Peripheral Nerve Segments Research Articles

The Synthesis, Structural Characterization, and Receptor Specificity of the α-Conotoxin Vc1.1

The alpha-conotoxin Vc1.1 is a small disulfide-bonded peptide currently in development as a treatment for neuropathic pain. This study describes the synthesis, determination of the disulfide connectivity, and the determination of the three-dimensional structure of Vc1.1 using NMR spectroscopy. Vc1.1 was shown to inhibit nicotine-evoked membrane currents in isolated bovine chromaffin cells in a concentration-dependent manner and preferentially targets peripheral nicotinic acetylcholine receptor (nAChR) subtypes over central subtypes. Specifically, Vc1.1 is selective for alpha3-containing nAChR subtypes. The three-dimensional structure of Vc1.1 comprises a small alpha-helix spanning residues Pro6 to Asp11 and is braced by the I-III, II-IV disulfide connectivity seen in other alpha-conotoxins. A comparison of the structure of Vc1.1 with other alpha-conotoxins, taken together with nAChR selectivity data, suggests that the conserved proline at position 6 is important for binding, whereas a number of residues in the C-terminal portion of the peptide contribute toward the selectivity. The structure reported here should open new opportunities for further development of Vc1.1 or analogues as analgesic agents.

A conus peptide blocks nicotinic receptors of unmyelinated axons in human nerves

The novel alpha-conotoxin Vc1.1 is a potential analgesic for the treatment of painful neuropathic conditions. In the present study, the effects of Vc1.1 were tested on the nicotine-induced increase in excitability of unmyelinated C-fiber axons in isolated segments of peripheral human nerves. Vc1.1 in concentrations above 0.1 microM antagonized the increase in axonal excitability produced by nicotine; the maximal inhibition was observed with 10 microM. We also demonstrate immunoreactivity for alpha 3 and alpha 5 subunits of neuronal nicotinic receptors on unmyelinated peripheral human axons. Blockade of nicotinic receptors on unmyelinated peripheral nerve fibers may be helpful in painful neuropathies affecting unmyelinated sympathetic and/or sensory axons.

Peripheral Nerve Allografts Stored in Green Tea Polyphenol Solution

We previously demonstrated the successful 1-month storage of peripheral nerve segments in a green tea polyphenol extract. We investigated whether this method could reduce the donor-host immune reaction associated with peripheral nerve allotransplantation. Sciatic nerve segments (20 mm long) were harvested from Dark Agouti (DA) rats, stored in polyphenol solution (1 mg/mL) for 1 month, and transplanted into recipient major histocompatibility complex-mismatched Lewis rats to bridge 15-mm-long sciatic nerve gaps (polyphenol-treated allograft group). The controls were an isograft group (nerve segments harvested from Lewis rats were immediately transplanted into Lewis rats), a polyphenol-treated isograft group (nerve segments harvested from Lewis rats were treated by polyphenol in the same method and transplanted into Lewis rats), and a fresh allograft group (nerve segments harvested from DA rats were transplanted into Lewis rats without storage). To investigate the origins of the cells in the transplanted nerves, sciatic nerve segments harvested from the male DA rat donors were transplanted into female Lewis rat recipients; genomic DNA was extracted from each nerve segment and amplified by polymerase chain reaction using primers specific for the rat sex-determining region of the Y-chromosome (Sry). Nerve regeneration in the polyphenol-treated allograft group was similar to that in the isografted group. Sry-specific bands were detected in all samples in the sex-mismatched polyphenol-treated allograft specimens despite their major histocompatibility complex incompatibility. Storage in green tea polyphenol solution can reduce both ischemic damage to nerve tissue and donor-host immune reactions after allotransplantation.

