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Biomedical subjects

G Lundborg

Publications and source records attributed to G Lundborg.

At least 145 records · Page 8Linked to original sources

Vibration exposure and peripheral nerve fiber damage.

The hind leg of adult rats was exposed to vibrations (82 Hz; amplitude peak-to-peak 0.21 mm) for 4 hours during 5 consecutive days. Light and electron microscopic examination of the plantar and sciatic nerves were done immediately after the exposure period or after a 2- or 4-week recovery period. Light microscopic examination did not reveal any distinct signs of injury. However, ultrastructurally unmyelinated fibers in the plantar nerves showed distinct changes, with deranged axoplasmic structure and/or accumulation of smooth endoplasmatic reticulum. These changes were to a large extent reversible in 2 weeks and appeared normalized after a 4-week recovery period. No ultrastructural changes could be observed in the sciatic nerve. However, when the sciatic nerve was crushed after 5 days of vibration exposure, axonal outgrowth was increased 23% as compared with controls. These findings confirm that vibration induces nerve fiber damage, in this experimental model expressed as a "conditioning effect" contributing to increased regeneration potential of the corresponding neurones.

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Repair of osteochondral defects in the rabbit knee with Gore-Tex (expanded polytetrafluoroethylene). An experimental study.

In 28 knee joints in 14 rabbits 4 mm circular osteochondral defects were created in each medial femoral condyle. In 24 of the knee joints 4 mm Gore-Tex (E-PTFE) patches were glued into the defects with fibrin glue. Four joints were left without implants and served as controls. In 16 joints the membrane showed good macroscopic incorporation into the joint surface. In four joints the E-PTFE patches were lying loose. In the controls the defects were covered by thin irregular layers of reparative tissue. On histological examination at 12 weeks, cells were seen proliferating through the membrane and overlying its joint facing surface with the morphological appearance of the outer layers of the normal articular surface. We conclude that Gore-Tex might be of potential value in restoring the architecture of a damaged articular surface.

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Insulin-like growth factor I promotes nerve regeneration: an experimental study on rat sciatic nerve.

Insulin-like growth factor I (IGF-I; somatomedin C) has previously been demonstrated, with immunohistochemical methods, to accumulate locally at the site of trauma of an injured peripheral nerve. In the experiments reported here a Y-shaped silicone-chamber system was used to test if local infusion of IGF-I had supportive effects on nerve regeneration. The proximal end of a cut sciatic nerve was inserted into one channel of the Y-shaped chamber and the length and growth direction of the regenerating myelinated axons were evaluated after 1 month. When IGF-I (250 micrograms/ml 0.5 microliters/h) was infused into one channel by an osmotic pump, the length of the regenerating axons increased significantly compared to the control groups with no IGF-I added. In some instances the regenerating axons grew towards the osmotic pump. It is concluded that local infusion of IGF-I at appropriate concentration promotes regeneration of a peripheral nerve. It exerts a neuronotrophic but not a clear chemotactic effect.

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Insulin-like growth factor I (IGF-I) stimulates regeneration of the rat sciatic nerve.

The effect of insulin-like growth factor I (IGF-I) was tested on regeneration of the rat sciatic nerve after a crush lesion. IGF-I was administered via miniosmotic pumps to the dorsal root ganglia or locally around the crush lesion. Regeneration of sensory fibers was measured after 3 or 4 days superfusion by pinching. IGF-I stimulated regeneration in both administration paradigms. Regeneration was inhibited if the nerve was perfused with specific antibodies to native IGF-I. The results suggest that endogenous extracellular IGF-I plays an important role during regeneration of peripheral nerve fibers.

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Stimulation of rat sciatic nerve regeneration with pulsed electromagnetic fields.

The effects of pulsed electromagnetic fields (PEMF) on rat sciatic nerve regeneration after a crush lesion were determined. The rats were placed between a pair of Helmholtz coils and exposed to PEMF of frequency 2 Hz and magnetic flux density of 0.3 mT. A 4 h/day treatment for 3-6 days increased the rate of nerve regeneration by 22%. This stimulatory effect was independent of the orientation of the coils. Exposure times of 1 h/day-10 h/day were equally effective in stimulating nerve regeneration. Rats exposed to PEMF for 4 h/day for 7 days before crush, followed by 3 days after crush without PEMF, also showed significantly increased regeneration. This pre-exposure 'conditioning' effect suggests that PEMF influences regeneration indirectly.

