Ketogenic Diet Potentiates Electrical Stimulation–Induced Peripheral Nerve Regeneration after Sciatic Nerve Crush Injury in Rats

SCOPE: Recent findings indicate that the ketogenic diet (KD) is neuroprotective and electrical stimulation (ES) can improve functional recovery from peripheral nerve injury. However, it is not clear whether KD and ES play a synergistical role in the peripheral nerve recovery following injury. METHODS AND RESULTS: A KD consisting of a 3:1 ratio of fat to carbohydrate + protein is used and is coupled with ES treatment in a rat model of peripheral nerve crush injury. Neuromuscular recovery is evaluated by electromyography, and axonal regeneration and myelination by histological methods. The effects on insulin-like growth factor 1 (IGF-1) and IGF-1 receptor expression in peripheral nerve tissue, pre- and post-nerve injury, are also investigated. The combination of KD and ES synergistically increases muscle force in biceps femoris and gluteus maximus and prevents development of hypersensitivity in biceps femoris. It promotes peripheral nerve regeneration by increasing total axons, axon density, and axonal diameter, as well as myelin thickness and axon/fiber ratio. These effects are due to modulation of the IGF system as the treatment expression of IGF-1 and IGF-1 receptor in regenerated nerve tissue. CONCLUSION: The results establish that KD and ES promote peripheral nerve regeneration. Patients recovering from peripheral nerve injury may benefit from this combinational approach.