Association between Helicobacter pylori infection and acute inflammatory demyelinating polyradiculoneuropathy

The aim of this study was to investigate a possible association between Helicobacter pylori infection and acute inflammatory demyelinating polyradiculoneuropathy (AIDP). Of 17 consecutive patients with Guillain-Barre syndrome (GBS), 13 patients (six females; mean age 50 +/- 24 years) with AIDP were investigated. Clinical status was evaluated according to Hughes' score, and electrophysiological tests were performed within 2 weeks from disease onset. Helicobacter pylori infection was detected histologically and serum H. pylori-specific IgG antibodies were analysed by ELISA. Twenty asymptomatic patients (12 females; mean age 63 +/- 8 years), undergoing upper gastrointestinal endoscopy for investigation of mild iron deficiency anaemia, served as controls. Helicobacter pylori was found in 12 of 13 AIDP patients (92%), and in 10 of 20 controls (50%), (P = 0.02). Electrophysiological studies showed demyelination in all AIDP patients. High levels of anti-H. pylori IgG antibodies correlated with advanced clinical status. Five of seven AIDP patients with high levels of anti-H. pylori IgG antibodies had delayed F-wave latencies, indicating affection of proximal segments of peripheral nerves. Helicobacter pylori infection seems to be more frequent in AIDP patients. Anti-H. pylori titre might reflect advanced clinical status. Anti-H. pylori IgG antibodies are also associated with involvement of the proximal parts of peripheral nerves in AIDP.

Skin denervation in type 2 diabetes: correlations with diabetic duration and functional impairments--a comment

Sir, We read with great interest the article by Shun et al . (2004) recently published in your journal. The authors report on a significant skin denervation and its correlations with diabetes duration and functional impairments. On nerve conduction studies, they observed abnormal findings in only ∼50% of diabetic patients. It is well known that conventional nerve conduction tests fail to detect function of the most distal part of sensory nerve fibres or receptors. Recently we reported on a neurophysiological pattern providing data on the most extreme segments of peripheral sensory nerves (Aprile et al ., 2003). During conventional orthodromic sensory conduction studies using submaximal stimulus intensity, a sensory response characterized by a morphology with two peaks (double peak potential) is observed; …

Further development of reconstructive and cell tissue-engineering technology for treatment of complete peripheral nerve injury in rats

In this work we evaluated the efficacy of biodegradable composite co-polymer guiding neurotube, based on tissue-engineering technology, for the treatment of complete peripheral nerve injury where the nerve defect is significant. The right sciatic nerve of 12 three-month-old rats was completely transected and peripheral nervesegment was removed. A 2.2-cm biodegradable co-polymer neurotube containing viscous gel (NVR-N-Gel) with survival factors, neuroprotective agents and Schwann cells was placed between the proximal and the distal parts of the transected nerve for reconnection a 2-cm nerve defect. The proximal and distal parts of the nerve were fixed into the neurotube using 10-0 sutures. Ultrasound observation showed growth of the axons into the composite neurotube 2 months after the surgery. Electrophysiological study indicated compound muscle action potentials in nine out of 12 rats, 2-4 months after peripheral nerve reconstructive surgery. The postoperative follow-up (up to 4 months) on the operated rats that underwent peripheral nerve reconstruction using composite co-polymer neurotube, showed beginning of re-establishment of active foot movements. The tube was dissolved and nerve showed complete reconnection. Histological observation of the nerve showed growth of myelinated axons into the site where a 2-cm nerve defect replaced by composite co-polymer neurotube and into the distal part of the nerve. In conclusion: (1) an innovative composite neurotube for reconstruction of significant loss of peripheral nerve segment is described; (2) a viscous gel, containing survival factors, neuroprotective agents and Schwann cells served as a regenerative environment for repair. Further investigations of this reconstructive procedure are being conducted.

ATF3 upregulation in glia during Wallerian degeneration: differential expression in peripheral nerves and CNS white matter

