Restorative Neurology and Neuroscience - Volume 1, issue 3-4

Authors: Ingoglia, N.A. | Chakraborty, G. | Yu, M. | Luo, D. | Liu, C.

Article Type: Research Article

Abstract: Both axonal and glial components of nerve are capable of carrying out reactions in which Arg, Lys, Leu, Pro, Val, AJa and Ser can be covalently linked to endogenous proteins in reactions which require tRNA but occur in the absence of ribosomes and ribosomal RNA. These posttranslational protein modifications appear to play important roles in nerve regeneration since they are increased more than 10-fold within 2 h of a crush injury in nerves which are capable of regeneration, but are not activated in nerves not capable of regrowth following injury. The regulation of the modification of proteins by Arg and …Lys in vivo appears to be the function of separate peptides. The exogenous application of serine protease inhibitors (but not other protease inhibitors) mimics the effect of the endogenous peptides, suggesting that the endogenous regulators have serine protease inhibitory activity. The targets for modification are proteins of low abundance and thus far have been identified only in terms of their molecular weights and isoelectric points. The site of addition of Arg, but not the other amino acids, to target proteins is to the amino terminus. The addition of Arg to an amino terminus is likely to be involved in the ubiquitin mediated proteolysis of the modified protein. One of the most unusual findings in these series of experiments is that in regenerating sciatic nerves, amino acid modified proteins aggregate to form complexes of greater than 2 × 106 Da. The significance of this finding is not known. But we speculate that the aggregate may result from the assembly of an insoluble functional unit of the cell from soluble precursor proteins, and that the trigger for their assembly is amino acid modification. Show more

Keywords: Posttranslational modification, Amino acid, Sciatic nerve, Regeneration, tRNA

DOI: 10.3233/RNN-1990-13411

Citation: Restorative Neurology and Neuroscience, vol. 1, no. 3-4, pp. 245-252, 1990

Authors: Danielsen, Nils

Article Type: Research Article

Abstract: The silicone nerve regeneration chamber is a useful model to investigate the cellular and molecular events underlying successful regeneration in the peripheral nervous system. In this model a transected rat sciatic nerve with a 10-mm interstump gap, is repaired with a silicone chamber. The spatial-temporal sequence of regeneration in the silicone chamber has been examined in detail. The chamber rapidly becomes filled with fluid which contains neurotrophic activity for neurons in vitro. The second event to occur is the formation of a fibrin matrix connecting the two nerve stumps. This matrix is then invaded by cellular elements in the following …order: perineurial-like cells, vasculature, Schwann cells, and axons. The silicone chamber model also allows manipulation of the regeneration process. Prefilling the chamber at the time of implantation with phosphate-buffered saline or dialyzed plasma stimulates nerve regeneration. Multiple injections into the chamber of a mixture containing laminin, testosterone, and ganglioside GM1 increase the size and the vascularization of the regenerate. Specially designed chambers divided into two compartments by a longitudinally inserted nitrocellulose strip have been used to examine the effects of substrate-bound trophic factors on nerve regeneration. Fibroblast growth factor containing chambers have an improved regeneration and vascularization as compared to controls. Show more

Keywords: Silicone chamber, Nerve regeneration, Rat sciatic nerve, Neurotrophic factors, Fibrin matrix, Fibroblast growth factor

DOI: 10.3233/RNN-1990-13412

Citation: Restorative Neurology and Neuroscience, vol. 1, no. 3-4, pp. 253-259, 1990

Authors: Edström, Anders | Edbladh, Magnus | Ekström, Per | Remgård, Pär

Article Type: Research Article

Abstract: The adult frog sciatic nerve offers several advantages as an in vitro model to study nerve regeneration. The nerve with the attached dorsal root ganglia can easily be isolated and incubated in a culture medium for several days. If the nerve is subjected to a crush immediately after dissection there is a delay of 3.4 days after which the sensory axons start to regenerate into the distal nerve stump at a constant rate of about 1.1 mm · day−1 in serum-containing and 1.0 mm · day−1 in serum-free medium. Serum-free cultures may be used in future studies to …examine the effect of various neurotrophic factors. The existence of an accurate method for examining the outgrowth distance, based on axonal transport of labelled proteins, contributes to the attractiveness of the model. A compartmental culture system permits separate exposure of the ganglia and the nerve to different agents. Taking advantage of this, pharmacological studies suggest that Schwann cells produce signals, dependent on newly transcribed RNA, which transform the preparation into a growth state. The present model system offers favourable conditions to learn more about the early events and also the subsequent steps of the regeneration process. Show more

