The Scar as a Barrier to Regeneration

Abstract

Many pioneers in SCI research of the 1950s such as William Windle and Carmine Clemente strongly believed the physical barrier hypothesis early in their careers. Furthermore, they believed the claims of axonal regeneration in adult mammals after administration of pyromen (a bacterial polysaccharide), corticoids, a variety of enzyme treatments, and precise surgery was due to a partial dissolution of the fibroglial scar. The beginning of the demise of the physical barrier hypothesis came from two sources a decade later: (1) the lack of consensus that axonal regeneration was actually enhanced by the above techniques (i.e., a failure of others to repeat these experiments), and (2) the comparative anatomy of spinal cord regeneration, particularly in teleost fish. The classic experiments of Gerald and Mary Bernstein (Bernstein 1978; Bernstein and Bernstein 1967) using goldfish that possess native powers of spinal cord regeneration should be brought to mind. They demonstrated that a dense scar indeed forms at the site of transection of the cord in goldfish. A sleeve of Teflon was inserted into the transection, which prevented axons from crossing this lesion, but did not affect the formation of the scar on either side. Subsequently, the Teflon sheet was removed and the cord was transected once again rostral to the original injury. Spinal cord axons regenerated through the first lesion and of course through the scar that developed there as well. The Bernsteins’ further determined that Teflon deflected axons made synaptic connections without being able to cross the caudal segment of cord, raising the interesting possibility that this synapse formation halted further axonal advance (Bernstein and Bernstein 1971).