Intranasal Delivery of Brain-Derived Neurotrophic Factor (BDNF)-Loaded Small Extracellular Vesicles for Treating Acute Spinal Cord Injury in Rats and Monkeys

Journal of Extracellular Vesicles, 2025 · DOI: https://doi.org/10.1002/jev2.70066 · Published: January 1, 2025

Simple Explanation

This study explores a new way to treat spinal cord injuries using tiny particles called small extracellular vesicles (sEVs). These sEVs are loaded with a protein called brain-derived neurotrophic factor (BDNF), which helps nerve cells grow and survive. The researchers delivered these BDNF-sEVs into the nose of rats and monkeys with spinal cord injuries. They found that this treatment helped the animals recover some movement and reduced inflammation in their spinal cords. This method of delivering BDNF using sEVs through the nose could be a promising new way to treat spinal cord injuries in people because it can bypass the blood-brain barrier and directly target the injured area.

Study Duration

56 Days (Rats), 7 Months (Monkeys)

Participants

Rats (Sprague-Dawley, female, 250 ± 25 g), Monkeys (cynomolgus, male, 3–4 years old, 4–5 kg)

Evidence Level

Level II: Experimental study in animal models (rats and monkeys)

Key Findings

1
BDNF loading enhances the neurite outgrowth promoted by sEVs in cultured neurons, suggesting an improved neurotrophic effect.
2
Intranasal administration of BDNF-sEVs reduces glial responses and pro-inflammatory cytokine production in acute SCI rats and monkeys, indicating an anti-inflammatory effect.
3
BDNF-sEV treatment improved neural repair and functional recovery compared to sEV treatment alone in both rat and monkey SCI models.

Research Summary

The study investigates the therapeutic potential of intranasally administered BDNF-loaded small extracellular vesicles (BDNF-sEVs) for acute spinal cord injury (SCI) in rats and monkeys. Results demonstrate that BDNF-sEVs promote neurite outgrowth in vitro, reduce glial responses and inflammation in vivo, enhance neuronal survival and angiogenesis, and improve functional performance in SCI animal models. The findings suggest that intranasal administration of BDNF-sEVs could be a promising therapeutic strategy for clinical treatment of acute SCI by combining the benefits of both sEVs and BDNF.

Practical Implications

Clinical Translation Potential

Intranasal delivery of BDNF-sEVs presents a non-invasive method for delivering neuroprotective and regenerative factors to the injured spinal cord, potentially improving outcomes for acute SCI patients.

Combination Therapy Approach

The study supports the use of combination therapies, leveraging the benefits of both sEVs and BDNF to address multiple aspects of SCI pathology, including inflammation, neuronal survival, and axonal regeneration.

Drug Delivery System

sEVs serve as an effective drug delivery system for BDNF, overcoming the limitations of direct BDNF administration due to its poor BBB penetration and rapid degradation.

Study Limitations

1
The study relies on animal models, and further research is needed to confirm the efficacy and safety of BDNF-sEVs in human clinical trials.
2
The long-term effects of BDNF-sEV treatment on SCI recovery and potential side effects require further investigation.
3
The optimal dosage and administration schedule of BDNF-sEVs for SCI treatment need to be determined.

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