Scientists revive activity in frozen mouse brains for the first time
‘Cryosleep’ is still the stuff of science fiction, but researchers are getting closer to restoring brain function after deep freezing
A ‘cryosleep pod’ in the 1979 science-fiction film Foreigner.
AJ Pix/20th Century Fox via Alamy
A familiar trope in science fiction is the cryopreserved time traveler, their body deep frozen in suspended animation, then thawed and reawakened with all their mental and physical abilities intact in another decade or century.
Researchers attempting cryogenic freezing and thawing of brain tissue of humans and other animals – mostly young vertebrates – have already shown that neuronal tissue can survive freezing at the cellular level and, after thawing, can function to some degree. But it has not been possible to completely restore the processes essential for proper brain functioning – neuronal firing, cell metabolism and brain plasticity.
A team in Germany has now demonstrated a method of cryopreserving and thawing rat brains that retains some of this functionality. The study, published March 3 Proceedings of the National Academy of SciencesDetails the authors’ use of a method called vitrification, which preserves tissue in a glass-like state, along with a thawing process that preserves living tissue.
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“If brain function is an emergent property of its physical structure, how can we recover it from complete shutdown?” asks Alexander German, a neurologist at the University of Erlangen-Nuremberg in Germany and lead author of the study. He says the findings indicate the potential to one day protect the brain during illness or after severe injury, establish organ banks, and even achieve cryopreservation of whole bodies of mammals.
Mrityunjay Kothari, who studies mechanical engineering at the University of New Hampshire in Durham, agrees that the study advances the state-of-the-art in cryopreservation of brain tissue. He says, “Such advances gradually turn science fiction into scientific possibility.” However, he says applications such as long-term banking of large organs or mammals are well beyond the capabilities of the study.
kept safe for future
The main reason the brain struggles to fully recover from the cold is due to the damage caused by ice crystal formation. These displace or puncture the delicate nanostructures of tissue, thereby disrupting key cellular processes. “Beyond ice, we must pay attention to many things, including osmotic stress and toxicity caused by cryoprotectants,” says German.
German and his colleagues turned to an ice-free method of cryopreservation, called vitrification, in an effort to preserve brain functionality. Vitrification cools liquids so rapidly that the molecules are trapped in a disordered, glass-like state before they have a chance to form ice crystals. “We wanted to see whether function could resume after complete cessation of molecular dynamics in the glass state,” says German.
They first tested their method on 350 micrometer thick slices of mice brains that included the hippocampus – a key brain center for memory and spatial navigation. The brain pieces were pre-treated in a solution containing cryopreservation chemicals before rapid cooling using liquid nitrogen at -196 °C. They were then kept in a freezer at -150 degrees Celsius in a glassy state for ten minutes to seven days.
After thawing the brain pieces in the hot solution, the team analyzed the tissue to see if it retained any functional activity. Microscopy showed that neuronal and synaptic membranes were intact, and tests of mitochondrial activity revealed no metabolic damage. Electrical recordings of neurons showed that, despite moderate deviations compared to control cells, the neurons’ responses to electrical stimuli were close to normal.
Hippocampal neuronal pathways still show synaptic strengthening or ‘long-term potentiation’ that is the basis of learning and memory. However, because such slices naturally deform, observations were limited to a few hours.
The team extended this method to a whole mouse brain, placing it under vitrification at -140 degrees Celsius for eight days. However, frequent changes to the protocol were required to minimize brain shrinkage and toxicity from cryoprotectants.
When the brain was thawed, brain slices were prepared and recordings from the hippocampus confirmed that the neuronal pathways – including hippocampal pathways involved in memory – were alive and could still undergo long-term potentiation. However, because the recordings were made using pieces of brain tissue, the researchers were not able to measure whether the animals’ memories survived cryopreservation.
still science fiction
German and his team are expanding their method from mice to human brain tissue. “We already have preliminary data showing feasibility in human cortical tissue,” he says. The team is also exploring how the vitrification method can be used for whole organ cryopreservation, particularly the heart.
However, Kothari points out that the success rates on the whole-brain protocol were low and the results may not translate directly to larger human organs, which present other challenges. “Some of these challenges relate to heat-transfer barriers and high thermo-mechanical stresses that can cause cracking,” says Kothari.
German says that “better vitrification solutions and cooling and rewarming techniques will be necessary before these principles can be applied to larger human organs.”
This article is reproduced with permission and was first published on 11 March 2026.
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