Nerve Regeneration Process Research Articles

Differentiating astroglia in nervous tissue histogenesis/regeneration: studies in a model system of regenerating peripheral nerve.

The role of astroglia in nervous system histogenesis/regeneration (morphogenesis) was studied as a function of cell age. The effect of inoculated astroglia at different cell maturation stages on axonal growth was examined in a peripheral nerve regenerating model system. This model system consists of rat sciatic nerve stumps that regenerate through an empty silicone chamber (Lundborg et al.: Journal of Neuropathology and Experimental Neurology 41:412-422, 1982). Rat astroglial cell populations grown in cell culture were suspended either in a liquid (physiological solution) or in a solid (isotonic collagen gel) medium and inoculated within the silicone chamber at the time of surgery. Immature and mature cell populations, at ages corresponding to 9-69 postnatal days (P9-P69), were inoculated, and their effect on neural growth was analyzed by histological, immunocytochemical, and ultrastructural techniques, 2-6 weeks later. Astroglial cells differentially modulated the process of nerve regeneration, an effect that is a function of the cells' developmental stage. P19 astroglia and older cells inhibited the regeneration process, encapsulating the axons in a glia-limitans-like structure. Immature astrocytes (P9) did not seem to interfere with the regeneration process; nerve outgrowth in their presence resembled and was comparable to the ones obtained in the presence of inoculated Schwann cells. The differential effects of the developing astroglia were not significantly changed by the inoculation media, e.g., liquid or solid, and were already pronounced 2 weeks after neural transection. It is suggested by the results of the study that the role and function of astroglia in nervous system morphogenesis are changing with cell differentiation. Adult astrocytes seem to downregulate axonal growth; presumably, their function is to confine the neurites within designated structural and functional boundaries.

低出力レーザー照射のラット坐骨神経に及ぼす影響

The effect of low power laser irradiation on rat sciatic nerve was examined.Kept wet with saline, the sciatic nerves were exposed unilaterally, and irradiated by CO2 laser (12J/cm2, 24J/cm2), directly. All the time, the electrophysiological changes of evoked nerve action potential were observed.Immediately after CO2 laser irradiation, nerve conduction accelerated (12J/cm2), and suppressed (24J/cm2). The temperature in the nerve rose to about 45°C (24J/cm2), and nerve conduction was blocked (>24 J/cm2).So the process of nerve regeneration was examined by compared two methods, i. e., the crush of 1 mm in length and the end to end suture after transection.In the result, the regeneration of laser irradiation group was faster than the others. And the main effect of low power CO2 laser seemed to be the heat effect.In addition, the effects of Ga-Al-As diode laser and He-Ne laser irradiation on rat sciatic nerves were observed. No clear change in nerve conduction could be observed after irradiation.

Chapter 29 The reinnervation of denervated skin

This chapter discusses the reinnervation of denervated skin. The regeneration of peripheral nerves in man is frequently associated with undesirable sequelae referred to as paresthesias or dysesthesias. Paresthesias and dysesthesias are abnormal sensations in the skin in response to stimuli that, ordinarily, are not unpleasant. The sensations can involve thermal as well as tactile stimuli and can be quite unpleasant. Vibrissae are specialized large hairs surrounded by erectile tissue that are innervated by numerous sensory terminals arranged in a pattern that is much more complex than that of guard hairs. The other sensory innervation of vibrissae is derived from the superficial dermal nerve plexus and provides the source of nerves innervating the conus region of the sinus (the apex of the sinus) as well as the Merkel rete ridge collar that surrounds the hair as it emerges from the skin surface. The key to understanding the limits of sensory regeneration is the understanding about the process of normal development. The processes of nerve regeneration and nerve development can never be the same.

Nerve regeneration through cryo-treated xenogeneic nerve grafts.

Cryo-treated nerves whose Schwann cells had been killed by repeated freezing and thawing were xenogenically grafted into sciatic nerves from rats (Wistar, as donor) to mice (ddy strain, as recipient) to examine whether Schwann cell basal lamina tubes of cryo-treated xenogeneic grafts were effective conduits for regenerating axons. For comparison and evaluation of the effectiveness of this technique, experiments using grafts without the cryo-treatment were carried out. Cells in cryo-treated xenografts degraded into cell debris immediately after grafting and then were phagocytized by macrophages. After the cellular components had been removed from the graft, Schwann cell basal laminae remained intact in situ, serving as conduits for the regenerating axons. The process of nerve regeneration was almost the same as that observed in cryo-treated auto- and allografts, except that the regeneration was slightly delayed in the xenogeneic graft. In contrast, an extensive cell infiltration occurred in the non-treated grafts. It appeared that the donors Schwann cells in the graft deteriorated due to immunological reactions and were finally eliminated by macrophages, leaving their basal laminae undamaged in situ. The initiation of nerve regeneration including perineurial sheath formation in non-treated grafts was, therefore, significantly delayed, but once begun, it proceeded in the same manner as in the cryo-treated grafts. These findings strongly indicate that Schwann cell basal laminae can serve as effective pathways for regenerating axons even in the xenograft. Moreover, cryo-treated xenogeneic grafts are more desirable than non-treated ones, since dead Schwann cells in the former can be removed in the early period (4-14 days) from the graft without causing any immunological reaction, thus resulting in the facilitation of nerve regeneration.

