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Biomedical subjects

M Kanje

Publications and source records attributed to M Kanje.

At least 73 records · Page 4Linked to original sources
PubMed1990

Effects of repetitive conditioning crush lesions on regeneration of the rat sciatic nerve.

The effect of repetitive conditioning lesions was tested on regeneration of the rat sciatic nerve. The nerve was conditioned by crush lesions one, two or three times with an interval of 2 or 4 days between each successive lesion. Axonal elongation was measured 3 days after a final test crush lesion. Two conditioning lesions stimulated axonal elongation more than one, while a third conditioning lesion had no further effect on axonal outgrowth. However, if the number of conditioning lesions were varied within a constant conditioning interval, outgrowth after the test lesion was the same. This suggests that the conditioning interval and not the number of conditioning lesions determined the outgrowth after a test lesion. When the conditioning lesion(s) and the test lesion were made at the same place, outgrowth was longer than if the lesions were spatially separated. Incorporation of [3H]thymidine in the regenerated nerve segment showed that proliferation of non-neuronal cells was initiated by each lesion. By counting the number of cell nuclei this proliferation was shown to correspond to an increase of cells in the regenerating nerve. It is therefore possible that the greater number of non-neuronal cells in the distal nerve segment accounts for the enhanced conditioning lesion effect in nerves where the conditioning and test lesions are made at the same place.

Animals↗
PubMed1990

The initial period of peripheral nerve regeneration and the importance of the local environment for the conditioning lesion effect.

The aim of this study was to investigate the early period of neurite outgrowth in the regenerating rat sciatic nerve and to determine if the non-neuronal cells were important for the conditioning lesion effect. Regeneration distance was evaluated with the pinch-reflex test 6 h to 5 days after a test crush lesion. The regeneration velocity accelerated during approximately 3 days, whereupon outgrowth continued with a constant velocity. In unconditioned nerves the initial delay was 2.8 h and the constant rate of regeneration was 3.2 mm/day. In nerves with a distal conditioning lesion the initial delay was 2.4 h and the rate of regeneration increased by 52%. When the test crush was applied at the same place as the conditioning crush the initial delay was 1.9 h and the rate of regeneration increased by 61%. The conditioning lesion effect was not influenced by the distance between the cell body and the conditioning crush lesion. Furthermore, the conditioning lesion effect could not be expressed if conditioned axons grew into a freeze injured nerve section. Incorporation of [3H]thymidine increased in the regenerating nerve segment. The increase occurred earlier if this segment had been subjected to a conditioning crush lesion. The results of these experiments showed that peripheral neurites start to regenerate within a few hours after an injury, suggesting that growth cone formation is independent of the cell body reaction. A conditioning crush lesion increases the regeneration velocity and its acceleration, and the conditioning lesion effect cannot be expressed in the absence of living Schwann and other non-neuronal cells.

Animals↗
PubMed1990

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.

Animals↗
PubMed1990

Anabolic and tissue repair functions of recombinant insulin-like growth factor I.

Recombinant human insulin-like growth factor I (rhIGF-I) has been produced in yeast and purified using conventional biochemical techniques. It has been shown to have receptor-binding properties and in vitro growth-promoting activities comparable to those of plasma-derived IGF-I. The anabolic actions of IGF-I can be studied using both systemic and local administration in vivo. The growth-promoting activity and systemic anabolic actions of recombinant IGF-I were studied in mutant dwarf rats. IGF-I was infused intravenously for 9 days and resulted in a significant gain in body weight and significant bone growth, though the effects were not as great as those observed with human growth hormone (hGH). IGF-I also had selective effects on specific organs which were not observed in hGH-treated animals. The results indicate that the growth-promoting effects of IGF-I show a different pattern compared to hGH. The effects of local administration of recombinant IGF-I on tissue regeneration and maintenance were also studied in hypophysectomized and normal rats. After hypophysectomy, the regeneration processes were impaired when both peripheral nerve regeneration and incision wound healing were considered. The results indicate that local administration could have significant effects on regeneration of, for example, peripheral nerves.

Animals↗
PubMed1989

Nerve regeneration and serum levels of insulin-like growth factor-I in rats with streptozotocin-induced insulin deficiency.

