Erythropoietin enhanced recovery after peripheral nerve injury

<正>Peripheral nerve injuries are common disorders affecting the US population and represent a great economic and social burden.Acute injuries to peripheral nerves are most often due to an acute trauma or iatrogenic injury,with the resultant neurological deficit dependent on the injury type and severity.Clinical manifestations     

Delayed peripheral nerve repair: methods,including surgical ‘cross-bridging' to promote nerve regeneration

Despite the capacity of Schwann cells to support peripheral nerve regeneration, functional recovery after nerve injuries is frequently poor, especially for proximal injuries that require regenerating axons to grow over long distances to reinnervate distal targets. Nerve transfers, where small fascicles from an adjacent intact nerve are coapted to the nerve stump of a nearby denervated muscle, allow for functional return but at the expense of reduced numbers of innervating nerves. A 1-hour period of 20 Hz electrical nerve stimulation via electrodes proximal to an injury site accelerates axon outgrowth to hasten target reinnervation in rats and humans, even after delayed surgery. A novel strategy of enticing donor axons from an otherwise intact nerve to grow through small nerve grafts(cross-bridges) into a denervated nerve stump, promotes improved axon regeneration after delayed nerve repair. The efficacy of this technique has been demonstrated in a rat model and is now in clinical use in patients undergoing cross-face nerve grafting for facial paralysis. In conclusion, brief electrical stimulation, combined with the surgical technique of promoting the regeneration of some donor axons to ‘protect' chronically denervated Schwa nn cells, improves nerve regeneration and, in turn, functional outcomes in the management of peripheral nerve injuries.     

Platelet-rich plasma,an adjuvant biological therapy to assist peripheral nerve repair

hTerapies such as direct tension-free microsurgical repair or transplantation of a nerve autogratf, are now-adays used to treat traumatic peripheral nerve injuries (PNI), focused on the enhancement of the intrinsic regenerative potential of injured axons. However, these therapies fail to recreate the suitable cellular and molecular microenvironment of peripheral nerve repair and in some cases, the functional recovery of nerve injuries is incomplete. hTus, new biomedical engineering strategies based on tissue engineering approach-es through molecular intervention and scaffolding offer promising outcomes on the field. In this sense, evidence is accumulating in both, preclinical and clinical settings, indicating that platelet-rich plasma products, and ifbrin scaffold obtained from this technology, hold an important therapeutic potential as a neuroprotective, neurogenic and neuroinlfammatory therapeutic modulator system, as well as enhancing the sensory and motor functional nerve muscle unit recovery.     

Mesenchymal stem cell treatment for peripheral nerve injury: a narrative review

Peripheral nerve injuries occur as the result of sudden trauma and lead to reduced quality of life.The peripheral nervous system has an inherent capability to regenerate axons.However,peripheral nerve regeneration following injury is generally slow and incomplete that results in poor functional outcomes such as muscle atrophy.Although conventional surgical procedures for peripheral nerve injuries present many benefits,there are still several limitations including scarring,difficult accessibility to donor nerve,neuroma formation and a need to sacrifice the autologous nerve.For many years,other therapeutic approaches for peripheral nerve injuries have been explored,the most notable being the replacement of Schwann cells,the glial cells responsible for clearing out debris from the site of injury.Introducing cultured Schwann cells to the injured sites showed great benefits in promoting axonal regeneration and functional recovery.However,there are limited sources of Schwann cells for extraction and difficulties in culturing Schwann cells in vitro.Therefore,novel therapeutic avenues that offer maximum benefits for the treatment of peripheral nerve injuries should be investigated.This review focused on strategies using mesenchymal stem cells to promote peripheral nerve regeneration including exosomes of mesenchymal stem cells,nerve engineering using the nerve guidance conduits containing mesenchymal stem cells,and genetically engineered mesenchymal stem cells.We present the current progress of mesenchymal stem cell treatment of peripheral nerve injuries.     