Nerve regeneration through allogenic nerve grafts in mice.

The purpose of this study was to examine whether the basal laminae of Schwann cells in allografts could survive immunological rejection and serve as a conduit for regenerating nerves, as in the case of autogenic nerve grafts. Allografts of nerves were carried out using sciatic nerves of mice after the grafts had been repetitively frozen to kill their Schwann cells. Two mouse strains, C57BL/6N and C3H/HeN, were used, as they are known to differ in major histocompatibility complex. The mid-portion of the grafted nerve segments was examined by electron microscopy. In addition, the toe pad skin and lumbrical muscles were examined for determining whether regenerating nerves reinnervate sensory end organs and motor endplates. The process of nerve regeneration in the allograft was the same as that seen in the autograft. Cells in the graft disintegrated into cell debris and were phagocytized by macrophages, whereas the basal laminae of Schwann cells were not removed by macrophages, remaining in the form of tubes or scaffolds. Regenerating nerve fibers grew out through such basal lamina scaffolds, keeping in contact with the inner surface. Digital sensory corpuscles and motor endplates of the operated side were well reinnervated. The results indicate that the basal laminae of Schwann cells of the allograft may survive and serve as a conduit for regenerating axons in the same way as in the case of an autograft.

The process of neurite formation and nerve regeneration

The process of neurite formation and nerve regeneration

Experimental study of bridging the peripheral nerve gap with skeletal muscle.

A piece of skeletal muscle was used as a conduit to bridge the gap microsurgically between the two ends of the severed sciatic nerve in 30 rats, and a method for histochemical demonstration of acetylcholinesterase was employed to assess the nerve regeneration process 5 weeks or more after the operation. Regenerating nerve fibers were detected in the muscle and could be traced through to the distal stump of the severed sciatic nerve. This suggests that skeletal muscle might serve as a grafting conduit for the repairing of peripheral nerve injuries.

Nerve regeneration through synthetic biodegradable nerve guides: regulation by the target organ.

The successful regeneration of a multifascicular, complete peripheral nerve through a tubular synthetic biodegradable nerve guide across a gap of 10 mm in the rat sciatic nerve is reported. The importance of the distal nerve as a source of target-derived neuronotrophic factors necessary for the successful regeneration of the proximal regenerating nerve is emphasized. A simplified research model for further investigation into and manipulation of the biological processes of nerve regeneration is described. The potential clinical utilization of this model in the management of peripheral nerve injuries and, ultimately, central nervous system lesions is mentioned.

Molecular events associated with increased regenerative capacity of the goldfish retinal ganglion cells following X-irradiation: Decreased level of axonal growth inhibitors

In our previous work we established conditions to study the contribution of non-neuronal cells to the process of goldfish optic nerve regeneration. This issue has been studied successfully by adapting the use of X-irradiation to manipulate division of non-neuronal cells associated with the injured nerve. The regenerative capacity of the goldfish retinal ganglion cells was determined subsequent to the X-ray treatment. In this work we present an analysis of the molecular events associated with regeneration and enhanced regenerative capacity which follows X-irradiation. Under normal conditions the non-neuronal cells surrounding an intact nerve released axonal growth inhibitors, the level of which was only slightly sensitive to X-irradiation. In contrast, regenerating nerves showed a marked decrease in substances having an inhibitory effect on sprouting in vitro. Moreover, their level was significantly reduced following X-irradiation which was accompanied by increased accumulation of fibrous collagen adjacent to astrocytes. The alteration in the reciprocal relationship between the axon and the surrounding non-neuronal cells was also manifested by changes in the profile of labeled proteins released by the non-neuronal cells. The results of this work, therefore, indicate the sensitivity of the retinal ganglion cells to environment provided by the cells surrounding the regenerating fibers and thus may open a new perspective relating to the capacity of neurons to regenerate.

Energy transfer and molecular switching II. Muscle contraction and enzymatic reactions.