BackgroundMany changes in gene expression occur in distal stumps of injured nerves but the transcriptional control of these events is poorly understood. We have examined the expression of the transcription factors ATF3 and c-Jun by non-neuronal cells during Wallerian degeneration following injury to sciatic nerves, dorsal roots and optic nerves of rats and mice, using immunohistochemistry and in situ hybridization.ResultsFollowing sciatic nerve injury – transection or transection and reanastomosis – ATF3 was strongly upregulated by endoneurial, but not perineurial cells, of the distal stumps of the nerves by 1 day post operation (dpo) and remained strongly expressed in the endoneurium at 30 dpo when axonal regeneration was prevented. Most ATF3+ cells were immunoreactive for the Schwann cell marker, S100. When the nerve was transected and reanastomosed, allowing regeneration of axons, most ATF3 expression had been downregulated by 30 dpo. ATF3 expression was weaker in the proximal stumps of the injured nerves than in the distal stumps and present in fewer cells at all times after injury. ATF3 was upregulated by endoneurial cells in the distal stumps of injured neonatal rat sciatic nerves, but more weakly than in adult animals. ATF3 expression in transected sciatic nerves of mice was similar to that in rats. Following dorsal root injury in adult rats, ATF3 was upregulated in the part of the root between the lesion and the spinal cord (containing Schwann cells), beginning at 1 dpo, but not in the dorsal root entry zone or in the degenerating dorsal column of the spinal cord. Following optic nerve crush in adult rats, ATF3 was found in some cells at the injury site and small numbers of cells within the optic nerve displayed weak immunoreactivity. The pattern of expression of c-Jun in all types of nerve injury was similar to that of ATF3.ConclusionThese findings raise the possibility that ATF3/c-Jun heterodimers may play a role in regulating changes in gene expression necessary for preparing the distal segments of injured peripheral nerves for axonal regeneration. The absence of the ATF3 and c-Jun from CNS glia during Wallerian degeneration may limit their ability to support regeneration.

C-Jun expression in surviving and regenerating retinal ganglion cells: effects of intravitreal neurotrophic supply.

To investigate c-jun expression in surviving and axon-regenerating retinal ganglion cells (RGCs) and the effect of intravitreal neurotrophic supply on c-jun expression. All animals underwent optic nerve transection (ONT) 0.5 mm behind the eyeball. Some animals underwent a replacement of the optic nerve with an autologous sciatic nerve graft (SNG) to allow axonal regrowth. To provide a neurotrophic supply, a peripheral nerve (PN) segment or brain-derived neurotrophic factor (BDNF)/ciliary neurotrophic factor (CNTF) was applied intravitreally. The time course of c-jun expression was first examined in both surviving and regenerating RGCs. Then, c-jun expression was examined in surviving and regenerating RGCs 3 weeks after intravitreal BDNF/CNTF treatment. Animals with vehicle eye injection were used as the control. Fluorescent dye was used for retrograde labeling of surviving (applied behind the eyeball) and regenerating (applied at the distal end of the SNG) RGCs. All retinas were immunohistochemically stained for c-jun. c-Jun was not detected in normal RGCs, but weak expression was seen in surviving RGCs after ON injury. The proportion of c-jun-positive (+) RGCs among surviving cell population was 52.6% to 86.5% 2 to 6 weeks after ONT. Among regenerating RGCs, more than 80% expressed c-jun in all treatment groups, a proportion that was significantly higher after CNTF treatment (90.7%). In addition, c-jun expression was much stronger in intensity and the c-jun(+) nuclei were much larger in regenerating than in surviving RGCs. c-Jun expression in RGCs was upregulated after injury. Most regenerating RGCs were c-jun(+), and the intensity of c-jun expression was higher in regenerating than in surviving RGCs. CNTF also upregulated c-jun expression in RGCs.

Successful storage of peripheral nerve before transplantation using green tea polyphenol: an experimental study in rats

