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

Shuai Zhang, Xinpei Zhang, Haolin Zhong, Xuanyi Li, Yujie Wu, Jun Ju, Bo Liu, Zhenyu Zhang, Hai Yan, Yizheng Wang, Kun Song () and Sheng-Tao Hou ()
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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

Nature Communications, 2022, vol. 13, issue 1, 1-15

Abstract: 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.

Date: 2022
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DOI: 10.1038/s41467-022-34735-2

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