The positive effect of electrical stimulation on nerve regeneration is due to its molecular influence on the damaged neuron and Schwann cells. Electrical stimulation can directly accelerate the expression of cyclic adenosine monophosphate (cAMP) both in neurons and Schwann cells. cAMP is a molecule that stimulates multiple signaling pathways that aid nerve regeneration by enhancing the expression of several neurotrophic factors. Electrical stimulation also results in the influx of calcium ions, which further triggers multiple regeneration pathways.The frequency of stimulation is an important factor in the success of both quality and quantity of axon regeneration as well as growth of the surrounding myelin and blood vessels that support the axon. Histological analysis and measurement of regeneration showed that low frequency stimulation had a more successful outcome than high frequency stimulation on regeneration of damaged sciatic nerves.Other studies have used both oscillating current (AC) and non-oscillating direct current (DC) stimulation to regenerate mammalian peripheral nerves. Mammalian neurons preferentially orient and grow towards the cathode in DC electric fields.Surgery can be done in case a nerve has become cut or otherwise divided. Recovery of a nerve after surgical repair depends mainly on the age of patients. Younger the patients, better the prognosis, because of better healing capacity of young tissues. Young children can recover almost normal nerve function. In contrast, a patient over 60 years old with a cut nerve in the hand would expect to recover only protective sensory function, that is, the ability to distinguish hot/cold or sharp/dull; recovery of motor function would be likely incomplete.
Neurotrophic factors act through retrograde transport in neurons, in which they are taken up by the growth cone of the injured neuron and transported back to the cell body. These neurotrophic factors have both autocrine and paracrine effects, as they promote growth of the damaged neurons as well as the adjacent Schwann cells. Nerve growth factor (NGF) typically has a low level of expression in nerves that are healthy and not growing or developing, but in response to nerve injury NGF expression increases in Schwann cells. This is a mechanism to increase growth and proliferation of Schwann cells at the distal stump in order to prepare for reception of the regenerating axon. NGF has not only a trophic role but also a tropic or guiding role. The Schwann cells that form the bands of Bungner at the distal injury site express NGF receptors as a guiding factor for the regenerating axon of the injured neuron. NGF bound to the receptors on Schwann cells provides the growing neurons that are contacted with a trophic factor to promote further growth and regenerationCiliary neurotrophic factor (CNTF) typically has a high level of expression in Schwann cells associated with nerves that are healthy, but in response to nerve injury CNTF expression decreases in Schwann cells distal to the injury site and remains relatively low unless the injured axon begins to regrow.