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

The Effect of In Vivo Delivery of Nerve Growth Factor (NGF) Through a Novel T-tube
Chamber on Behavioural Recovery in a Rat Model of Peripheral Nerve Injury
Institution where the work was prepared: University of Calgary, Calgary, AB, Canada
Stephen W.P. Kemp, BSc(Hons), MSc; Aubrey A. Webb; Rajiv Midha; University of Calgary
Various behavioural measurements have traditionally been used to assess recovery following peripheral nerve transection, including the
sciatic functional index (SFI), video gait analysis and ankle rotation measures. However, direct measures that objectively and sensitively
assess the return of sensorimotor function in peripheral nerve injured animals are currently lacking. We sought to assess the extent of
behavioural recovery in both skilled and unskilled sensorimotor tasks, especially locomotion, in normal rats both before and after unilateral
injury to the right sciatic nerve. In addition to traditional methods of sciatic nerve repair, the effect of in vivo delivery of nerve growth
factor (NGF) was evaluated using a novel T-tube chamber nerve conduit. Animals were randomly assigned to one of five treatment
groups: nerve crush (Group 1); direct suture repair (Group 2); transection and T-tube repair with saline administration (Group 3); transection
and T-tube repair with NGF (800 pg/day) administration (Group 4), and; sham-operated controls (Group 5). Locomotor measurements
consisted of (1) ladder rung; (2) tapered beam with crutch; (3) quantitative kinematics, and; (4) ground reaction force determination.
Ground reaction force determination, in particular, provides a sensitive assessment of behavioural recovery by allowing the analysis
of each limb's contribution to vertical (body weight support), fore-aft (braking and propulsion), and mediolateral forces during locomotion.
Sensory testing consisted of two parts: (1) a traditional measure of tactile allodynia was assessed via von Frey filament testing, and;
(2) thermal nociception was evaluated using a modified thermal plantar test. Following serial and final endpoint behavioural measures (3
months), EMG measurements assessed both nerve and muscle conduction velocities. Animals were subsequently sacrificed and final outcome
measures consisted of (1) gastrocnemius muscle weights, and; (2) morphometry (axon/myelination) of EPON embedded section
tissue. Preliminary results indicate that our battery of locomotor tests provide a sensitive, comprehensive, and objective means by which
to evaluate peripheral nerve regeneration. Ongoing evaluation aims to further determine whether animals directly administered NGF
within a T-tube environment show improved sensorimotor behavioural recovery compared to animals administered saline.
Nerve Repair with Introduction of a MEMS-Based Neural Electrode is Not Detrimental to
Muscle Reinnervation
Institution where the work was prepared: University of Michigan, Ann Arbor, MI, USA
Melanie G. Urbanchek, MS, PhD; Antonio P. Peramo, PhD; Daryl R. Kipke, PhD; William M. Kuzon Jr, MD, PhD; Paul S.
Cederna, PhD; University of Michigan
Bioengineers are constructing Micro-Electro-Mechanical Systems (MEMS) that contain integrated sensors, actuators, and electronics on
a common silicon microelectrode substrate. MEMS devices can perform complex functions in small areas such as peripheral nerves.
MEMS could be implanted within a severed peripheral nerve to detect efferent signals for powering prostheses or providing afferent
signals for sensory feedback. This closed-loop neural control of a prosthesis would provide a dramatic increase in functionality for upper
extremity amputees. To achieve this goal, we designed a series of experiments testing the compatibility of MEMS electrodes on axonal
sprouting, regeneration and subsequent muscle reinnervation following neurorrhaphy.
We studied F344 rat peroneal nerve reinnervation of the extensor digitorum longus (EDL) muscle. Our 3 experimental groups received
either no peroneal nerve surgery (Normal), division and repair surgery (Repair), or division and repair with a MEMS electrode introduced
into the distal end of the neurorrhaphy (Repair+Electrode). Each silicon electrode was 10mm X .4mm X 15um with 16 shanks and
embedded inactive wiring. Operated rats recovered for 58-87 days which is early in the postoperative recovery prior to achievement of
maximal reinnervation. EDL maximum tetanic isometric force (Fo) was measured in situ by supramaximal stimulation of the peroneal
nerve proximal to the nerve repair. Peroneal nerve conduction velocity was measured. The EDL muscle was then harvested, weighed,
and the specific force (sFo) was calculated based upon the muscle cross sectional area.
The EDL muscles of the Repair (-43%) and the Repair+Electrode (-33%) groups produced less maximal force when compared with the
Normal group but did not differ from each other. There were no significant differences between the Repair and Repair+Electrode
groups in muscle mass, Fo, sFo, or nerve conduction velocity indicating that the presence of the MEMS probe did not adversely effect
nerve regeneration or muscle reinnervation based upon these outcome measurements.
This study demonstrates that decreased maximal forces early in the reinnervation process discriminate repaired nerve/muscle from normal
for both nerve repair groups. Most importantly the lack of a significant difference between repair groups indicates that intraneural
placement of a MEMS silicon electrode within the peroneal nerve did not adversely effect muscle reinnervation early in recovery.
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