Hibernation-like hypothermia suppresses neuroinflammation and promotes functional recovery after brain injury

Tsukuba, Japan—Traumatic brain injury (TBI), commonly caused by incidents such as vehicular accidents or falls, initiates a cascade of inflammatory responses following the primary mechanical insult. This secondary inflammatory reaction exacerbates neuronal damage and often results in persistent motor and cognitive impairments. Although therapeutic hypothermia—lowering core body temperature to limit neural injury—has attracted considerable clinical interest, conventional methods involving external cooling remain physiologically taxing and are constrained in their practical application.

To overcome these limitations, researchers at University of Tsukuba previously developed a technique to induce a deep hypothermic state, termed QIH (Q neuron-induced hypothermic/hypometabolic state), through targeted chemical stimulation of hypothalamic Q neurons. In the current study, QIH was applied to a murine model of mild TBI, leading to sustained reductions in core body temperature. This hibernation-like hypothermic state significantly attenuated the hyperactivation of inflammation-associated glial cells, thereby preserving neuronal integrity and accelerating motor function recovery.

These findings suggest that harnessing the brain's intrinsic thermoregulatory mechanisms to induce hypothermia may provide a safer, more physiologically compatible, and clinically viable therapeutic strategy for traumatic and other neurologically induced brain injuries.

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This study was supported by the World Premier International Research Center Initiative (WPI), JSPS KAKENHI Grant-in-Aid for Scientific Research (S) [21H05036 to T.S.], Grant-in-Aid for Challenging Research (Exploratory) [21K19287 to T.S.], and Grant-in-Aid for Transformative Research Areas (A) [23H04941 to T.S.]; by the JSPS Fund for the Promotion of Joint International Research [22K21351 to T.S.]; by JST SPRING [JPMJSP2124 to R.Y.]; by JST CREST [JPMJCR24T4 to T.S.]; and by the AMED Research Program [JP21zf0127005 to T.S.]. Additional support was provided by the Canon Foundation and the Mitsubishi Foundation (both to T.S.).

_{Original Paper}

Title of original paper:
Q Neuron-Induced Hypothermia Promotes Functional Recovery and Suppresses Neuroinflammation After Brain Injury

Journal:
Journal of Neuroscience

DOI:
10.1523/JNEUROSCI.1035-25.2025

_{Correspondence}

Professor SAKURAI, Takeshi
Institute of Medicine / International Institute for Integrative Sleep Medicine (WPI-IIIS), Tsukuba Institute for Advanced Research (TIAR), University of Tsukuba

_{Related Link}

Tsukuba Institute for Advanced Research (TIAR)

International Institute for Integrative Sleep Medicine (WPI-IIIS)

Institute of Medicine

About the World Premier International Research Center Initiative (WPI)
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About International Institute for Integrative Sleep Medicine (IIIS), University of Tsukuba
World-class institute for sleep medicine, aiming to solve the mechanism of sleep/wakefulness by conducting basic to translational research
The mission of IIIS is to be a multidisciplinary, international hub for the research to elucidate the function of sleep and the fundamental mechanisms of sleep/wake regulation, to elucidate molecular pathogenesis of sleep disorders and related diseases, to develop preventive measures, diagnostic methods, and treatments for sleep.