Green tea polyphenol is known to act as a buffer, reducing biological responses to oxidative stress. Several effects of polyphenol have been reported, such as protection of tissue from ischemia, antineoplasmic and anti-inflammatory effects, and suppression of arteriosclerosis. In this study, we investigated whether peripheral nerve segments could be kept viable in a polyphenol solution for 1 month. Sciatic nerve segments, 20 mm long, were harvested from Lewis rats and treated in three different ways before transplanting to recipient Lewis rats to bridge sciatic nerve gaps created by removal of 15-mm-long nerve segments. Group F: nerve segments were transplanted immediately after harvesting. Group P: nerve segments were transplanted after they had been stored in Dulbecco's Modified Eagle's Medium (DMEM) containing polyphenol for 7 days at 4°C and then in DMEM for 21 days at 4°C. Group M: nerve segments were stored in DMEM solution alone for 28 days at 4°C. Viability of the nerve segments was assessed by vital staining (calcein-AM/ethidium homodimer), by electron microscopy and by genomic studies before transplantation. Nerve regeneration was evaluated using electrophysiological and morphological studies 12 and 24 weeks after transplantation. Neural cell viability of the preserved nerve segments was confirmed in group P, in which the nerve regeneration was similar to that in group F and superior to that in group M. Peripheral nerve segments can be successfully preserved for 1 month using green tea polyphenol.

A new approach to CNS repair using chimeric peripheral nerve grafts.

We have examined whether transplanted freeze-thawed peripheral nerve (PN) sheaths repopulated ex vivo with purified adult Schwann cells (SCs) support the regeneration of adult rat retinal ganglion cell (RGC) axons. Cultured adult SCs were derived from donor rats or from the host animals themselves. We also transplanted PN sheaths filled with neonatal SCs or donor adult olfactory ensheathing glia (OEG). 100,000 cells were injected into 1.5-cm lengths of freeze-thawed PN. After 2 days in culture, repopulated PN segments were grafted onto the transected optic nerve of adult Fischer rats. Three weeks later, 6% fluorogold (FG) was applied to distal PN. Retrogradely labeled RGCs were counted in retinal wholemounts and PN grafts were processed for immunohistochemistry. As expected, there was no RGC axon regeneration in cell-free grafts. Regrowth was also absent in neonatal SC- and adult OEG-filled grafts, which contained only small numbers of surviving donor cells. Many cells were, however, seen in adult SC repopulated PN grafts, intermingled with pan-neurofilament(+) and GAP-43(+) fibers. SCs were aligned along the grafts and were S-100(+), p75(+). Ultrastructurally, SCs were associated with myelinated and unmyelinated axons. Hundreds of FG-labeled RGCs were seen in retinas of rats with congeneic or allogeneic PN sheaths repopulated with either donor or autologous (host-derived) adult SCs. Intraocular CNTF injections significantly increased the number of regenerating RGCs in donor and autologous adult SC groups. The use of chimeric grafts to bridge CNS tissue defects could provide a clinical alternative to using multiple PN autografts, the harvesting of which would exacerbate peripheral dysfunction in already injured patients.

Peripheral nerve grafts and aFGF restore partial hindlimb function in adult paraplegic rats.

The purpose of this study was to evaluate the degree of functional recovery in adult rats with completely transected spinal cord following experimental treatment regimens that include implantation of peripheral nerve segments and local application of acidic fibroblast growth factor (aFGF). Rats were randomly divided to five groups: (1) spinal cord transection, (2) spinal cord transection and aFGF treatment, (3) spinal cord transection and peripheral nerve grafts, (4) spinal cord transection, aFGF treatment, and peripheral nerve grafts, and (5) sham control (laminectomy only). The locomotor behavior of all rats was analyzed by the Basso, Beattie and Bresnahan (BBB) open field locomotor test over the six months survival time. Immunohistochemisty for neurofilament protein, and somatosensory (SSEP) and motor evoked potentials (MEP) were used to evaluate axon growth across the damage site following the different treatments. The results show four principal findings: (1) Only the combination of peripheral nerve grafts and aFGF treatment improved hindlimb locomotor function after spinal cord transection. (2) The SSEP and MEP demonstrated electrophysiological evidence of both sensory and motor information crossing the damaged site, but only in the combined nerve grafts and aFGF treatment rats. (3) Immunostaining demonstrated neurofilament positive axons extending through the graft area and into distal end of spinal cord, but only in the group with combined nerve grafts and aFGF treatment. (4) Retransection of group 4 rats eliminated the behavioral recovery, MEP, and SSEP responses, indicating that the improvement of hindlimb locomotor activity came from supraspinal control. These results demonstrate the ability of the repair strategy combining peripheral nerve grafts and aFGF treatment to facilitate the regeneration of spinal ascending and descending tracts and also recovery of motor behavior following spinal cord injury.

