Floor plan - 2013 Annual Meeting - American Association for Hand ...

Increase of Neuronal Camp by Electrical Stimulation or Rolipram Administration and/or
Local Application of Chonodrioitinase ABC Accelerates Motor Axon Outgrowth Across the
Surgical Repair Site of Sectioned Rat Peripheral Nerve
Institution where the work was prepared: University of Alberta, Edmonton, AB, Canada
T. Gordon; M Furey; N Tyreman; E Udina; University of Alberta
Inhibitory proteins associated with myelin and the proteoglycans of the extracellular matrix play a major role in the failure of the central
axons to regenerate after injury. Although also present in the peripheral nervous system (PNS), these molecules do not block PNS
regeneration mainly due to the effective Wallerian degeneration after a nerve lesion. Nevertheless, these molecules could play an
important role in the delay in the onset of axonal regeneration observed after the repair of a transected peripheral nerve. By accelerating
the onset of axonal regeneration the detrimental consequences of long periods of chronic axotomy and Schwann cell denervation
would be diminished and the functional recovery would be improved. In this study we wanted to elucidate the role of cAMP in PNS
regeneration, since its elevation in neurons can overcome inhibition of myelin associated proteins. Electrical stimulation (ES) of the
peripheral nerve accelerates the onset of regeneration and its effect has been linked to increased levels of cAMP in the neuron, therefore
we also wanted to compare the similarities between ES with systemic administration of an agent that increase cellular cAMP levels
in PNS regeneration. We repaired the transected common peroneal (CP) nerve in rats and increased levels of cAMP in the axotomized
neurons with subcutaneous administration of rolipram, a specific inhibitor of the phosphodiesterase, the enzyme that degrades
cAMP. Moreover, we investigated if combination of rolipram treatment with local degradation of the proteoglycans by application of
chondroitinase ABC (cABC) in the distal stump, would elicit an additive enhancement in nerve regeneration. Rolipram treatment significantly
increased the mean (± SE) number of motor (but not sensory) neurons that regenerated their axons across the repair site at 1w
and 2w with 194±14 of a total of 336±19 CP motoneurons regenerating their axons a 10mm distance into the distal nerve stump at 2w
as compared to 109±20 motoneurons that regenerated their axons after saline treatment. This effect mimicked the effect of 1h of ES
(at 20Hz) applied to the proximal stump of the transected and repaired femoral nerve in accelerating axon outgrowth. Both rolipram
and ES significantly increased the number of motor axons crossing the lesion site at earlier time points by ~3-fold when compared to
the control groups. Local application of cABC also accelerated axonal outgrowth but the effect was not additive when combined with
rolipram. We conclude that pharmacological elevation of cAMP accelerates PNS axonal outgrowth similar to ES.
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