What is the significance of using MSCs in brain injury?

MSCs have the ability to secrete neurotrophic factors that aid in neuronal repair and regeneration.

How does intranasal delivery enhance MSC treatment?

Intranasal delivery allows for direct access to the central nervous system, improving MSC absorption and migration to the injury site.

What role do proteolytic enzymes play in this study?

Proteolytic enzymes degrade the extracellular matrix, enhancing the permeability of nasal epithelial cells for better MSC absorption.

What were the main findings of the study?

The study found that intranasal MSC delivery effectively directed cells to the injury site and promoted remyelination through neurotrophic factor secretion.

Can this method be applied to other types of injuries?

While this study focuses on traumatic brain injury, the intranasal delivery method may have potential applications in other neurological conditions.

What are the next steps for this research?

Future research may explore the long-term effects of MSC treatment and the potential for clinical applications in human patients.

Intranasal Mesenchymal Stem Cell Delivery in a Mouse Model of Traumatic Brain Injury

JoVE Encyclopedia of Experiments

Neuroscience

0 views • 2:39 min • June 17th, 2025

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Begin with an anesthetized mouse with a traumatic brain injury.

At the injury site, axonal demyelination and neuronal damage trigger the release of pro-inflammatory cytokines.

Secure the mouse and intranasally deliver a proteolytic enzyme.

Next, position the mouse face up for a short duration and repeat the enzyme delivery.

The proteolytic enzymes degrade the extracellular matrix in the nasal epithelia and enhance the cell permeability.

Then, intranasally administer the labeled mesenchymal stem cell, or MSC solution.

Hold the mouse’s head upright for a while to prevent premature drainage and allow MSC absorption into the nasal tissue.

Repeat the MSC delivery process.

Allow the mouse to recover.

The chemotactic signals of pro-inflammatory cytokines direct MSCs to migrate from the nasal cavity to the brain injury site.

At the injury site, MSCs secrete neurotrophic factors that promote remyelination. This highlights MSCs’ neurotherapeutic potential for neuronal repair.

For cell delivery, after confirming a lack of response to toe pinch, scruff the mouse while immobilizing the skull. Place the tip of a pipette containing 4 units of hyaluronidase per microliter of PBS near the nare of the mouse at a 45-degree angle and administer 3 microliters of hyaluronidase suspension into each nostril. Place the animal face up on a clean pad for five minutes before repeating the treatment four times for a total of 100 units of hyaluronidase treatment.

After the last treatment, place the mouse back onto the pad for 30 minutes before restraining the mouse, as just demonstrated. With the head immobilized, administer 3 microliters of the mesenchymal stem cell suspension into each nostril over a period of three seconds per solution delivery, holding the mouse in position for 30 seconds until the sample drops have completely disappeared. After two minutes, repeat the delivery up to three times until the entire volume of mesenchymal stem cell has been delivered. Then return the mouse to its cage with monitoring until full recumbency.