germinal-Matrix-Hemorrhage-Induced Neuroinflammation and Brain Edema by Activating Cannabinoid Receptor 2 Mol Neurobiol 2016 53 3 1935 1948 10.1007/s12035-015-9154-x Tang J, Chen Q, Guo J, et al . Minocycline Attenuates Neonatal Germinal-Matrix-Hemorrhage-Induced Neuroinflammation and Brain Edema by Activating Cannabinoid Receptor 2[J ] . Mol Neurobiol, 2016, 53(3): 1935-1948. DOI:10.1007/s12035-015-9154-x.

Wu Z Zou X Zhu W Minocycline is effective in intracerebral hemorrhage by inhibition of apoptosis and autophagy J Neurol Sci 2016 371 88 95 10.1016/j.jns.2016.10.025 Wu Z, Zou X, Zhu W, et al . Minocycline is effective in intracerebral hemorrhage by inhibition of apoptosis and autophagy[J ] . J Neurol Sci, 2016, 371: 88-95. DOI:10.1016/j.jns.2016.10.025.

Lopez-Rodriguez A B Siopi E Finn D P CB1 and CB2 cannabinoid receptor antagonists prevent minocycline-induced neuroprotection following traumatic brain injury in mice Cereb Cortex 2015 25 1 35 45 10.1093/cercor/bht202 Lopez-Rodriguez A B, Siopi E, Finn D P, et al . CB1 and CB2 cannabinoid receptor antagonists prevent minocycline-induced neuroprotection following traumatic brain injury in mice[J ] . Cereb Cortex, 2015, 25(1): 35-45. DOI:10.1093/cercor/bht202.

Yrjänheikki J Tikka T Keinänen R A tetracycline derivative, minocycline, reduces inflammation and protects against focal cerebral ischemia with a wide therapeutic window Proc Natl Acad Sci U S A 1999 96 23 13496 13500 10.1073/pnas.96.23.13496 Yrjänheikki J, Tikka T, Keinänen R, et al . A tetracycline derivative, minocycline, reduces inflammation and protects against focal cerebral ischemia with a wide therapeutic window[J ] . Proc Natl Acad Sci U S A, 1999, 96(23): 13496-13500. DOI:10.1073/pnas.96.23.13496.

Ridder D A Schwaninger M NF-kappaB signaling in cerebral ischemia Neuroscience 2009 158 3 995 1006 10.1016/j.neuroscience.2008.07.007 Ridder D A, Schwaninger M. NF-kappaB signaling in cerebral ischemia[J]. Neuroscience, 2009, 158(3): 995-1006. DOI:10.1016/j.neuroscience.2008.07.007.

Fann D Y Lim Y A Cheng Y L Evidence that NF-κB and MAPK Signaling Promotes NLRP Inflammasome Activation in Neurons Following Ischemic Stroke Mol Neurobiol 2017 10.1007/s12035-017-0394-9 Fann D Y, Lim Y A, Cheng Y L, et al . Evidence that NF-κB and MAPK Signaling Promotes NLRP Inflammasome Activation in Neurons Following Ischemic Stroke[J ] . Mol Neurobiol, 2017. [Epub ahead of print ] . DOI:10.1007/s12035-017-0394-9.

张渊张建波唐俊 900MHz电磁辐照对大鼠学习记忆能力和血脑屏障通透性的影响第三军医大学学报 2014 36 3 217 221 http://aammt.tmmu.edu.cn/oa/DArticle.aspx?type=view&id=201308214 张渊, 张建波, 唐俊, 等. 900MHz电磁辐照对大鼠学习记忆能力和血脑屏障通透性的影响[J].第三军医大学学报, 2014, 36(3):217-221. DOI:10.16016/j.1000-5404.2014.03.011.

Zhang Y Zhang J B Tang J Continuous exposure to 900 MHz electromagnetic field alters spatial memory and blood-brain barrier permeability in rats J Third Mil Med Univ 2014 36 3 217 221 http://aammt.tmmu.edu.cn/oa/DArticle.aspx?type=view&id=201308214 Zhang Y, Zhang J B, Tang J, et al .Continuous exposure to 900 MHz electromagnetic field alters spatial memory and blood-brain barrier permeability in rats[J ] .J Third Mil Med Univ, 2014, 36(3):217-221. DOI:10.16016/j.1000-5404.2014.03.011.

Stetler R A Leak R K Gan Y Preconditioning provides neuroprotection in models of CNS disease: paradigms and clinical significance Prog Neurobiol 2014 114 58 83 10.1016/j.pneurobio.2013.11.005 Stetler R A, Leak R K, Gan Y, et al . Preconditioning provides neuroprotection in models of CNS disease: paradigms and clinical significance[J ] . Prog Neurobiol, 2014, 114: 58-83. DOI:10.1016/j.pneurobio.2013.11.005.

Dirnagl U Simon R P Hallenbeck J M Ischemic tolerance and endogenous neuroprotection Trends Neurosci 2003 26 5 248 254 10.1016/S0166-2236(03)00071-7 Dirnagl U, Simon R P, Hallenbeck J M. Ischemic tolerance and endogenous neuroprotection[J]. Trends Neurosci, 2003, 26(5): 248-254. DOI:10.1016/S0166-2236(03)00071-7.

Zemke D Majid A The potential of minocycline for neuroprotection in human neurologic disease Clin Neuropharmacol 2004 27 6 293 298 10.1097/01.wnf.0000150867.98887.3e Zemke D, Majid A. The potential of minocycline for neuroprotection in human neurologic disease[J]. Clin Neuropharmacol, 2004, 27(6): 293-298.

Murray P J Wynn T A Protective and pathogenic functions of macrophage subsets Nat Rev Immunol 2011 11 11 723 737 10.1038/nri3073 Murray P J, Wynn T A. Protective and pathogenic functions of macrophage subsets[J]. Nat Rev Immunol, 2011, 11(11): 723-737. DOI:10.1038/nri3073.

Lee J H Wei Z Z Cao W Regulation of therapeutic hypothermia on inflammatory cytokines, microglia polarization, migration and functional recovery after ischemic stroke in mice Neurobiol Dis 2016 96 248 260 10.1016/j.nbd.2016.09.013 Lee J H, Wei Z Z, Cao W, et al . Regulation of therapeutic hypothermia on inflammatory cytokines, microglia polarization, migration and functional recovery after ischemic stroke in mice[J ] . Neurobiol Dis, 2016, 96: 248-260. DOI:10.1016/j.nbd.2016.09.013.

Hu X Li P Guo Y Microglia/macrophage polarization dynamics reveal novel mechanism of injury expansion after focal cerebral ischemia Stroke 2012 43 11 3063 3070 10.1161/STROKEAHA.112.659656 Hu X, Li P, Guo Y, et al . Microglia/macrophage polarization dynamics reveal novel mechanism of injury expansion after focal cerebral ischemia[J ] . Stroke, 2012, 43(11): 3063-3070. DOI:10.1161/STROKEAHA.112. 659656.

Hayden M S Ghosh S Shared principles in NF-kappaB signaling Cell 2008 132 3 344 362 10.1016/j.cell.2008.01.020 Hayden M S, Ghosh S. Shared principles in NF-kappaB signaling[J]. Cell, 2008, 132(3): 344-362. DOI:10.1016/j.cell.2008.01.020.

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