AAHS ASPN ASRM - 2013 Annual Meeting - American Association ...

The Effect of Cold Storage on Somatosensory Function of Allogenic Nerve Transplants
Institution where the work was prepared: Cleveland Clinic, Cleveland, OH, USA
Michal Molski; Yalcin Kulahci; Ilker Yazici; Maria Siemionow; Cleveland Clinic
INTRODUCTION:
For reconstruction of severe nerve defects in which primary repair of the nerve is impossible, there is a significant need to provide adequate amount of nerve
graft material for the best outcome. Nerve allografts can overcome these difficulties providing unlimited supply and no donor site morbidity, but immunosupression
may be necessary. However when allogenic nerve grafts are preserved by cold storage, they may become less antigenic and more functional.
PURPOSE:
To compare the functional outcome of the cold stored nerve isografts (CSNI) and cold stored nerve allografts (CSNA) following rat sciatic nerve gap repair.
MATHERIAL AND METHODS:
12 Lewis rat recipients were divided into 2 groups of 6 animals each. Nerve grafts were harvested from BN rats (n=6) and Lewis rats (n=6), and stored in UW
solution for 21 days in +4C. A 25mm gap was created in recipient's sciatic nerve and defect was bridged with CSNI in group 1 and CSNA in group 2. Recipients
of allografts received 7 day protocol of ??TCR and CsA. Nonoperated sites served as normal controls. Nerve regeneration was evaluated by pin prick and toe
spread at 3, 6, 12, 24 weeks and by somatosensory evoked potentials examination (SSEP) at 12 and 24 weeks post-transplant. At last observation gastrocnemius
muscle index was achieved. Statistic analysis was performed using Mann-Witnney test.
RESULTS:
At all observations pin prick score in both groups was 3. Average toe spread score in both groups reached the same values at 3, 6, 12, 24 weeks: (0, 1, 2, 2.8)
respectively. SSEP (latencies; % of normal values): at 12 weeks CSNI (17.8, 26.5; 85%, 80%), CSNA (19.9, 28.4; 87%, 80%) at 24 weeks: CSNI (17.6, 24.5;
82%, 87%), CSNA (17.4, 25.7; 82%, 79%). Gastrocnemius muscle weight on the allografted side reached 60% of control side in CSNI group and 42% in CSNA
group.
CONCLUSIONS:
Cold storage of allogenic nerve grafts opens a new horizon in peripheral nerve reconstructive options. Nerve gap repair with allogenic cold stored nerve grafts
(CSNA) followed by short term immunosupression protocol (7 day protocol of ??TCR and CsA) resulted in a good functional outcome comparable to cold stored
nerve isograft (CSNI) transplants.
The Behavioral and Immunological Effect of GM-1 Ganglioside on Nerve Root Regeneration Following C5
Nerve Root Avulsion In a Rat Model
Institution where the work was prepared: Rush University Medical Center, Chicago, IL, USA
Harold Gregory Bach, MD1; Heather Harrison, BS2; Bassem El Hassan, MD3; James M. Kerns, PhD2; Robert M. Leven, PhD2; Mark Gonzalez, MD1; (1)University of Illinois
at Chicago, (2)Rush University Medical Center, (3)Mayo Clinic
Purpose:
This study investigated the effect of GM-1 ganglioside treatment on nerve regeneration following nerve root avulsion in a rat model. This study also assessed
autoimmune responses to GM-1 ganglioside treatment.
Significance:
A brachial plexus injury involves damage to the nerve roots and nerves at or near their exit from the spinal cord. The most devastating lesions are those proximal
to the dorsal root ganglion that can be associated with avulsions of the spinal cord, loss of anterior horn cells and syrinx formation. In many nerve root
avulsions however, the anterior horn cell is preserved and is capable of regenerating motor axons. This makes recovery of motor function possible even in preganglionic
root avulsion injuries. Nerve root avulsion due to traction may occur at birth or from trauma. After brachial plexus injury, enhanced motor sprouting
after nerve root avulsion holds promise to improve outcomes. It is postulated that GM-1 ganglioside stimulates neuronal sprouting and enhances the action
of nerve growth factor. GM-1 ganglioside has been shown to enhance recovery of motor function following spinal cord injury in humans. Immune responses,
marked by the presence of anti-GM-1 antibodies, have been reported following GM-1 ganglioside therapy.
Methodology:
A rat model of C-5 nerve root avulsion causing immediate paralysis of biceps function was created. The Bertelli grooming test asseses return of biceps function.
Sixty-four adult male Sprague-Dawley rats were separated into 4 treatment groups of either C5 nerve root avulsion with or without GM-1 ganglioside
treatment for 30 days or C4-C5 hemilaminectomy with or without GM-1 ganglioside treatment. The Bertelli grooming test assessed functional recovery. To
evaluate for the presence of anti-GM-1 antibodies, serum was collected from 44 rats prior to sacrifice for ELISA testing.
Results:
The Bertelli grooming test revealed no significant functional improvement in the rats treated with GM-1 ganglioside; 44% of GM-1 ganglioside injected rats
attained a good functional outcome compared to 50% for the controls. ELISA testing revealed that the probability of developing an immune reaction by formation
of anti-GM-1 antibodies was 17%. Histological examination found no evidence of neuropathy or inflammation in any of the rats.
Conclusions:
GM-1 ganglioside did not improve biceps function after C-5 nerve root avulsion in a rat model. Immunological testing revealed that 17% of treated rats developed
anti-GM-1 antibodies, which could portend a risk regarding its use. This may explain an increase in the incidence of Guillain-Barre Syndrome in patients
given GM-1 ganglioside.
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