Researchers Use Nasal Spray To Suppress Brain Inflammation, Reverse ageing

Researchers used a nasal spray containing microRNAs (genetic material) to suppress neuroinflammation and reverse brain ageing, with effects lasting for months. The therapy, developed by the team at Texas A&M University in the US and involving two doses of the spray, also helped restore the brain cells' mitochondria, or power plants, and significantly improved memory in mice. "Brain age-related diseases like dementia are a major health concern worldwide. What we're showing is brain ageing can be reversed, to help people stay mentally sharp, socially engaged and free from age-related decline," Ashok K Shetty, professor and associate director of the Institute for Regenerative Medicine, Texas A&M University, said.

Inflammation "smoulders" deep within the brain's memory centre, creating a persistent brain fog that makes it harder to think, form new memories or even adapt to new environments, all the while increasing the risk of disorders like Alzheimer's disease, the team said.

Described in the Journal of Extracellular Vesicles, the nasal spray therapy suggests that the inflammatory tide responsible for brain ageing and brain fog might be reversible and not involve brain surgery, they said.

The study could also reshape the future of neurodegenerative therapies and may help change how scientists think about brain ageing itself.

The researchers used the body's microscopic delivery vehicles, called 'extracellular vesicles,' which carry genetic cargo termed 'microRNAs'.

"MicroRNAs act like master regulators. They help modulate and regulate many gene and signalling pathways in the brain," author Madhu Leelavathi Narayana, senior research scientist at Texas A&M University's College of Medicine, said.

The nasal spray is packed with extracellular vesicles, which bypass the brain's protective shield and travel directly to the brain tissue, where they are absorbed. Once absorbed into the brain's resident immune cells, the microRNAs suppress systems, such as the NLRP3 inflammasome and the cGAS-STING signalling pathways, known to drive chronic inflammation in ageing brains, the researchers said.

"Intranasal delivery allows us to reach, and treat, the brain directly without invasive procedures," author Maheedhar Kodali, senior research scientist at Texas A&M University's College of Medicine, said. The treatment recharged neuronal mitochondria, or the power plants that live inside the brain's cells – the recharging process cleared the brain fog and physically improved the brain's ability to process and store information.

"We are giving neurons their spark back by reducing oxidative stress and reactivating the brain's mitochondria," Narayana said.

Mice models tested with the nasal spray therapy showed improvements in recognising familiar objects and detecting new objects and changes in their environment.

"We are seeing the brain's own repair systems switch on, healing inflammation and restoring itself," Shetty said. The authors wrote, "The (study) results indicate that IN (intranasal) administration of hiPSC-NSC-EVs (human induced pluripotent stem cell-derived neural stem cells) during late middle age can alter the proinflammatory transcriptome within microglia in the aged brain, leading to reduced oxidative stress and neuroinflammaging, along with improved cognitive and memory function."

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