Breakthrough Nasal Spray Targets Brain Inflammation in Mice

Researchers have created a nasal spray that appears to lessen brain inflammation and potentially restore memory functions in mice. The team from Texas A&M University is optimistic that similar outcomes could be observed in humans, given more time for research and development.

This innovative spray addresses “neuroinflammaging,” which involves chronic stressors affecting the aging brain. It is linked to cognitive decline associated with aging and is believed to contribute to neurological disorders, including Alzheimer’s disease. The scientists liken neuroinflammaging to parts of an engine running too hot over time.

In their experiments, the spray was administered to mice using what are essentially microscopic biological bubbles, known as extracellular vesicles (EVs). These EVs are loaded with proteins and genetic material and are derived from human stem cells.

The mice used in the study were around 18 months old, which is considered older adulthood in mouse studies, comparable to people in their late 50s to late 60s.

The hope is that, as this therapy advances, a simple two-dose nasal spray might eventually replace more invasive and risky treatments or lengthy medication regimens, according to neuroscientist Ashok Shetty.

Interestingly enough, the researchers noted that treatment results were consistent across both male and female mice, reinforcing the universal potential of this approach.

Focusing on microglia, the immune cells in the brain that play a crucial role in memory and learning, the team aimed to reduce neuroinflammation in the hippocampus, a brain region significantly affected by these processes.

Utilizing healthy stem cells—known for their ability to develop into various cell types—is gaining traction in the search for therapeutic solutions. There’s evidence that byproducts of stem cells, like EVs, can do much of the beneficial work while being safer for the body.

The study involved administering two doses of the nasal spray, two weeks apart, to 18-month-old male and female mice. Delivering treatment through the nasal route may allow for more direct access to the brain compared to surgical methods, with the EVs absorbed quickly.

After the treatment, the mice that received the spray performed better than the control group in tests assessing object recognition and spatial memory. Biochemical analyses indicated a decrease in brain inflammation in the treated mice.

These EVs contain microRNAs—tiny genetic regulators that help control how genes express themselves. When released, they can reprogram brain cells, reducing the alert signals that drive neuroinflammaging.

In older mice, this resulted in microglia re-establishing a more typical state, including improved mitochondrial function, which is crucial for energy management in cells.

Neuroscientist Madhu Leelavathi Narayana emphasized that microRNAs serve as master regulators, influencing numerous gene and signaling pathways in the brain. By reducing oxidative stress and reactivating mitochondria, they are essentially reviving neurons.

The implications of this research are significant, particularly as new dementia cases in the US are expected to approach one million annually by 2060—doubling current estimates. This study suggests a potential strategy for lessening age-related neuroinflammation linked to dementia.

Previous animal studies have also indicated that similar EV therapies might aid in recovery from strokes or brain injuries.

While human trials will be essential to validate these findings for conditions like mild cognitive impairment, initial results are certainly promising.

As our understanding of aging continues to evolve, this research aligns well with broader efforts to embrace healthier aging, minimizing the usual biological deterioration that comes with time.

Shetty pointed out that diseases of the brain related to aging, such as dementia, pose serious health challenges globally. The goal is to promote successful brain aging—keeping people engaged and alert, not merely prolonging life but enhancing its quality.

The findings have been detailed in the Journal of Extracellular Vesicles.