A combo of peripheral nerve grafts, aFGF, and Chondroitinase ABC chronic recovery

This poster by Mark DePaul and Jerry Silver of Case Western Reserve along Yu-Shang Lee of Cleveland Clinic received honors at the Asilomar Regeneration Conference at Pacific Grove California in addition to being at the Society of Neuroscience 2013.

Program#/Poster#: 168.01/PP8

Title: A combination of peripheral nerve grafts, aFGF, and Chondroitinase ABC promotes regeneration and improvements in bladder function after chronic contusive thoracic spinal cord injury in adult rats

Authors: M. DEPAUL1, C.-Y. LIN2, K. PARK2, J. SILVER1, *Y.-S. LEE2;
1Neurosciences, Case Western Reserve Univ., Cleveland, OH; 2Neurosci, Cleveland Clinic.,
CLEVELAND, OH

Abstract: The purpose of this study was to determine whether peripheral nerve grafts (PNG) + acidic fibroblast growth factor (aFGF) + chondroitinase ABC (ChABC) can promote axonal regeneration through a severe T8 chronic contusive lesion cavity in the spinal cord and whether such regeneration can improve bladder control. .Adult rats were divided into 3 groups: (1) Sham control (laminectomy only), (2) T8 contusive SCI only, and (3) T8 contusive SCI+PNG+aFGF+ChABC. The observation period was 10 months after the original SCI.
In group 3 animals, the PNG+aFGF+ChABC treatment was delayed for two months after the original SCI. We tested bladder function by the use of metabolic cages (twice per month after injury or treatment) and urodynamic measurements with EUS EMG recordings at the end of the study. Our analyses revealed a significantly higher frequency of urination (closer to that in sham animals) in the PNG+aFGF+ChABC treated group than in the contusive injury only animals 10 months after SCI.
In addition, urodynamic studies showed that PNG+aFGF+ChABC treated animals had a reduction in residual urine volume in comparison to the contusive injury only animals. In terms of bladder morphology, the triple combination animals had significantly lower bladder weights (more like that of sham animals) than the contusive injury animals. Our anatomical analyses revealed a surprising amount of regeneration of certain brainstem fiber systems in the triple combination animals. Two descending fiber populations including the 5-HT and TH systems, could re-grow robustly into the PNG and exit the PNG into the distal end of the spinal cord. These two nerve fiber systems are important for bladder control. There were no improvements in locomotion in the bridged animals. These data suggest that certain types of chronically injured axons still have the capacity to regrow long distances within a permissive environment but also in the distal cord beyond the graft and bring about a measure of functional recovery.

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