The latest news and information about what's going on with SCI science and research. Brought to you by Sam Maddox, author of the Christopher & Dana Reeve Foundation Paralysis Resource Guide.

More Evidence For Ch'ase

Here’s more just-published evidence that enhancing the area of damage improves chances for recovery after spinal cord injury. The latest work is from the Victor Arvanian lab at the SUNY Stony Brook: “Combination of Chondroitinase ABC and AAV-NT3 promotes neural plasticity at descending spinal pathways following thoracic contusion in rats.”[tp:readmore]

Arvanian, an electrophysiologist, is a former Associate of Lorne Mendell at Stony Brook. Mendell’s lab is one of seven in the Reeve International Research Consortium on Spinal Cord Injury.

The new paper adds to the intrigue of chondroitinase, nicknamed ch'ase. In its natural form, this is a bacteria-formed enzyme that degrades certain kinds of scar tissue that block nerves from growing after SCI. We’ve looked at ch'ase several times; it is the focus of work at the Consortium lab of James Fawcett, and is a primary interest to many other investigators, including Jerry Silver.

Arvanian too has looked at ch'ase before, working on combination treatment strategies with the Fawcett and Mendell labs, as well as several other Consortium members. Here are two recent papers.

This time, the scientists wired up a spinal cord with miniature electrodes – before it was injured. They applied a contusion injury (the most relevant model to human SCI) and recorded in real time what was happening with specific motor nerve axons in the corticospinal and ventrolateral funiculus areas (critical pathways for walking function).

What they found:
We directly demonstrate that after thoracic T10 chronic contusion the disrupted dCST axons spontaneously form new synaptic contacts with individual motoneurons, extending around the contusion cavity, through spared ventrolateral white matter. These detour synaptic connections are very weak and strengthening these connections in order to improve function may be a target for therapeutic interventions following SCI.
 
This is where the ch'ase comes in. To strengthen the weak detours, Arvanian added ch'ase and a growth factor, NT-3, delivered by way of a viral vector.
We found that degradation of scar-related chondroitin sulfate proteoglycans using the enzyme ChondroitinaseABC (ChABC) combined with adeno-associated viral (AAV) vector-mediated prolonged delivery of neurotrophin NT-3 (AAV-NT3) strengthened these spontaneously formed connections in contused spinal cord. Moreover, ChABC/AAV-NT3 treatment induced the appearance of additional detour synaptic pathways innervating dorsomedial interneurons.
 
And after all that, yes, the animals showed improved function:
Improved locomotor function assessed with automated Catwalk highlights the physiological significance of these novel connections.
Posted by Sam Maddox on Jul 31, 2013 2:47 PM America/New_York

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