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Regeneration of the rat sciatic nerve after different conditioning lesions: effects of the conditioning interval.

Regeneration of the rat sciatic nerve was studied after a crush lesion (test lesion) on nerves previously subjected to a conditioning lesion. The test lesion was made approximately 30 mm proximal to the conditioning lesion. The period between the conditioning lesion and the test lesion was varied. Regeneration was measured by the pinch test. The conditioning procedure increased the rate of axonal elongation and decreased the initial delay. Conditioning intervals between 14 hours and 4 days were sufficient to increase the regeneration distance significantly, but only until day 4. If the conditioning interval was prolonged to 7 or 14 days, the conditioning effect persisted until day 6. A conditioning effect also was produced by transection of the sciatic nerve and by local compression produced with a silicone tube. The results of this study demonstrate that the type of injury and the conditioning intervals are important determinants in producing the conditioning effect in the rat.

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Segmental variation in microstructure, matrix synthesis and cell proliferation in rabbit flexor tendon.

An experimental culture system was designed with the purpose of studying matrix synthesis and cell proliferation in the deep flexor tendon of the rabbit forepaw. Special attention was paid to differences between three consecutive defined segments of the tendon from the region of the tendon sheath. There were two fibrocartilaginous areas in the tendon, one in the dorsal part of the proximal segment and one in the volar part of the distal segment. The intermediate segment consisted of regular tendinous tissue. The dorsal aspect of the distal segment was further characterized by a cell rich area related to the entrance of the vinculum longum. Proteoglycan synthesis in vitro was higher in the proximal and distal segments than in the intermediate, while collagen synthesis was highest in the intermediate tendinous segment. Variations in collagen content were reflected in variations in collagen synthesis. The rate of cell proliferation was highest in the intermediate segment. Segmental biochemical characteristics correlated well with morphological variations of the deep flexor tendon. These variations may reflect an adaptation to different mechanical forces acting on the tendon. The segmental variations may also be relevant for the healing capacity of the flexor tendon.

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Tendon healing in vivo. An experimental model.

Flexor tendon segments were incubated in a diffusion chamber in the subcutis of rabbits. Tendons incubated up to 6 weeks in the diffusion chamber showed proliferating and migrating cells from the epitenon cell layer as well as viable endotenon cells. Explants frozen in liquid nitrogen prior to incubation showed no signs of extrinsic cell contamination and remained non-viable indicating that no cell penetration occurred through the Millipore filter and that cell division seen in non-frozen and incubated tendons was an expression of intrinsic cellular proliferative capacity of the tendon. In tendon segments incubated in chambers for three weeks, collagen synthesis was reduced by 50% and the rate of cell proliferation measured as 3H-thymidine incorporation, was 15 times that of native tendons. Frozen and incubated tendons showed only traces of remaining matrix synthesis or cell proliferation. With this experimental model we have histologically and biochemically shown that tendons may survive and heal while the nutrition exclusively could be based on diffusion and the tendons have an intrinsic capacity of healing. The described model enables further studies on tendon healing and its regulation.

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Finger receptor dysfunction in dental technicians exposed to high-frequency vibration.

The effects of high-frequency vibration (up to 40 kHz) on digital nerve function were studied in ten dental technicians and ten age-matched referents. Nerve conduction velocities, including fractionated antidromic measurements over the carpal tunnel, showed no difference between the groups. In the group of dental technicians the difference between the response latency of the mechanical and electric stimuli in the median nerve distally on the fingers of the right hand was slightly higher than in the reference group, and therefore distal nerve or receptor dysfunction was suggested. Vibration warming and cooling thresholds were significantly increased and thus revealed damage to both myelinated and unmyelinated fibers in the fingers of subjects exposed to high-frequency vibration.

Adult↗

Effects of growth hormone treatment on the regeneration of rat sciatic nerve.