Keywords: Nerve regeneration, Sciatic nerve, In vitro, Adult frog

DOI: 10.3233/RNN-1990-13413

Citation: Restorative Neurology and Neuroscience, vol. 1, no. 3-4, pp. 261-266, 1990

Authors: Tonge, D. A. | Clarke, J. D. W. | Hunter, K. | Golding, J.

Article Type: Research Article

Abstract: Peripheral nerves and spinal cords of axolotls were maintained in organ culture for periods of up to 2 weeks. Sensory axons in peripheral nerves and the dorsal funiculus of the spinal cord showed regeneration through the crush site within about 2 days. Axonal regeneration also occurred in peripheral nerves after cutting but was dependent on close contact between proximal and distal stumps of nerve. When cells in the distal stump of nerve were killed by freezing, axonal regeneration was inhibited.

Keywords: Peripheral nerve, Spinal cord, Nerve regeneration

DOI: 10.3233/RNN-1990-13414

Citation: Restorative Neurology and Neuroscience, vol. 1, no. 3-4, pp. 267-273, 1990

Authors: Aldskogius, Håkan | Molander, Carl

Article Type: Research Article

Abstract: There are indications that specific factors are present in the distal stump of transected nerves which preferentially attract axons of the corresponding proximal stump into the distal nerve stumps. However, the impact of these factors is unclear, since there is abundant evidence that numerous regenerating motor and sensory axons are topographically misdirected after nerve transection and repair. Topographic reinnervation is improved after fascicular repair of fasciculated nerves, and quite precise after nerve crush. The latter may not be true, however, for non-myelinated axons, which show a high degree of aberrant growth even after crush. In contrast, regenerative outgrowth appears to …be topographically specific after neonatal nerve transection. Reinnervation of muscle fibers appears to be unspecific in adult mammals, but specific after neonatal injury under certain circumstances. Some preference for reinnervation of the appropriate sensory receptors seems to exist although this preference does not preclude reinnervation of receptors by ‘foreign’ sensory fibers. In conclusion, incorrect topographic and target reinnervation commonly occurs after peripheral regeneration in adult mammals, and most certainly explains some of the functional disturbances after peripheral nerve lesions. Topographic regeneration appears to be better after nerve injury in developing mammals indicating that mechanisms from the developmental period may persist and aid in accurate regenerative outgrowth. Show more

Keywords: Regeneration, Motor, Sensory, Adult, Development, Myelinated axon, Non-myelinated axon

DOI: 10.3233/RNN-1990-13415

Citation: Restorative Neurology and Neuroscience, vol. 1, no. 3-4, pp. 275-280, 1990

Authors: Brushart, Thomas M. E.

Article Type: Research Article

Abstract: Previous experiments have shown that motor axons regenerating in mixed nerve will preferentially reinnervate a distal motor branch. The present experiments examine the mechanism through which this sensory-motor specificity is generated. An enclosed 0.5 mm gap was created in the proximal femoral nerves of juvenile rats. Two, three or eight weeks later the specificity of motor axon regeneration was evaluated by simultaneous application of horseradish peroxidase (HRP) to one distal femoral branch (sensory or motor) and Fluoro-Gold to the other. Motoneurons were then counted as projecting (i) correctly to the motor branch, (ii) incorrectly to the sensory branch, and (iii) …simultaneously to both branches (double-labeled). Motor axon regeneration was random at 2 weeks, with equal numbers of motoneurons projecting to sensory and motor branches. However, the number of correct projections increased dramatically between 2 and 3 weeks. Twenty-six percent of neurons labeled at 2 weeks contained both tracers, indicating axon collateral projections to both sensory and motor branches. This number decreased significantly at each time period. Axon collaterals were thus ‘pruned’ from the sensory branch, increasing the number of correct projections at the expense of double-labeled neurons. These findings suggest random reinnervation of the distal stump, with specificity generated through trophic interaction between axons and the pathway and/or end organ. Show more

Keywords: Regeneration, Peripheral nerve, Neurotrophism, Double labeling, Axon collaterals, Selective pruning

DOI: 10.3233/RNN-1990-13416

Citation: Restorative Neurology and Neuroscience, vol. 1, no. 3-4, pp. 281-287, 1990

Authors: Carlstedt, T. | Risling, M. | Lindå, H. | Cullheim, S. | Ulfhake, B. | Sjögren, A. M.

