One of the biggest challenges humanity faces in venturing off Earth is how to tackle the dangers of cosmic radiation in deep space. When astronauts travel outside the protective ring of our planet's magnetic field, they are subjected to cosmic radiation at levels some studies estimate are up to 1,000 times higher than what we face here on Earth. Researchers have now discovered a novel drug treatment that could not only prevent cognitive deficits caused by this radiation, but actually repair damage in the brain after exposure.

The short- and long-term effects of galactic cosmic rays (GCR) on humans are only just now being fully understood. These particles, generated by high-energy events outside the solar system, are not easily blocked by conventional spacecraft shielding and can cause damage to human tissue. Recent studies have more specifically discovered that exposure to these particles can also result in major neurological damage, euphemistically referred to as "space brain", which is marked by cognitive impairment and diminished judgement.

While crews working on the International Space Station (ISS) are exposed to a degree of GCRs, they are still somewhat protected by the Earth's magnetosphere. Once out of a low-Earth orbit though, astronauts will face exponentially higher levels of this cosmic radiation. Developing a way to combat the long-term effects of these damaging rays is fundamental to any long-term off-Earth mission, including any prospective mission to Mars.

"We are starting to have evidence that exposure to deep space radiation might affect brain function over the long term, but as far as I know, no one had explored any possible countermeasures that might protect astronauts' brains against this level of radiation exposure," says Susanna Rosi, one of the researchers at the University of California, San Francisco (UCSF) who has been investigating this problem for several years.

In a new study the UCSF team investigated whether a drug called PLX5622 could prevent brain damage from doses of radiation comparable to those that astronauts would face in deep space. PLX5622 inhibits a cellular receptor molecule called CSF1R and various similar acting compounds are currently undergoing human clinical trials as cancer treatments. An earlier study from Rosi's team found the drug effectively protected mouse models against cognitive deficits caused by radiation delivered to the brain from cancer treatments.

Here, the team exposed mice to radiation levels similar to what one would face in deep space. After the mice were exposed at the NASA Space Radiation Laboratory in New York, they were transferred back to UCSF and some were treated with PLX5622 for 15 days. In the control group of irradiated animals, cognitive deficits were not seen until three months had passed, indicating a delay in the onset of visible impairments.

The animals treated with PLX5622, on the other hand, didn't display any cognitive defects, performing as well as healthy mice. Examining the animals' brains revealed that while the untreated mice displayed a high volume of activated microglia (the immune cells of the central nervous system), they also exhibited a significant reduction in the number of synapses.

The hypothesis is that the dose of radiation stimulates microglia activity, which can ultimately mediate synaptic elimination resulting in cognitive decline. The drug PLX5622 temporarily depletes the brain of microglia exposed to radiation and prompts their replacement by new, healthy microglia, helping prevent the negative cognitive consequences of radiation from taking hold.

"This is really neat evidence, first that rebooting the brain's microglia can protect cognitive function following radiation exposure, and second that we don't necessarily need to treat immediately following the radiation exposure for the drug to be effective," says Rosi.

The fact that this treatment can be effectively delivered some time after radiation exposure makes this an exciting potential drug for deep space uses. The drug could be administered following an astronaut embarking on a dangerous radiation-heavy space walk, or upon leaving a habitat on Mars that contains some kind of yet-to-be-developed radiation shielding.

The research is also promising for more Earthly outcomes, with the same compounds potentially offering ways to prevent microglia-driven age-related cognitive impairments. Neurodegenerative diseases that stem from inflammation that damages synapses could be targeted by these kinds of microglia-depleting compounds.

The new research was published in the journal Scientific Reports.

Source: University of California, San Francisco

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