Hypothermia evoked by stimulation of medial preoptic nucleus protects the brain in a mouse model of ischaemia.
Shuai ZhangXinpei ZhangHaolin ZhongXuanyi LiYujie WuJun JuBo LiuZhenyu ZhangHai YanYizheng WangKun SongSheng-Tao HouPublished in: Nature communications (2022)
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.
Keyphrases
- deep brain stimulation
- cardiac arrest
- parkinson disease
- brain injury
- obsessive compulsive disorder
- cerebral ischemia
- subarachnoid hemorrhage
- mouse model
- resting state
- white matter
- physical activity
- risk factors
- chronic kidney disease
- adipose tissue
- high fat diet induced
- type diabetes
- magnetic resonance
- newly diagnosed
- end stage renal disease
- metabolic syndrome
- ejection fraction
- computed tomography
- atrial fibrillation
- functional connectivity
- blood brain barrier
- contrast enhanced
- patient reported outcomes
- patient reported