Journal of Anesthesia

, Volume 30, Issue 3, pp 427–436 | Cite as

Isoflurane postconditioning induces concentration- and timing-dependent neuroprotection partly mediated by the GluR2 AMPA receptor in neonatal rats after brain hypoxia–ischemia

  • Ying Xu
  • Hang Xue
  • Ping ZhaoEmail author
  • Yating Yang
  • Guoyu Ji
  • Weiwei Yu
  • Guang Han
  • Mengmeng Ding
  • Feifei Wang
Original Article



It has been demonstrated that preconditioning with 1.5 % isoflurane reduces hypoxia/ischemia (HI)-induced brain loss/injury in neonatal rats. Ca2+ influx mediated by α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptors (AMPARs) is involved in HI-induced neuronal death. Here, we investigated the effective concentrations and time windows for neuroprotection by isoflurane postconditioning in neonatal rats after brain HI and determined whether GluR2-containing AMPARs mediate this neuroprotection.


Seven-day-old Sprague–Dawley (SD) rats were randomly divided into eight groups (n = 40 in each). The rats underwent left common carotid arterial ligation (brain HI) or sham surgery, followed by exposure to 8 % oxygen for 2 h at 37 °C in a thermoregulated environment. Post-conditioning with 1, 1.5, or 2 % isoflurane for 30 min was performed immediately after brain HI. Others were post-treated with 1.5 % isoflurane for 30 min at 3, 6, and 12 h after brain HI. The weight ratio, neuronal density ratio in the ventral posteromedial thalamic nucleus, and retrosplenial granular cortex of left to right cerebral hemispheres at 7 days after brain HI were evaluated in all groups. Cerebral hemispheres were harvested for Western-blot analysis of GluR2 on the cellular membranes 24 h after HI or sham surgery in neonatal rats from the sham group, the HI group, and the HI + immediate exposure to the 1.5 % isoflurane group. In another experiment, the function of learning and memory were assessed in adolescence (4 weeks) using Morris water maze.


Compared with the control (sham) group, brain HI decreased the weight ratio and the neuronal density ratio in the ventral posteromedial thalamic nucleus and the retrosplenial granular cortex of the left to right cerebral hemispheres (p < 0.05). These effects of brain HI were reduced by postconditioning with 1.5 or 2 % isoflurane for 30 min within 6 h of HI, which coincided with the results of Morris water maze. GluR2 protein expression on cellular membranes was reduced after HI compared with sham surgery group (p < 0.05); this down-regulation was attenuated by isoflurane postconditioning.


Postconditioning with 1.5 and 2 % isoflurane affords neuroprotection in neonatal rats. The time window for isoflurane postconditioning to be effective against neonatal HI-induced brain injury was 0–6 h after HI. This protection may be mediated by GluR2-containing AMPARs.


Isoflurane Postconditioning Hypoxia Ischemia Neonatal GluR2 AMPAR 



This study was supported by a grant (No. 81178782; to Ping Zhao) from the National Natural Science Foundation of China.

Compliance with ethical standards

All feasible efforts were made to minimize animal suffering, to reduce the number of animals used, and to utilize alternatives to in vivo techniques.

Conflict of interest

The author(s) declare that they have no competing interests.


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Copyright information

© Japanese Society of Anesthesiologists 2016

Authors and Affiliations

  • Ying Xu
    • 1
  • Hang Xue
    • 1
  • Ping Zhao
    • 1
    Email author
  • Yating Yang
    • 1
  • Guoyu Ji
    • 1
  • Weiwei Yu
    • 1
  • Guang Han
    • 1
  • Mengmeng Ding
    • 1
  • Feifei Wang
    • 1
  1. 1.Department of AnesthesiologyShengjing Hospital, China Medical UniversityShenyangChina

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