Article Type: Research Article

Abstract: Spinal nerve root avulsion has been considered as a central nervous type of injury and therefore not repaired surgically in man. The possibility for axonal regeneration after root avulsion or root lesion has been investigated in laboratory animals by means of up to date neurophysiological, morphological and tracing techniques. It is shown that, after ventral root avulsion and implantation into the spinal cord, alpha and probably also gamma motoneurons are able to regenerate within the spinal cord for a considerable distance before entering the implanted root and reinnervate previously denervated skeletal muscles. The regenerated neurons were found to respond to …afferent activity with excitatory or inhibitory responses, and the regenerated axons could conduct action potentials that elicited muscle twitch responses. After dorsal root injury in the adult animal, regeneration into the spinal cord does not occur. However, regeneration of primary sensory neurons into appropriate locations of the spinal cord can be demonstrated in immature animals. Show more

Keywords: Spinal nerve root, Avulsion, Plexus injury, Neuron, Glia, Regeneration

DOI: 10.3233/RNN-1990-13417

Citation: Restorative Neurology and Neuroscience, vol. 1, no. 3-4, pp. 289-295, 1990

Authors: Lundborg, Göran

Article Type: Research Article

Abstract: Injuries to peripheral nerves represent a challenging clinical problem. In spite of the use of microsurgical techniques, repair of severed nerves seldom results in complete recovery of motor and sensory functions. Misdirection of axons at the suture line as well as a slow axonal outgrowth contribute to the bad results. Recent experimental data indicate that growth factors, synthesized by the damaged nerve tissue as well as protein-associated neurite-promoting factors in the local micro-environment play an important role for the regulation of axonal growth and directionality. Future studies should aim at an application of this knowledge to the clinical treatment of …nerve injuries. Show more

Keywords: Peripheral nerve, Nerve injury, Nerve repair, Nerve regeneration, Growth factors, Schwann cells

DOI: 10.3233/RNN-1990-13418

Citation: Restorative Neurology and Neuroscience, vol. 1, no. 3-4, pp. 297-302, 1990

Authors: Sisken, Betty F. | Kanje, Martin | Lundborg, Göran | Kurtz, Warren

Article Type: Research Article

Abstract: The influence of non-invasive, low level, pulsed electromagnetic fields (PEMF) on regeneration was tested on in vitro and in vivo models. Cultures of dorsal root ganglia were exposed to 2 Hz PEMF, amplitude of 0.05 mTesla while rats after a ‘crush’ lesion of sciatic nerves were exposed to 2 Hz PEMF, amplitude of 0.3 mTesla. In in vitro experiments, relative to controls, cultures treated with PEMF exhibited a significant increase in neurite outgrowth with dense labeling of neurons and neurites on autoradiographs after incorporation of [3 H]proline into new proteins. In vivo exposure of rats to PEMF for 3, 4 …or 6 days after lesioning produced a 22% increase in the regeneration rate relative to controls with no effect on the initial delay period. When rats were exposed to PEMF before lesioning without further treatment, the same degree of stimulation of axonal sprouting was obtained. Reduction of the amplitude from 0.3 mTesla to 0.06 mTesla eliminated this pre-exposure response. Alterations in the distribution of new proteins synthesized 2 weeks after PEMF treatment provide additional evidence for its influence at the whole body and cellular levels. Show more

Keywords: Pulsed electromagnetic field, Sensory ganglia culture, Neurite outgrowth, Crush lesion, Pinch test, Protein synthesis

DOI: 10.3233/RNN-1990-13419

Citation: Restorative Neurology and Neuroscience, vol. 1, no. 3-4, pp. 303-309, 1990