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Intranasal Human NSC‐Derived EVs Therapy Can Restrain Inflammatory Microglial Transcriptome, and NLRP3 and cGAS‐STING Signalling, in Aged Hippocampus

Tiny “fires” of inflammation smolder deep within the brain’s memory center, 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 to disorders like Alzheimer’s disease.

Scientists call this slow burn “neuroinflammaging,” and for decades it was thought to be the inevitable price of growing older.

Until now.

A landmark study from researchers at the Texas A&M University Naresh K. Vashisht College of Medicine suggests the inflammatory tide responsible for brain aging and brain fog might actually be reversible. And the solution doesn’t involve brain surgery, but a simple nasal spray.

Led by Dr. Ashok Shetty, university distinguished professor and associate director of the Institute for Regenerative Medicine, along with senior research scientists Dr. Madhu Leelavathi Narayana and Dr. Maheedhar Kodali, the team developed a nasal spray that, with just two doses, dramatically reduced brain inflammation, restored the brain’s cellular power plants and significantly improved memory.

The most surprising part? It all happened within weeks and lasted for months.

The findings, published in the Journal of Extracellular Vesicles, could reshape the future of neurodegenerative therapies and may even change how scientists think about brain aging itself.

Abstract: Intranasal Human NSC-Derived EVs Therapy Can Restrain Inflammatory Microglial Transcriptome, and NLRP3 and cGAS-STING Signalling, in Aged Hippocampus.


Neuroinflammaging, a moderate, chronic, and sterile inflammation in the hippocampus, contributes to age-related cognitive decline. Neuroinflammaging comprises the activation of the nucleotide-binding domain, leucine-rich repeat family, and pyrin domain-containing 3 (NLRP3) inflammasomes, and the cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) pathway that triggers type 1 interferon (IFN-1) signalling. Studies have shown that extracellular vesicles from human induced pluripotent stem cell-derived neural stem cells (hiPSC-NSC-EVs) contain therapeutic miRNAs that can alleviate neuroinflammation. Therefore, this study examined the effects of late middle-aged (18-month-old) male and female C57BL6/J mice receiving two intranasal doses of hiPSC-NSC-EVs on neuroinflammaging in the hippocampus at 20.5 months of age.

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