Combination of gonadal steroid treatment and peripheral nerve grafting results in a peripheral motoneuron-like pattern of beta II-tubulin mRNA expression in axotomized hamster rubrospinal motoneurons.

Rubrospinal motoneurons (RSMN) represent a population of androgen receptor-containing central motoneurons in rodents. In this study, the ability of testosterone propionate (TP), alone or in conjunction with a peripheral nerve graft (PNG), to alter the molecular program of injured RSMN was accomplished using betaII-tubulin cDNA probes and quantitative in situ hybridization (ISH). Initial fluoro-gold labeling experiments following a T1 hemisection established that, as in the rat, the hamster rubrospinal system is essentially crossed and that injured RSMN concentrate in the ventrolateral region of the red nucleus. In the second experimental series, adult gonadectomized male hamsters were subjected to a right T1 hemisection, with half of the operated animals immediately subcutaneously implanted with 1 10 mm TP Silastic capsule and the other half sham implanted. In a third experimental series, animals were subjected to T1 hemisection, followed by transplantation of a predegenerated autologous segment of peripheral nerve. Half of the animals in each group received TP implants at the time of spinal cord injury and PNG. Postoperative times were 2, 7, and 14 days (dpo). Quantitative ISH was performed using a betaII-tubulin-specific (33)P-labeled cDNA probe, emulsion autoradiography, and computerized image analysis for grain counting. Injury alone resulted in a short-lived increase in betaII-tubulin mRNA expression in the RSMN at 2 dpo, with a significant decline to well below control values at 7 and 14 dpo. TP treatment or PNG alone attenuated, but did not prevent, the down-regulation of betaII-tubulin mRNA. In contrast, the combination of TP with a PNG sustained the injury-induced increase in betaII-tubulin mRNA levels throughout the postoperative period of 2, 7, and 14 dpo. The synergistic effects of the two treatment strategies confirm the importance of targeting multiple aspects of the injury response for therapeutic intervention.

Chapter 33 Reinnervation of the pretectum in adult rats by regenerated retinal ganglion cell axons: anatomical and functional studies

We have investigated the specificity of reinnervation and terminal arborization of injured retinal ganglion cell (RGC) axons in the brainstem with the object of studying in a simple situation the degree to which regenerating axons are able to replicate the characteristic patterns of terminal arborization and restore normal function. We have focussed here on the pathway that is responsible for the pupillary light reflex, which is mediated through the olivary pretectal nucleus (OPN). In adult rats, the left optic nerve was transected and a segment of peripheral nerve (PN) graft was used to bridge between the retina and different regions of the ipsilateral brainstem, including the superior colliculus. After 4-13 months, regenerated RGC axons were examined in coronal sections stained for cholera toxin B subunit. RGC axons were found extending into the ipsilateral brainstem for distances of up to 6 mm. Within the pretectum, axons innervated the OPN and the nucleus of the optic tract preferentially, and formed distinctive terminal arbors within each. Within the SC axons extended laterally into the visual layers and formed a different type of arborization. On testing the pupillary light reflex, it was found in best cases to show response amplitudes which were comparable to those recorded from control intact animals. However, unlike normals, the response amplitude tended to diminish with repeated stimulation and also appeared to deteriorate with age, although responses could still be detected in some cases as long as 15 months after grafting. These results indicate that regenerating axons can selectively reinnervate denervated nuclei, where they form typical terminal arborizations, and provide the substrates for restoring functional circuitry.

