Internal Cooling System Improves Recovery After Brain Injury in Mice

Cooling down a damaged brain can protect neurons by suppressing inflammation.¹ But lowering the body temperature externally comes with a host of complications and can lead to impaired clotting and cardiac arrhythmias.

Now, researchers led by Takeshi Sakurai at the University of Tsukuba have found a way to leverage hypothermia without causing adverse effects. In a study published in The Journal of Neuroscience, Sakurai and his team showed that cooling the brain from within by activating a specific population of hibernation neurons can protect the brains of mice from the worst effects of traumatic brain injury.²

For their study, Sakurai and his team focused on a population of neurons in the mouse hypothalamus called Q neurons that can induce a state of hypothermia without the need for cooling blankets or cold caps.³ In 2020, scientists from another research group found that the hypothermia these neurons induce is reversible and resembles hibernation.

However, researchers had not previously explored whether Q neuron-induced hypothermia (QIH) had the same therapeutic benefits as external hypothermia. To test this, Sakurai and his team activated Q neurons using a genetic technology that modulates cellular activity in mouse models of brain injury. This kept them in a state of hypothermia for 24 hours after their injury.

Next, the team compared the animals’ post-injury recovery to that of control animals. Mice that experienced hypothermia showed progressive recovery in their motor abilities and outperformed control mice by 10 days after injury. The QIH-exposed mice also showed improved grip strength and coordination, and they exhibited less anxious behavior than their untreated counterparts.

Encouraged by the behavioral findings, the researchers turned to cellular analyses. Neurons sustained less damage in the hypothermia group as seen by higher levels of the mature neuron marker NeuN. The brains of treated animals showed fewer signs of inflammation.

While Q neurons have yet to be identified in humans, the authors hope that the study shows a route to safer hypothermia therapies in other species. “Optimizing the timing and duration of this treatment after injury, testing across additional injury models, and evaluating safety and efficacy in larger animals will be important next steps,” said Sakurai in a press release.