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

• Published in: Nature communications Vol. 13; no. 1; p. 6890
• Main Authors: Zhang, Shuai, Zhang, Xinpei, Zhong, Haolin, Li, Xuanyi, Wu, Yujie, Ju, Jun, Liu, Bo, Zhang, Zhenyu, Yan, Hai, Wang, Yizheng, Song, Kun, Hou, Sheng-Tao
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 12.11.2022; Nature Publishing Group; Nature Portfolio
• Subjects: 631/1647/334/1874/345; 631/378/1689/534; 64; 64/60; 692/617/375/1370/534; 692/699/375/1370/534; 9/25; 96/10; 96/34; 96/35; 96/63; Animals; Body temperature; Brain; Complications; Deep brain stimulation; Disease Models, Animal; Hibernation; Humanities and Social Sciences; Hypothermia; Ischemia; Mice; multidisciplinary; Neuroprotection; Preoptic area; Preoptic area (medial); Preoptic Area - physiology; Science; Science (multidisciplinary); Shivering; Shivering - physiology; Stimulation; Stroke; Surface cooling; Thermogenesis; Torpor
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-022-34735-2

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. Developing brain-protective hypothermia is a medical challenge. Here, the authors show that deep brain stimulation of a particular brain area is a new way to trigger the body into a hibernation-like state with reduced body temperature and brain protection in a mouse model of stroke.