A bridge over severed axons

Posted on by under Neuroscience

In research led by Jerry Silver, a professor of neuroscience at Case Western Reserve University, a combination of nerve grafting and treatment with an enzyme was used to regenerate axons in the severed spinal cord of rats, leading to a partial restoration of mobility.

First, short sections of peripheral nerves were removed from sciatic nerve of adult rats with severed spinal cords, and grafted into the area of the spinal injury to form a ‘bridge’ over the damaged sections of the axons. This is not a novel method – grafts of peripheral nerves have been used to successfully regenerate severed peripheral nerves for more than 100 years.

What is new, though, is the enzymatic treatment used to promote re-growth of the axons.

More than 15 years ago, Silver discovered that proteins called chondroitin sulfate proteoglycans, which are synthesized and released at spinal injury sites. These proteins, together with astroglial cells, form a scar around the damaged tissue, which prevents inflammation and cell death. However, proteoglycans also form a mesh-like structure which inhibits axonal regeneration.

Two-and-a-half weeks after the grafts of peripheral nerve had been performed on the rats, Silver and his team used a small pump to deliver chondroitinase, an enzyme isolated from the bacterium Proteus vulgaris, to the injury site. A group of control rats were instead treated with a saline solution.

Upon examination of the rats treated with chondroitinase, it was observed that approximately 20% of nerve fibres sprouting from the bridge formed functional connections in the spinal cord, resulting in markedly improved mobility in those rats. The enzyme promoted axonal regrowth by breaking down the proteoglycans released at the site of injury, so that the mesh which stops the passage of growing axons could not form. In contrast, rats treated with saline showed no signs of axonal regrowth, and there was no improvement in limb movements.

Silver and his team are now aiming to develop the bridge and enzyme method for use in quadriplegics.

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