Evaluación neurofisiológica de los niños con neuropatías periféricas

The purpose of this review is to demostrate the value and limitations of neurophysiological evaluation of children with peripheral neuropathy. The neurophysiological evaluation (NPE) is an extension of the neurologic examination. The NPE has a high diagnostic sensitiviy but lacks etiologic specificity. The NPE includes motor and sensory nerve conduction velocity studies (NCV), needle EMG, somatosensory evoked potential (SEP) and motor evoked potential (MEP). The NCV allows to determine the component of the peripheral nerve fiber involved (axon and/or myelin), type of fibers affected (motor and/or sensory), the location of the lesion (proximal and/or distal) and the pattern of the nerve involvement (segmental or continuos). The EMG allows to determine the presence and degree of denervation and reinervation. The combination of NCV, EMG, SEP and MEP allow: 1. To localize a lesion to the diferent regions of the peripheral nervous system (preganglionic and/or postganglionic segments of dorsal root, ventral root, spinal nerve, plexus and peripheral nerves); 2. To determine severity and prognosis; 3. To select candidates for reconstructive exploratory surgery; and 4. To determine treatment efficacy and/or natural course of the disease

Spinal Nerve Segmentation in the Chick Embryo: Analysis of Distinct Axon-Repulsive Systems

In higher vertebrates, the segmental organization of peripheral spinal nerves is established by a repulsive mechanism whereby sensory and motor axons are excluded from the posterior half-somite. A number of candidate axon repellents have been suggested to mediate this barrier to axon growth, including Sema3A, Ephrin-B, and peanut agglutinin (PNA)-binding proteins. We have tested the candidacy of these factors in vitro by examining their contribution to the growth cone collapse-inducing activity of somite-derived protein extracts on sensory, motor, and retinal axons. We find that Sema3A is unlikely to play a role in the segmentation of sensory or motor axons and that Ephrin-B may contribute to motor but not sensory axon segmentation. We also provide evidence that the only candidate molecule(s) that induces the growth cone collapse of both sensory and motor axons binds to PNA and is not Sema3A or Ephrin-B. By grafting primary sensory, motor, and quail retinal neurons into the chick trunk in vivo, we provide further evidence that the posterior half-somite represents a universal barrier to growing axons. Taken together, these results suggest that the mechanisms of peripheral nerve segmentation should be considered in terms of repellent molecules in addition to the identified molecules.

Survival of axotomized retinal ganglion cells in peripheral nerve-grafted ferrets

Peripheral nerve (PN) grafting to the optic nerve stump stimulates not only axonal regeneration of the axotomized retinal ganglion cells (RGCs) into the grafted PN but also their survival. The purpose of the present study was to determine the number, distribution, and soma diameter of only surviving RGCs without regenerated axons and surviving RGCs with regenerated axons in PN-grafted mammals. A segment of PN was grafted to the optic nerve stump of adult ferrets. Two months after the PN grafting, surviving RGCs with regenerated axons were retrogradely labeled with granular blue (GB) and stained with RGC-specific antibody C38. Surviving RGCs without regenerated axons were identified as C38-positive cells without GB labeling. Twenty-one percent of RGCs survived axotomy after PN grafting in the area centralis (AC), whereas 47% survived in the peripheral retina. Twenty-six percent of surviving RGCs in the AC exhibited axonal regeneration, which was higher than that in the peripheral retina. Soma diameter histograms revealed that RGCs with regenerated axons showing both GB and C38 positivity were in the large soma diameter ranges. In contrast, the soma diameter distribution of surviving RGCs that did not have regenerated axons showed a peak in the smaller soma diameter ranges. The present data suggest that PN grafting promotes survival of axotomized RGCs more effectively in the peripheral retina than in the AC. Among surviving RGCs, the larger cells exhibited axonal regeneration into the grafted PN, whereas the axons of smaller cells did not to regenerate in either the AC or the peripheral retina.

Environmental Light Enhances Survival and Axonal Regeneration of Axotomized Retinal Ganglion Cells in Adult Cats

A segment of peripheral nerve was transplanted to the cut stump of the optic nerve to facilitate axonal regeneration of retinal ganglion cells (RGCs) in adult cats. The cats were reared under different light environment: 12 h light–12 h darkness, additional flash light under conventional light cycle, or 24 h darkness. After 60 days, the density and morphology of RGCs with regenerated axons were examined with retrograde labeling by fluoro-ruby and intracellular injections of Lucifer Yellow. In the retina of cats reared in darkness, densities of RGCs with regenerated axons were 11–42% of those in the retina of cats reared under conventional light and dark cycle. More than half of the labeled RGCs were degenerative in the retina of cats reared in darkness, while most RGCs were normal under conventional environment or flash light. We conclude that environmental light is essential for the survival and axonal regeneration of axotomized RGCs.

