Motor nerve injuries are often devastating;even the most sophisticated repair of an injured nerve rarely leads to satisfactory restoration of function. Damage to the facial nerve is particularly disabling because the ability to blink, eat, speak, and communicate through facial expressions are all dramatically affected. The associated severe facial disfigurement also has profound social and psychological consequences. Over the past five years, our laboratory has created a highly quantitative methodology for real-time measurement of recovery from facial nerve injury in the rodent. With this system we have demonstrated that several pharmacologic agents accelerate recovery, several do not, and that certain types of mechanical and electrical stimulation to the muscles and nerves, respectively, both accelerate and improve recovery from facial nerve injury. Recent findings in the field of rehabilitation strongly suggest that robot- or computer-assisted rehabilitation methods improve motor recovery after neurologic injury, particularly when the elements of motivation and learning are introduced into the therapeutic paradigm. By incorporating data from the precise level of patient function at any given point in recovery, and assuring patient participation via motivational strategies, customized sensorimotor rehabilitation has proven more effective than simple passive assistance therapies, which provide mechanical assistance irrespective of the subject's level of function. In this proposal, we apply and compare several different rehabilitative modalities to the regenerating rodent facial nerve after both axonotmesis (crush) and neurotmesis (cut) injuries. We will delivery oral reward therapy through successive approximations, in order to introduce the motivational element demonstrated to be an important factor in human motor recovery. We will also deliver different forms of passive assistance therapy (mechanical stimulation) to denervated muscles. We will compare fixed-schedule passive assistance therapy with customized, dynamic passive assistance therapy designed to respond to the rodent's normal and recovering behavior (i.e. externally moving the rat's anatomy in concert with their intended motor output), and will also examine combinations of both modalities together. In addition, we will examine the effect of preserving facial muscle architecture, via coaptation of a sensory nerve to the denervated muscle, on overall recovery following facial nerve injury and repair.

Public Health Relevance

Peripheral nerve injuries are a source of enormous disability in the United States;the discovery of more effective ways of accelerating and improving recovery from these injuries would be of enormous benefit. Using a rodent model, we propose to employ computer-assisted, patient-specific sensory and motor rehabilitative therapy following facial nerve injury and repair, to measure its benefit and maximize its effect.

National Institute of Health (NIH)
National Institute of Neurological Disorders and Stroke (NINDS)
Research Project (R01)
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Acute Neural Injury and Epilepsy Study Section (ANIE)
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Jakeman, Lyn B
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Massachusetts Eye and Ear Infirmary
United States
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Chen, Pei; Knox, Christopher J; Yao, Linli et al. (2017) The effects of venous ensheathment on facial nerve repair in the rat. Laryngoscope 127:1558-1564
Weinberg, Julie S; Kleiss, Ingrid J; Knox, Christopher J et al. (2016) The Dilator Naris Muscle as a Reporter of Facial Nerve Regeneration in a Rat Model. Ann Plast Surg 76:94-8
Banks, Caroline A; Knox, Christopher; Hunter, Daniel A et al. (2015) Long-term functional recovery after facial nerve transection and repair in the rat. J Reconstr Microsurg 31:210-6
Bhama, Prabhat K; Weinberg, Julie S; Lindsay, Robin W et al. (2014) Objective outcomes analysis following microvascular gracilis transfer for facial reanimation: a review of 10 years' experience. JAMA Facial Plast Surg 16:85-92
Hohman, Marc H; Kleiss, Ingrid J; Knox, Christopher J et al. (2014) Functional recovery after facial nerve cable grafting in a rodent model. JAMA Facial Plast Surg 16:20-4
Heaton, James T; Sheu, Shu Hsien; Hohman, Marc H et al. (2014) Rat whisker movement after facial nerve lesion: evidence for autonomic contraction of skeletal muscle. Neuroscience 265:9-20
Hohman, Marc H; Kim, Sang W; Heller, Elizabeth S et al. (2014) Determining the threshold for asymmetry detection in facial expressions. Laryngoscope 124:860-5
Frigerio, Alice; Hadlock, Tessa A; Murray, Elizabeth H et al. (2014) Infrared-based blink-detecting glasses for facial pacing: toward a bionic blink. JAMA Facial Plast Surg 16:211-8
Kleiss, Ingrid J; Knox, Christopher J; Malo, Juan S et al. (2014) Whisking recovery after automated mechanical stimulation during facial nerve regeneration. JAMA Facial Plast Surg 16:133-9
Knox, Christopher J; Hohman, Marc H; Kleiss, Ingrid J et al. (2013) Facial nerve repair: fibrin adhesive coaptation versus epineurial suture repair in a rodent model. Laryngoscope 123:1618-21

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