The effect of human growth hormone (hGH) on regeneration of neuronal tissue have been studied in rats. A crush lesion was made on the sciatic nerve at the thigh level in intact or hypophysectomized rats. The hGH was administered systemically via subcutaneously implanted miniosmotic pumps. Regeneration was evaluated by the 'pinch-test' after 3, 4 and 6 days. Regeneration was significantly (P less than 0.05) impaired in hypophysectomized rats, but restored to normal after treatment with hGH (200 mIU/day). In intact rats treatment with 400 mIU/day hGH significantly (P less than 0.05) stimulated regeneration, whereas no effect was observed at 200 mIU/day. Immunoreactive insulin-like growth factor 1 (IGF-1) decreased in hypophysectomized rats, but rose again after hGH treatment. However, no consistent correlation between circulating IGF-1 and the rate of regeneration was found. Our results show that hGH can increase the rate of regeneration in peripheral nerves after injury. This can be due either to direct effects of hGH or to indirect effects via locally produced growth factors (e.g. somatomedins).

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A new method for studies of the effects of locally applied drugs on peripheral nerve regeneration in vivo.

An in vivo technique which allows local application of drugs to the regenerating rat sciatic nerve for several days is presented. The sciatic nerve was transected at the knee level and a crush lesion was made proximal to the transection. The crush lesion and the nerve segment distal to it was enclosed in a chamber made of silicone tubing (STC). The STC was perfused via a catheter connected to a miniosmotic pump. Regeneration was evaluated with the 'pinch-test' at 3, 4 and 6 days after the enclosure of the nerve. The rate of regeneration in the STC-surrounded nerve segment was 3.5 mm/day after an initial delay of 1.6 days which are values similar to those in uncovered nerves with crush lesions. Perfusion of the STC with either vinblastine, cycloheximide, actinomycin D or mitomycin C inhibited regeneration. The effects were confined to the STC-covered region. Leakage of drugs was too small to affect the nerve outside the chamber. The results suggest that regeneration requires proliferation and protein synthesis in the cells surrounding the growing axons. This technique could be useful for studies of the local effects of various drugs, specific antibodies, potential growth factors etc. on regeneration of peripheral nerves.

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Axonal growth in mesothelial chambers: effects of a proximal preconditioning lesion and/or predegeneration of the distal nerve stump.

Preformed, autologous mesothelial chambers were utilized to study axonal growth following selective predegeneration of the distal nerve stump and/or preconditioning of the proximal nerve stump. The left and/or right sciatic nerve of rats was exposed and transected in the thigh. Two weeks after transection, the left proximal nerve stump was cross-anastomosed with the right distal nerve stump by using a mesothelial chamber leaving a 15-mm gap between the two nerve stumps. Previous studies have shown that axonal overgrowth normally does not occur over this gap distance to the distal stump. Three months after cross-anastomosing, regeneration across the 15-mm gap was evaluated by muscle action potential recordings and light microscopical examination. In experiments in which a distal nerve stump was selectively degenerated and the proximal segment was freshly cut, axons had bridged the 15-mm gap in six of seven rats. When a proximal preconditioned nerve stump was matched with a freshly cut distal stump, axonal overgrowth occurred in only 4 of 10 experiments. In experiments including a proximal preconditioned nerve stump and a distal predegenerated stump, axons bridged the gap in 6 of 8 experiments. We concluded that a priming lesion, including manipulation with proximal and/or distal stump, enhances axonal growth in mesothelial chambers.

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Transient increase in insulin-like growth factor I immunoreactivity in rat peripheral nerves exposed to vibrations.

Hind legs of adult rats were exposed to vibrations (81 Hz; amplitude 0.50 mm peak to peak) for 4 h during two consecutive days. The sciatic, tibial and plantar nerves were isolated and processed for immunohistochemical demonstration of IGF-I (insulin-like growth factor I; somatomedin C) immunoreactivity at different time intervals after the vibration exposure. In sham-exposed rats the axons in peripheral nerves showed no or faint IGF-I immunoreactivity while most Schwann cells were negative. Exposure of the hind legs to vibrations induced increased IGF-I immunoreactivity in the Schwann cells, demonstrable at the end of the exposure period and reaching maximal intensity 2-3 days after vibration exposure. Several distended axons similarly showed increased staining. The IGF-I immunoreactivity decreased after 7-10 days to almost the level in the control nerves. The most extensive changes were observed in the plantar nerves. The tibial nerves similarly expressed strongly increased IGF-I immunoreactivity in their Schwann cells. The sciatic nerve showed, however, only slightly to moderately increased staining. Cells in the epineurium of the plantar and, to a limited extent, of the tibial nerves expressed concomitantly increased IGF-I immunoreactivity. We conclude that the transiently increased IGF-I immunoreactivity in peripheral nerves reflects reactive changes caused by vibrations and most prominently expressed by the Schwann cells.

