Peripheral Nerve Injury Modulates Neurotrophin Signaling in the Peripheral and Central Nervous System

Peripheral nerve injury disrupts the normal functions of sensory and motor neurons by damaging the integrity of axons and Schwann cells. In contrast to the central nervous system, the peripheral nervous system possesses a considerable capacity for regrowth, but regeneration is far from complete and functional recovery rarely returns to pre-injury levels. During development, the peripheral nervous system strongly depends upon trophic stimulation for neuronal differentiation, growth and maturation. The perhaps most important group of trophic substances in this context is the neurotrophins (NGF, BDNF, NT-3 and NT-4/5), which signal in a complex spatial and timely manner via the two structurally unrelated p75^NTR and tropomyosin receptor kinase (TrkA, Trk-B and Trk-C) receptors. Damage to the adult peripheral nerves induces cellular mechanisms resembling those active during development, resulting in a rapid and robust increase in the synthesis of neurotrophins in neurons and Schwann cells, guiding and supporting regeneration. Furthermore, the injury induces neurotrophin-mediated changes in the dorsal root ganglia and in the spinal cord, which affect the modulation of afferent sensory signaling and eventually may contribute to the development of neuropathic pain. The focus of this review is on the expression patterns of neurotrophins and their receptors in neurons and glial cells of the peripheral nervous system and the spinal cord. Furthermore, injury-induced changes of expression patterns and the functional consequences in relation to axonal growth and remyelination as well as to neuropathic pain development will be reviewed.     

Peripheral Nerve Phospholipid Composition: Development in Normal Nerve and Age-Dependent Changes in Wallerian Degenerated Nerve

Abstract: The phospholipid composition of normal peripheral nerve as a function of developmental age as well as that of Wallerian-degenerated nerve as a function of age at nerve transection and duration of Wallerian degeneration have been quantitated in rabbit sciatic nerve. During development, increases in the proportions of ethanolamine plasmalogen, sphingomyelin, and combined phosphatidyl serine plus phosphatidyl inositol and decreases in the proportions of phosphatidyl choline and phosphatidyl ethanolamine correlated well with the concurrent myelin accretion. During Wallerian degeneration, age-dependent changes in phospholipid composition were observed. The large and statistically significant increase in the proportion of phosphatidyl choline and decrease in the proportion of ethanolamine plasmalogen were manifest promptly in nerves transected at 2 weeks of age but in a delayed manner in nerves transected at 8, 12, and 20 weeks of age. The rate of loss of individual phospholipids was greater in nerves transected at younger ages. The findings from normal developing peripheral nerve may well serve as baseline data for subsequent studies of phospholipid composition in pathological peripheral nerve. The Findings from Wallerian-degenerated peripheral nerve provide additional evidence for age-dependent chemical changes occurring in Wallerian-degenerated peripheral nerve that may be of significance in explaining the superior functional recovery from peripheral nerve injury observed in younger compared with older subjects.     

Effective Gene Transfer into Regenerating Sciatic Nerves by Adenoviral Vectors: Potentials for Gene Therapy of Peripheral Nerve Injury

Replication defective adenoviral vectors have been demonstrated as an effective method for delivering genes into a variety of cell types and tissues both in vivo and in vitro. Transfecting genes into neuronal cells has proven to be difficult because of their lack of cell division. Since the major problem in neurological disease is the degeneration of the terminally differentiated neuronal cells, the adenoviral vectors ability to transfer genes into differentiated post-mitotic cells makes them advantageous for a gene delivery system for the nervous system. Here we showed that a replication defective recombinant adenovirus carrying the lacZ gene could infect the neuronal stem cells and even the differentiated neuronal cells derived from the central nervous system. The lacZ gene delivered into the neuronal cells was expressed efficiently. In addition, the recombinant virus also infected Schwann cells in intact and injured nerves in vivo. The expression of the lacZ gene lasted for 5 weeks, within which nerve regeneration is accomplished in the rat. Adenoviral vectors might thus be used to modulate Schwann cell gene expression for treating peripheral nerve injury or peripheral neuropathy.     

Techniques for Imaging Vascular Supply of Peripheral Nerves

Few studies have been developed to map the vascular structures feeding peripheral nerves, with the majority using cadaveric models and inadequate sample sizes. Preliminary evidence, while limited, indicates that the mapping of these vessels may allow or preclude certain procedures in nerve reconstruction due to the location of essential arterial inflow to the vasa nervorum. This review evaluates the evidence regarding historical, current, and emerging techniques for visualizing these vascular structures in vivo and considers their potential application in peripheral nerve vasculature.