Delivery of an adenoviral vector to the crushed recurrent laryngeal nerve.
OBJECTIVE
Objectives were to create a model of recurrent laryngeal nerve injury for testing the efficacy of potential therapeutic viral gene therapy vectors and to demonstrate that remote injection of a viral vector does not cause significant additional neuronal injury.


METHODS
Animal model.


METHODS
Rats were randomly assigned to three groups of 10 animals each. In group I, the recurrent laryngeal nerve was crushed. In group II, the nerve was crushed and then injected with an adenoviral vector containing no transgene. In group III, the nerve was identified but was not crushed. Rats were killed at 1 week, and their larynges and brainstems were cryosectioned in 15-microm sections. Laryngeal cryosections were processed for acetylcholine histochemical analysis (motor endplates) followed by neurofilament immunoperoxidase (nerve fibers). Percentage of nerve-endplate contact was determined and compared between groups. Fluorescent in situ hybridization was performed on brainstem sections from rats in group II to confirm the presence of virus.


RESULTS
No significant difference in percentage of nerve-endplate contact exists between the two crushed-nerve groups (groups I and II) (P =.88). The difference between both crushed-nerve groups and the group with noncrushed nerves (group III) was highly significant (P <.0001). The presence of virus was confirmed in group II rats.


CONCLUSIONS
Crush provides a significant measurable injury to the recurrent laryngeal nerve and may be used as a model to explore therapeutic interventions for nerve injury. The remote injection of viral vector did not cause significant additional neuronal injury. Remote delivery of viral vectors to the central nervous system holds promise in the treatment of recurrent laryngeal nerve injury and central nervous system diseases.
Rubin
Adam
A
Department of Otorhinolaryngology, University of Michigan, Ann Arbor, USA.
Mobley
Bret
B
Hogikyan
Norman
N
Bell
Kimberly
K
Sullivan
Kelli
K
Boulis
Nicholas
N
Feldman
Eva
E
D000256:Adenoviridae / Q000235:genetics* / Q000302:isolation & purification; D000818:Animals; D001370:Axonal Transport / Q000502:physiology; D001933:Brain Stem / Q000473:pathology; D004195:Disease Models, Animal; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors; D007124:Immunoenzyme Techniques; D009045:Motor Endplate / Q000473:pathology; D009409:Nerve Crush / Q000379:methods*; D009412:Nerve Fibers / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012009:Recurrent Laryngeal Nerve / Q000473:pathology; D061226:Recurrent Laryngeal Nerve Injuries; D014826:Vocal Cord Paralysis / Q000473:pathology / Q000628:therapy*