NLRP3 inflammasome in retinal ganglion cell loss in optic neuropathy

正In neurodegenerative diseases,neuroinflammatory responses are often activated in resident immune cells in the central nervous system(CNS)(Schroder and Tschopp,2010).Optic neuropathy refers to dysfunction and degeneration of retinal ganglion cells(RGCs)and their axons,which is often induced by optic nerve injury or glaucomatous insult.Studies,     

Transforming growth factor beta 1, a cytokine with regenerative functions

We review the biology and role of transforming growth factor beta 1(TGF-β1) in peripheral nerve injury and regeneration, as it relates to injuries to large nerve trunks(i.e., sciatic nerve, brachial plexus), which often leads to suboptimal functional recovery. Experimental studies have suggested that the reason for the lack of functional recovery resides in the lack of sufficient mature axons reaching their targets, which is a result of the loss of the growth-supportive environment provided by the Schwann cells in the distal stump of injured nerves. Using an established chronic nerve injury and delayed repair animal model that accurately mimics chronic nerve injuries in humans, we summarize our key findings as well as others to better understand the pathophysiology of poor functional recovery. We demonstrated that 6 month TGF-β1 treatment for chronic nerve injury significantly improved Schwann cell capacity to support axonal regeneration. When combined with forskolin, the effect was additive, as evidenced by a near doubling of regenerated axons proximal to the repair site. We showed that in vivo application of TGF-β1 and forskolin directly onto chronically injured nerves reactivated chronically denervated Schwann cells, induced their proliferation, and upregulated the expression of regeneration-associated proteins. The effect of TGF-β1 and forskolin on old nerve injuries is quite impressive and the treatment regiment appears to mediate a growth-supportive milieu in the injured peripheral nerves. In summary, TGF-β1 and forskolin treatment reactivates chronically denervated Schwann cells and could potentially be used to extend and prolong the regenerative responses to promote axonal regeneration.     

Clinical potential of tensionlengthening strategies during nerve repair

A(very)brief history of tension in nerve repair:Successful nerve repair is achieved by conveying as many axons successfully to their targets as possible.Typically,this is best achieved through a direct end-to-end repair under minimal tension(Millesi,1986).However,this is not feasible in most cases of trauma,where a segment of tissue damage must be excised and overcome.This has most commonly been addressed with the use of nerve grafts to bridge the gap.Autologous nerve grafts are considered the gold standard,with allograft or synthetic substitutes demonstrating some success over shorter distances.Despite their utility,autologous grafts pose challenges of their own.These include functional deficit in the donor distribution(typically sensory),extended operative duration,additional scarring,and a lack of intrinsic blood supply.They are also a poor anatomical match for the stumps being bridged,both internally(disparate neuronal size and composition)as well as externally(often requiring cabled bundles to approximate the caliber of the nerve being repaired).Finally,unlike end-to-end repairs,autologous grafts also require axons to traverse a second repair interface,where a large proportion of axons are lost across the anatomical discontinuity.     

Effects of chemical and physical cues in enhancing neuritogenesis and peripheral nerve regeneration

正Peripheral nerve injuries are most often a consequence of axonal damage leading to functional losses that may vary from lack of sensitivity distal to the site of injury to complete loss of motor control.The consequences of such injuries are immense because of the high cost of health care,limited ability to work and emotional trauma that follows the injury.The spontaneous regrowth that the peripheral nervous system(PNS)     

Histological assessment in peripheral nerve tissue engineering

The histological analysis of peripheral nerve regeneration is one of the most used methods to demonstrate the success of the regeneration through nerve conduits. Nowadays, it is possible to evaluate different parameters of nerve regeneration by using histological, histochemical, immunohistochemical and ultrastructural techniques. The histochemical methods are very sensible and are useful tools to evaluate the extracellular matrix remodeling and the myelin sheath, but they are poorly specific. In contrast, the immunohistochemical methods are highly specific and are frequently used for the identification of the regenerated axons, Sehwann cells and proteins associated to nerve regeneration or neural linage. The ultrastructural techniques offer the possibility to perform a high resolution morphological and quantitative analysis of the nerve regeneration. However, the use of a single histological method may not be enough to assess the degree of regeneration, and the combination of different histological techniques could be necessary.     

Mesenchymal stem cell therapy for retinal ganglion cell neuroprotection and axon regeneration

<正>Retinal ganglion cells(RGCs)are responsible for propagating signals derived from visual stimuli in the eye to the brain,along their axons within the optic nerve to the superior colliculus,lateral geniculate nucleus and visual cortex of the brain.Damage to the optic nerve either through trauma,such as head injury,or degenerative disease,such as glaucoma causes irreversible loss of function