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Neurotropism in nerve regeneration: an immunohistochemical study.

A rectangular pseudomesothelial-lined chamber was used to elucidate the hypothesis that in adult rats neurotrophic factors are formed after nerve injury and may influence regeneration of peripheral nerves. The proximal end of a cut sciatic nerve was inserted into one corner of the chamber. In one group of animals the distal end of the cut sciatic nerve was implanted in the diagonally opposite corner of the chamber. In another group we just introduced the proximal end of the sciatic nerve; no distal implant was used. The organization, length and direction of the nerve fibres, regenerating from the proximal end of the sciatic nerve, was visualized immunohistochemically with the aid of antibodies against neurofilaments at 2, 3 and 4 weeks after surgery. When a distal sciatic nerve segment was used, nerve fibres regenerating from the proximal cut end of the sciatic nerve showed an organized growth across the chamber, formed bundles and grew into the diagonally implanted nerve piece. If there was no distal implant, the growth of the randomly directed nerve fibres ceased after about two weeks, resulting in formation of a neuroma-like structure. Increased immunoreactivity of the trophic peptide insulin-like growth factor I (IGF-I, somatomedin C) was demonstrated in the regenerating nerve, most evidently in reactive Schwann cells. It is concluded that a positive neurotropic effect is exerted on growing nerve fibres by injured, reactive peripheral nerve tissue. There could tentatively be a relation between nerve regeneration and local formation of trophic factors.

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Transiently increased insulin-like growth factor I immunoreactivity in tendons after vibration trauma. An immunohistochemical study on rats.

The hind limbs of anaesthetized rats were exposed to vibration trauma (81 Hz; amplitude peak to peak 0.50 mm) for 4 hours during 2 consecutive days. The animals were examined in groups of 4 immediately after the last exposure, and after 1, 2, 3, 5, 7, 10, 14 and 28 days. The Achilles tendons and the tendons of the anterior tibialis muscles were sampled and processed to demonstrate IGF-I immunoreactivity. In the normal Achilles tendon and in the tendon of the anterior tibial muscle, slight IGF-I immunoreactivity was seen in many of the long slender fibroblasts between the collagen bundles. A strong increase in the IGF-I immunoreactivity appeared in the anterior tibialis muscle tendon 3 days after the last vibration exposure. In addition, the tendon fibroblasts became hypertrophic. A similar but less striking increase in IGF-I immunoreactivity appeared in the Achilles tendon. The peak intensity and frequency of stained cells were achieved after 7 days for both tendons. The intensity then levelled off, and was normalized after 28 days. It is concluded that acute exposure to vibrations induces reactive changes in fibroblasts in tendons, which may reflect a change to a more active synthesising state, as a response to the vibration trauma. The transiently altered expression of IGF-I immunoreactivity forms a link in a chain of events regulating the functional activity level of fibroblasts in response to a trauma.

Achilles Tendon↗

Peripheral nerve regeneration in Gore-tex chambers.

Gore-tex chambers were used to bridge a 6 mm gap between the proximal and distal nerve stumps of a rat sciatic nerve. The wall structure of these chambers is characterized by "nodes" interconnected by smaller fibrils. Chambers with internodal distances of 5, 10 and 30 microns were used. Some 30 microns chambers were coated from the outside with Gore-tex (0.2 micron internodal distance) and others were coated from the inside. Regeneration after 12 weeks, as evidenced by muscle action potential recordings and light microscopy, was successful regardless of what type of chamber had been used. The organization of the nerve structure varied among different chamber types. A well organized coaxial nerve structure with myelinated axons was observed if inner-coated chambers were used. In chambers that were not coated or in outer-coated chambers tissue completely filled the chambers, and myelinated axons were arranged in mini-fascicles surrounded by loose connective tissue.

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