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 regeneration ciliary 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. cntf has numerous trophic roles in motor neurons in the peripheral nervous system including the prevention of atrophy of dennervated tissue and the prevention of degeneration and death of motor neurons after nerve injury. (frostick) in sciatic motor neurons both cntf receptor mrna expression and cntf receptor is increased after injury for a prolonged time frame compared to the short time frame in the central nervous system suggesting a role for cntf in nerve regeneration. insulin-like growth factors (igfs) have been shown to increase the rate of peripheral nervous system axon regeneration. igf-i and igf-ii mrna levels are significantly increased distal to the site of crush injury in rat sciatic nerves. at the site of nerve repair, locally delivered igf-i can significantly increase the rate of axon regeneration within a nerve graft and help expedite functional recovery of a paralyzed muscle. role of neurite-promoting factors neurite promoting factors include many extracellular matrix proteins produced by schwann cells at the distal stump including fibronectin and laminin. fibronectin are components of the basal lamina and promote neurite growth and adhesion of the growth cone to the basal lamina. in regenerating neural cells, neurite promoting factors play a role in adhesion of the axon and include neural cell adhesion molecule (n-cam) and n-cadherin. treatment unless otherwise demonstrated, nerve injuries are commonly irreversible, and therefore complete treatment is rather difficult, though still possible and hence lifelong management of disabilities arising due to nerve injuries is necessary. nerve regeneration therapies main article: neuroregeneration electrical stimulation can promote nerve regeneration. 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. many other factors also affect nerve recovery. the use of autologous nerve grafting procedures that involve redirection of regenerative donor nerve fibers into the graft conduit has been successful in restoring target muscle function. localized delivery of soluble neurotrophic factors may help promote the rate of axon regeneration observed within these graft conduits. an expanding area of nerve regeneration research deals with the development of scaffolding and bio-conduits. scaffolding developed from bio-compatible material would be useful in nerve regeneration if they successfully exhibit essentially the same role as the endoneurial tubes and schwann cells do in guiding regrowing axons. prevention of nerve injuries methods to help prevent peripheral nerve injuries include injection pressure monitoring. the presence of a high opening injection pressure (> 20 psi) is a sensitive sign of intrafascicular/intraneural needle tip placement. extrafascicular needle tip placement is associated with low pressures (< 20 psi). also, high pressure injection was associated with neurologic deficits and severe axonal damage after the block. other methods of preventing peripheral nerve injury include electrical nerve stimulation and ultrasonography. electrical stimulation with a motor response at < 0.2 ma only can occur with an intraneural/intrafasciular needle tip location.