Peripheral nerve regeneration was studied in female Sprague-Dawley rats with streptozotocin-induced insulin deficiency. Nerve regeneration was provoked by a crush lesion on the sciatic nerve 21 days after the streptozotocin injection. The regeneration was assessed by a pinch test at different time-points after injury. The rate of regeneration in insulin-deficient animals, 2.5 mm/day, was significantly lower than in control animals, 2.9 mm/day (P less than 0.05). There was no difference in the initial delay, i.e. the period before regeneration attains a constant velocity. One group of insulin-deficient rats was treated with insulin during the regeneration period by means of implanted osmotic mini-pumps. This treatment prevented the decrease in regeneration. After 6 days the sciatic nerves of insulin-deficient rats had regenerated 12.3 +/- 0.3 mm (mean +/- S.E.M.), while the corresponding value for insulin-treated rats was 15.7 +/- 0.6 mm. (P less than 0.01). The streptozotocin-treated rats were found to have a 39% reduction in the serum level of insulin-like growth factor-I (IGF-I) compared to control rats (0.33 +/- 0.02 micrograms/ml and 0.54 +/- 0.02 micrograms/ml respectively, P less than 0.001). Insulin treatment during the regeneration period completely restored the IGF-I level back to normal.

Animals↗
PubMed1989

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.

Animals↗
PubMed1989

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.

Animals↗
PubMed1989

Insulin-like growth factor (IGF-1) as a stimulator of regeneration in the freeze-injured rat sciatic nerve.

The effect of insulin-like growth factor (IGF-1) on the ability of the rat sciatic nerve to regenerate into a freeze-injured nerve segment was investigated. The freeze-injured segment was perfused for 6 days with Ringer solution and different concentrations of IGF-1, dispensed by a subcutaneously implanted osmotic minipump. At a pump concentration of 50, 100 and 200 micrograms IGF-1/ml the regeneration length increased with 14, 25 and 26%, respectively, as measured by the pinch test and by immunocytochemical staining for neurofilaments (NF) in the growing neurites. Schwann cells invading the freeze-injured segment were visualized by immunostaining for S-100 protein. In nerves perfused with Ringer solution alone the Schwann cells were present as far as the neurites had regenerated, while neurites seemed to grow slightly ahead of the Schwann cells in the nerves perfused with IGF-1. Incorporation of [3H]thymidine increased in IGF-1-treated nerves. However, IGF-1 perfusion did not increase thymidine incorporation when outgrowth of neurites was detained by a transection proximal to the freeze-injured area. The results suggest that IGF-1 affects regeneration by local stimulation of the growing neurites and that IGF-1 stimulates the proliferation of non-neuronal cells indirectly.

Animals↗
PubMed1989

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.

Animals↗
PubMed1988

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).

Animals↗
PubMed1988

Regeneration in vitro of the adult frog sciatic nerve.

The sensory axons of the adult frog sciatic nerve were found to regenerate from a local test crush in vitro, providing the nerve was subjected to a conditioning lesion in vivo 10-17 days earlier. If the latter was applied distal to the test lesion, the regeneration rate was 1.1 mm/day or only somewhat slower than in vivo. The elongation rate in vitro was maintained at an unchanged rate for at least 9 days. With the use of a two-chambered culture system we could show that the growth was dependent on local protein synthesis. If the conditioning and test lesions were both applied at the same site, the outgrowth distance after 5 days was significantly longer than when the lesions were separated and also longer than the regeneration distance 5 days after a single test lesion in vivo. The results show that the growth process is influenced by local factors and can be maintained in vitro in the absence of blood-borne signals. The present system opens unique possibilities for exploring the role of potential growth factors and other conditions involved in axonal regeneration in an adult vertebrate peripheral nerve.

Animals↗
PubMed1988

Influence of non-neuronal cells on regeneration of the rat sciatic nerve.

The ability of the rat sciatic nerve to regenerate into a previously frozen distal nerve segment was studied and compared to regeneration after a crush lesion. The regeneration rate in the frozen segment was 1.9 mm/day, which was approximately half of that observed after a crush lesion (3.3 mm/day). If an unfrozen nerve segment was left intact beyond the frozen section, the rate of regeneration increased to 3.2 mm/day. However, a fresh nerve segment sutured along the frozen segment did not significantly affect the rate of regeneration. Incorporation of [3H]thymidine in the regenerating nerve, analyzed after 1, 3 and 6 days, showed an increased labelling in the frozen segment. This increase spread from the proximal nerve segment into the frozen section. In nerves where a segment was left intact beyond the frozen section, [3H]thymidine incorporation was seen to enter the frozen section from both sides. The spreading of [3H]thymidine incorporation appeared to correlate with the rate of regeneration. However, the same pattern of incorporation could be observed in nerves where regeneration was detained by a transection. The results suggest that Schwann and/or other cells which invade the frozen nerve segment affect the rate of axonal elongation, and that the migration of these cells occurs independently of regenerating fibers.

