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Hypothermia evoked by stimulation of medial preoptic nucleus protects the brain in a mouse model of ischaemia

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  • Shuai Zhang

    (Southern University of Science and Technology)

  • Xinpei Zhang

    (Southern University of Science and Technology)

  • Haolin Zhong

    (Southern University of Science and Technology)

  • Xuanyi Li

    (Southern University of Science and Technology)

  • Yujie Wu

    (Southern University of Science and Technology)

  • Jun Ju

    (Southern University of Science and Technology)

  • Bo Liu

    (Southern University of Science and Technology)

  • Zhenyu Zhang

    (Southern University of Science and Technology)

  • Hai Yan

    (Southern University of Science and Technology)

  • Yizheng Wang

    (Fudan University)

  • Kun Song

    (Southern University of Science and Technology)

  • Sheng-Tao Hou

    (Southern University of Science and Technology)

Abstract

Therapeutic hypothermia at 32-34 °C during or after cerebral ischaemia is neuroprotective. However, peripheral cold sensor-triggered hypothermia is ineffective and evokes vigorous counteractive shivering thermogenesis and complications that are difficult to tolerate in awake patients. Here, we show in mice that deep brain stimulation (DBS) of warm-sensitive neurones (WSNs) in the medial preoptic nucleus (MPN) produces tolerable hypothermia. In contrast to surface cooling-evoked hypothermia, DBS mice exhibit a torpor-like state without counteractive shivering. Like hypothermia evoked by chemogenetic activation of WSNs, DBS in free-moving mice elicits a rapid lowering of the core body temperature to 32-34 °C, which confers significant brain protection and motor function reservation. Mechanistically, activation of WSNs contributes to DBS-evoked hypothermia. Inhibition of WSNs prevents DBS-evoked hypothermia. Maintaining the core body temperature at normothermia during DBS abolishes DBS-mediated brain protection. Thus, the MPN is a DBS target to evoke tolerable therapeutic hypothermia for stroke treatment.

Suggested Citation

  • Shuai Zhang & Xinpei Zhang & Haolin Zhong & Xuanyi Li & Yujie Wu & Jun Ju & Bo Liu & Zhenyu Zhang & Hai Yan & Yizheng Wang & Kun Song & Sheng-Tao Hou, 2022. "Hypothermia evoked by stimulation of medial preoptic nucleus protects the brain in a mouse model of ischaemia," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
  • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-34735-2
    DOI: 10.1038/s41467-022-34735-2
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