Bidirectional communication of sensory afferent information in a peripheral nerve of the cat forelimb.

Kinaesthetic information is derived from both muscle and joint nerves. However, the segregation, at peripheral levels, of inputs from these sources is by no means clear cut. In the present report, we demonstrate the complexity of peripheral innervation of joint and muscle structures in the cat's forearm, in particular, with evidence for bidirectional signalling for different classes of kinaesthetic afferents within a peripheral nerve segment. Three-way simultaneous recordings were carried out in the anaesthetized cat from single kinaesthetic afferents in three nerves that were freed from nearby tissue in the distal forearm, but remained in continuity. These were the wrist-joint nerve and two components of the indicis proprius nerve, one that projects proximally from the muscle to join the deep radial nerve, the other a distal extension of this nerve that runs through and beyond its own muscle to the region of the wrist-joint capsule where it forms an anastomosis with the wrist-joint nerve. Single-unit recording from the intact nerves demonstrated that some spindle afferent fibres from the indicis proprius muscle may take an "ectopic" path to the central nervous system, conveying their signals over an initial centrifugal path via the distal extension of the indicis proprius nerve, before looping back to project centripetally via the "classic" wrist-joint nerve. As some wrist-joint afferents themselves may project "ectopically" via the distal and then proximal segment of the indicis proprius nerve (rather than via the wrist-joint nerve), the recordings demonstrate that, within the distal segment of the indicis proprius nerve, there is bidirectional traffic of kinaesthetic afferent signals, with wrist-joint impulses travelling centripetally and muscle afferent signals travelling centrifugally. The findings emphasize the complexity of signalling that may be present in sensory nerves, on account of the "ectopic" paths taken by some afferents, and the need to activate deep inputs of joint or muscle origin by natural stimulation of the appropriate receptors in order to examine selectively the central actions and processing of either source of input.

Regenerative sprouting of retinal ganglion cells of adult hamsters induced by the epineurium of a peripheral nerve

Although it is known that transplantation of a peripheral nerve (PN) to the damaged central nervous system (CNS) promotes axonal regeneration, the interactions of cellular components of the PN with CNS neurons are still not well defined. Schwann cells in the PN are thought to be the major element involved in supporting CNS regeneration, but very little information exists with regard to whether other PN components also play an active role. Using our previously established model of transplanting a PN segment into the vitreous to stimulate regenerative sprouting of retinal ganglion cells (RGCs), we found that the epineurium isolated from a PN which had been pre-injured by transection was able to induce RGC sprouting when implanted intravitreally. Since the epineurium is composed mainly of connective tissue components and is devoid of Schwann cells, our results suggest that other cellular elements of the PN besides Schwann cells may have the potential to support CNS regeneration.

Link between optic nerve regrowth failure and macrophage stimulation in mammals

The adult mammalian central nervous system (CNS) fails to regenerate its axons following injury. A comparison between its postinjury response and that of axons of nervous systems capable of regeneration reveals major differences with respect to inflammation. In regenerative systems, a large number of macrophages rapidly invade the injured site during the first few hours and days after the injury. Following their activation/differentiation through interaction with the host tissue, they play a central role in tissue healing through phagocytosis of cell debris and communication with cellular and molecular elements of the damaged tissue. Relative to the peripheral nervous system (PNS), macrophage recruitment in the adult mammalian CNS is delayed and is restricted in amount and activity. It was recently proposed that in injured mammalian CNS tissue, implantation of macrophages stimulated by prior co-culture with segments of peripheral (sciatic) nerves can compensate, at least in part, of the restricted postinjury inflammatory reaction. In the present study, this experimental paradigm is further explored and shows that there is no conflict between the systemic use of anti-inflammatory compounds and treatment with stimulated macrophages to promote regrowth of neuronal tissue.