No abstract

We demonstrate that a conduit filled with platelet-rich fibrin can induce limited, but appropriate, sensory and motor recovery across a 12-cm nerve gap repaired 3.25 years post trauma, without sacrificing a sensory nerve, can reduce existing excruciating neuropathic pain to tolerable, and allow avoidance of an indicated upper-extremity amputation. We believe the technique can be improved to induce more extensive and reliable neurological recovery.

Isolated adult human dorsal root ganglion neurons survive in culture for more than 2 1/2 months, extend processes, and remain electrically excitable, without exogenous neurotrophins. These results suggest that, adult human sensory neurons do not require exogenous neurotrophins for survival and process outgrowth, or that sufficient factors were provided by the small number of satellite cells in the cultures. In addition, the neurons survive well in spite of an initial period of up to 14 hours of hypoxia, between the time the aorta was clamped and when the plated neurons were placed in an incubator with the appropriate O2/CO2 environment.

Sensory axons do not regenerate into or within the spinal cord because of the presence of the axon regeneration inhibitor chondroitin sulfate proteoglycan (CSPG) on activated astrocytes. In the peripheral nervous system, CSPG associated with denervated Schwann cells retards axon regeneration, but regeneration occurs because the balance of regenerating, inhibiting, and promoting factors favors regeneration. The present experiments were aimed at determining the mechanism by which Schwann cells inhibit adult human dorsal root ganglia (H-DRG) neuron growth cone elongation and substrate specificity, restricting the growth cones to Schwann cell membranes and inhibiting their growth onto a poly-l-lysine/laminin substrate. Neurites of H-DRG neurons free of soma contact with Schwann cells, or after the Schwann cell membranes' CSPG had been digested, were 11.1-fold longer than those of neurons in soma contact with untreated Schwann cells. Growth cones of DRG neuron somas without Schwann cell CSPG showed no outgrowth inhibition or substrate specificity. These results indicate that the Schwann cell CSPG influences act via contact with neuron somas but not growth cones. These results suggest that eliminating CSPG associated with Schwann cells within DRG in vivo will make the neurons' growth cones insensitive to the regeneration inhibitory influences of CSPG, allowing them to regenerate through the dorsal root entry zone and into and within the spinal cord, where they can establish appropriate and functional synaptic connections.