Abstract In Part I (Barrett, 1981), the concept of chemical parametric excitation was reviewed and applied to the process of nerve action potential excitation and regeneration. In the present paper, the chemical reactions involved in muscle contraction and the enzymatic reaction are examined and shown to be examples of chemical parametric excitation. It is demonstrated that in a model biochemical scheme for an enzymatic reaction, the enzyme is activated from a state, X , to a state, X ∗ , and in this activated state pumps the reaction parametrically. The concept of enzyme is identified with an excited state or state of disequilibrium permitting a release of energy during the dissipation, X ∗ →X , in the enzymatic reaction, which is powered by the release of energy in the return to the unexcited state X . The demonstration of parametric excitation relations for chemical systems indicates an explanation for the directionality of energy flow and designates an energy pumping role for an enzyme. In muscle contraction, the role of X ∗ is played by actomyosin and Ca 2+ , and the enzymatic reaction is the hydrolysis of ATP. The release of energy caused by this hydrolysis reaction brings about the conformational changes underlying muscle contraction.

The effects of acute and chronic morphine treatment on the process of facial nerve regeneration

Prominent cellular responses to axonal interruption include enhanced synthesis of RNA and protein in the neuronal perikaryon, and proliferation of reactive Schwann cells. Since morphine has been shown to significantly depress cellular metabolism, we examined its effect on these and other reparative responses underlying nerve fiber regeneration. Rat facial nerve trunks from saline, acute morphine, and continous morphine-treated animals were examined by light and electron microscopy at 3, 7 and 14 days after crush injury. The number of axonal sprouts/unit area and the diameters of regenerating axons were quantified at each survival interval. Both saline-treated and acute morphine-treated facial nerves demonstrated myelin degradation and Schwann cell hypertrophy (at 3 days post-axotomy), sprout outgrowth (at 7 days) and axon maturation and myelination (at 14 days). In the chronic morphine-treated animals, a retardation of the regenerative process was evident. Axon sprout outgrowth and axonal diameters were reduced at 3 and 7 days post-axotomy. In treated 14-day animals, axon diameters were normal; however, significantly fewer axon profiles/unit area were observed. After chronic morphine exposure, Schwann cell hypertrophy and proliferation, as well as myelin debris removal, were inhibited at all survival periods.

The Effects of Acute and Chronic Morphine Treatment on the Process of Facial Nerve Regeneration

The Effects of Acute and Chronic Morphine Treatment on the Process of Facial Nerve Regeneration

NERVE REGENERATION IN REPLANTED CANINE LIMBS.

The conduction velocities in regenerating common peroneal and tibial nerves were determined in the replanted hind limbs of 12 dogs examined 3–29 months following operation. The velocities in the fastest nerve fibers (max. diam. 7–11 µ) were approximately 50% less than the velocities in the fastest fibers in nonoperated (control) limbs (max. diam. 15–20 µ). This degree of nerve regeneration was sufficient to provide useful extremities in these animals. There was persistent slowing of conduction velocity proximal to the site of transection, which was associated with a decrease in the number of large fibers. Conduction velocity was decreased distally in replanted limbs consistent with the process of centrifugal nerve regeneration. The velocity as well as the diameter of the nerve fibers did not return to normal even 29 months after replantation and was less than that reported after section and suture. This difference was probably related to the additional surgical trauma and temporary ischemia associated with amputation and replantation of the limb.

Investigations on the nature of peripheral factors influencing the process of motor nerve regeneration.

Journal of Comparative NeurologyVolume 99, Issue 3 p. 561-597 Article Investigations on the nature of peripheral factors influencing the process of motor nerve regeneration Daxiel Herbert Lodwick Evans, Daxiel Herbert Lodwick Evans Department of Anatomy, University College, LondonSearch for more papers by this author Daxiel Herbert Lodwick Evans, Daxiel Herbert Lodwick Evans Department of Anatomy, University College, LondonSearch for more papers by this author First published: December 1953 https://doi.org/10.1002/cne.900990306Citations: 11AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Citing Literature Volume99, Issue3December 1953Pages 561-597 RelatedInformation

NERVE REGENERATION IN THE RAT FOLLOWING TUBULAR SPLICING OF SEVERED NERVES

For many years a method for uniting severed nerves has been used in experiments in my laboratory which has proved so superior to the conventional suture methods that the possibility of adapting it to the surgical needs of human beings deserves serious consideration. While the studies pursued with this method have branched into many phases of the problem of nerve restoration, the following brief account will confine itself to those aspects which seem to be of immediate practical interest. The method consists in splicing the stumps of a severed nerve by inserting them in a closely fitting sleeve of live artery. First devised for use in the frog and toad1the method was then applied to the rat2and has lately been used extensively in work on this animal. Save for a brief note,3no special description of the technic and of the processes of nerve regeneration