Bladder function restored in paralyzed rats

CASE WESTERN RESERVE (US) — Scientists have for the first time restored bladder function in rats with the most severe spinal cord injuries.

The accomplishment paired a traditional nerve bridge graft with a novel combination of scar degrading and growth factor treatments to grow new nerve cells from the thoracic level to the lower spinal cord region.

Although the animals did not regain the ability to walk, the procedure did allow them to recover a strong level of bladder control.

Researchers created the bridge using a scaffold of multiple segments of the animals’ own peripheral nerves. Key to the regeneration was surrounding the graft and both spinal cord stumps with a stimulating growth factor and an enzyme to dissolve scar tissue, which inhibits the nerve fibers from crossing over the bridge and traveling down the spinal cord.

“While urinary control is complex and recovery took several months, it was clear that this primitive function lost to spinal cord injury does possess the capacity to rewire itself, even when a relatively small number of axons are regenerated,” says Jerry Silver,  professor of neurosciences at Case Western Reserve University.

The study is published in the Journal of Neuroscience.

The spinal cord’s role in bladder function is critical, as it relays information between the brain and body. After suffering an spinal cord injury, urinary dysfunction occurs. The loss of control happens because the axons, or nerve fibers that transmit information from neuron to neuron, are disconnected from the brain stem where the body’s urination commands reside.

The creation of the neural bridge, which spans the open cavity between the severed ends of the spinal cord, kills the axons that normally reside within the nerve.

However, the glial cells of the bridge, called Schwann cells, which form an aligned growth promoting pathway, remain alive in the nerve and encourage the severed nearby axons in the spinal cord to enter the bridge and regrow.

Establishing functional regeneration across the gap and down the rats’ spinal cord presented challenges. The first obstacle was coaxing the regenerating axons to enter and transcend the bridge.

Then the axons had to grow well beyond the bridge and form connections capable of relaying nerve signals once they arrived at their destination—approximately 2 centimeters down the spinal cord.

To achieve these results, Silver and Yu-Shang Lee, assistant staff scientist in the Lerner Research Institute of Cleveland Clinic, added Fibroblast Growth Factor to help align the Schwann cells in the graft with the scar tissue cells at the bridge’s interfaces.

Next, they injected an enzyme called chondroitinase to break down inhibitory molecules that often form in scar tissue and curtail regeneration at both ends of the bridge.

“We were especially surprised and excited to discover that once a permissive environment was created, a subset of neurons situated largely within the brainstem, which play important roles in bladder function, slowly re-grew lengthy axons far down the cord,” Silver says.

The model is highly relevant to people with a complete spinal cord injury, a total loss of function below the lesion.

Silver and Lee plan to test the technique in larger animal models before moving to human clinical trials in the US.

Source: Case Western Reserve University