A new strategy to produce sustained growth of central nervous system axons: Continuous mechanical tension

Although a primary strategy to repair spinal cord and other nerve injuries is to bridge the damage with axons, producing axons of sufficient length an d number has posed a significant challenge. Here, we explored the ability o f integrated central nervous system (CNS) axons to grow long distances in r esponse to continuous mechanical tension. Neurons were plated on adjacent m embranes and allowed to integrate, including the growth of axons across a 5 0-mum border between the two membranes. Using a microstepper motor system, we then progressively separated the two membranes further apart from each o ther at the rate of 3.5 mum every 5 min. In the expanding gap, we found thi ck bundles comprised of thousands of axons that responded to this tensile e longation by growing a remarkable 1 cm in length by 10 days of stretch. Thi s is the first evidence that the center portion of synapsed CNS axons can e xhibit sustained "stretch-induced growth." This may represent an important growth mechanism for the elongation of established white matter tracts duri ng development. We also found by doubling the stretch rate to 7 mum/5 min t hat the axon bundles could not maintain growth and disconnected in the cent er of the gap by 3 days of stretch, demonstrating a tolerance limit for the rate of axonal growth. We propose that this newfound stretch-induced growt h ability of integrated CNS axons may be exploited to produce transplant ma terials to bridge extensive nerve damage.