Animals↗
PubMed1988

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.

Animals↗
PubMed1988

Orthograde and retrograde axonal transport in the regenerating frog sciatic nerve show different sensitivities to vanadate.

The outgrowth region of the regenerating frog sciatic nerve shows an increased permeability for various drugs. The present experiments indicate that this is also true for vanadate, a substance of special interest in relation to axonal transport. Six days after a bilateral crush lesion, the sciatic nerves, including the spinal ganglia, were incubated in a compartmented chamber. Orthograde transport was assessed from the distribution and the accumulation of [3H]leucine-labelled proteins in the nerve growth region. Retrograde transport was examined by allowing orthogradely transported labelled materials to reverse at the regenerating region and then to accumulate at a ligature during a second incubation period. Vanadate at 0.5 mM and higher concentrations was found to inhibit orthograde and retrograde transport in the outgrowth region (6 mm long at 6 d after crush), whereas 0.2 mM vanadate inhibited transport only in the retrograde direction. The observations lend further support to the idea that the mechanisms of transport in the two directions are different.

Animals↗
PubMed1987

Incorporation of [32P]phosphate into nucleotides of the dorsal root ganglia of regenerating rat sciatic nerve.

[32P]Phosphate incorporation into nucleotides of the dorsal root ganglia (DRG) was studied after a crush lesion of the rat sciatic nerve. DRG were labelled during a 2-h, in vitro incubation in a balanced salt solution containing [32P]orthophosphate, 1, 2, 4 and 8 days after the crush lesion. Nucleotides were analyzed by HPLC on an ion-exchange column. An increased incorporation of 32P was found in DRG of the injured nerve for all the studied time periods. This increase was unevenly distributed among the nucleotides. UTP, CTP and ADP showed the largest and most persistent increases in labelling. The specific activity of 4 analyzed nucleotides (ATP, ADP, UTP and CDP) remained constant in DRG from crushed nerves. Thus, the observed increase in 32P-labelling could not solely be due to an increased uptake of label but must also reflect an enhanced metabolism of nucleotides in regenerating DRG. The finding that alterations of nucleotide metabolism could be observed within one day after the crush lesion suggests that this response can be used as a valuable tool for studies of the initial events of regeneration.

Animals↗
PubMed1987

The use of the regenerating frog sciatic nerve for pharmacological studies of orthograde and retrograde axonal transport.

The outgrowth region of the regenerating frog sciatic nerve shows an increased permeability for various drugs, which has been utilized for pharmacological studies of axonal transport. Six days after a bilateral crush lesion, the nerves, including the spinal ganglia, were incubated in a compartmented chamber. Orthograde transport was assessed from the proximodistal distribution and the accumulation of labelled proteins in the nerve growth region. Retrograde transport was examined by allowing orthogradely transported materials to reverse at the regenerating region and then to accumulate at a ligature during a second incubation period. The distribution of radioactivity along the nerve was assayed by fluorography of whole-mount nerve preparations or by scintillation counting. Fluorography made it possible to increase the spatial resolution and to demonstrate effects in the elongating part of the regenerating nerve. Colchicine at low concentrations (10-100 microM) only inhibited axonal transport in the outgrowth region (6 mm long at 6 days after crush) and along some mm of the nerve proximal to the crush. Compound 48/80 (50 micrograms/ml), the most specific calmodulin inhibitor so far described, inhibited the transport along the same part of the nerve. Cytochalasin B (10 micrograms/ml) inhibited transport by effects limited to the outgrowth region. Both orthograde and retrograde transport showed sensitivity to these and some other drugs. The regenerating frog sciatic nerve seems to have significant advantages for pharmacological studies of axonal transport.

Animals↗
PubMed1987

The effects of trifluoperazine on fast and slow axonal transport in the rabbit vagus nerve.

The effects of trifluoperazine (TFP) on fast and slow axonal transport (AXT) of labeled proteins were examined in the rabbit vagus nerve. Cuffs soaked in a 10 mM, but not 0.1 mM or 1 mM, concentration of TFP applied locally around the vagus nerve in vivo blocked both fast and slow AXT, as measured by the accumulation of 3H-labeled proteins. In vitro, fast AXT was affected by 0.1 mM TFP. The TFP cuff treatment caused a reduction in the number of axonal microtubules (MT) whereas cuffs soaked in saline had no effect. The levels of ATP, ADP, and AMP were not significantly lowered by the TFP treatment. The results suggest that both fast and slow AXT are sensitive to TFP treatment, and that the axonal MT-system may be the main target of the drug.

Adenine Nucleotides↗