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Minocycline attenuates microglial response and reduces neuronal death after cardiac arrest and cardiopulmonary resuscitation in mice

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Summary

The possible role of minocycline in microglial activation and neuronal death after cardiac arrest (CA) and cardiopulmonary resuscitation (CPR) in mice was investigated in this study. The mice were given potassium chloride to stop the heart beating for 8 min to achieve CA, and they were subsequently resuscitated with epinephrine and chest compressions. Forty adult C57BL/6 male mice were divided into 4 groups (n=10 each): sham-operated group, CA/CPR group, CA/CPR+minocycline group, and CA/CPR+vehicle group. Animals in the latter two groups were intraperitoneally injected with minocycline (50 mg/kg) or vehicle (normal saline) 30 min after recovery of spontaneous circulation (ROSC). Twenty-four h after CA/CPR, the brains were removed for histological evaluation of the hippocampus. Microglial activation was evaluated by detecting the expression of ionized calcium-binding adapter molecule-1 (Iba1) by immunohistochemistry. Neuronal death was analyzed by hematoxylin and eosin (H&E) staining and the levels of tumor necrosis factor-alpha (TNF-α) in the hippocampus were measured by enzyme-linked immunosorbent assay (ELISA). The results showed that the neuronal death was aggravated, most microglia were activated and TNF-α levels were enhanced in the hippocampus CA1 region of mice subjected to CA/CPR as compared with those in the sham-operated group (P<0.05). Administration with minocycline 30 min after ROSC could significantly decrease the microglial response, TNF-α levels and neuronal death (P<0.05). It was concluded that early administration with minocycline has a strong therapeutic potential for CA/CPR-induced brain injury.

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Authors and Affiliations

  1. Department of Anesthesiology, Institute of Anesthesia and Critical Care, Huazhong University of Science and Technology, Wuhan, 430022, China

    Qian-yan Wang  (王黔艳), Qing Zhang  (张 清) & Shang-long Yao  (姚尚龙)

  2. Department of Emergency, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China

    Peng Sun  (孙 鹏)

Authors
  1. Qian-yan Wang  (王黔艳)
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  2. Peng Sun  (孙 鹏)
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  3. Qing Zhang  (张 清)
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  4. Shang-long Yao  (姚尚龙)
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Corresponding authors

Correspondence to Qing Zhang  (张 清) or Shang-long Yao  (姚尚龙).

Additional information

This project was supported by grants from the National Natural Science Foundation of China (No. 81201444 and No. 81101401).

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Wang, Qy., Sun, P., Zhang, Q. et al. Minocycline attenuates microglial response and reduces neuronal death after cardiac arrest and cardiopulmonary resuscitation in mice. J. Huazhong Univ. Sci. Technol. [Med. Sci.] 35, 225–229 (2015). https://doi.org/10.1007/s11596-015-1415-4

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  • DOI: https://doi.org/10.1007/s11596-015-1415-4

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