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L B Dahlin

Publications and source records attributed to L B Dahlin.

88 records · Page 5Linked to original sources

Effects of epidural and intrathecal application of collagenase in the lumbar spine: an experimental study in rabbits.

An experimental model is described in which collagenase in different concentrations and volumes were applied epidurally or intrathecally in the rabbit lumbar spine. This made it possible to study the tissue effects in a situation similar to that of collagenase leaking from a disc or accidental epidural or intrathecal injection at chemonucleolysis. Epidurally applied collagenase, in higher concentration, caused a local thinning of the dura. This effect was reduced at lower concentrations and volumes. Intrathecally injected collagenase, even in small amounts, caused intrathecal hemorrhage and acute paraplegia in the hind limbs. Therefore, in the clinical situation, intrathecal injection of collagenase must be avoided.

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Intraneural edema following exposure to vibration.

Peripheral neuropathy represents a well-known complication from long-term exposure to vibration. In the present study an experimental model is presented with the purpose of analyzing the formation of intraneural edema following vibration exposure. Vibration (82 Hz, peak-to-peak amplitude 0.21 mm) was induced in the hind limb of rats by the use of vibrating electric motors during 4 h/d for 5 d. Tracer techniques (with albumin Evans blue and horseradish peroxidase) were used to study the permeability of intraneural microvessels after the vibration exposure on day 5. It was found that the vibration trauma in this model induced epineurial edema in the sciatic nerve. It is hypothesized that the formation of intraneural edema may be an important pathophysiological factor in the occurrence of vibration-induced neuropathy.

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Effects of nerve compression on fast axonal transport in streptozotocin-induced diabetes mellitus. An experimental study in the sciatic nerve of rats.

The hypothesis that nerves in diabetes mellitus exhibit an increased susceptibility to compression was experimentally tested. Inhibition of fast axonal transport was induced by local compression in sciatic nerves of rats with streptozotocin-induced diabetes mellitus. Fast anterograde axonal transport was measured after application of 3H-leucine to the motor neurone cell bodies in the spinal cord. The sciatic nerve was subjected to local, graded compression in vivo by a small compression chamber. The amount of accumulation of proteins was quantified by calculation of a transport block ratio. Compression at 30 mm Hg for 3 h induced a significantly greater (p less than 0.05) accumulation of axonally transported proteins at the site of compression in nerves of diabetic animals (transport block ratio: 1.01 +/- 0.35; n = 7) than in nerves of controls (0.67 +/- 0.16; n = 7). Accumulation was significantly higher in ligature experiments of both control (1.34 +/- 0.44; n = 8; p less than 0.01) and diabetic animals (1.45 +/- 0.30; n = 8; p less than 0.05), indicating that the block of transport in compressed nerves was incomplete. Neither sham compressed diabetic (0.50 +/- 0.09; n = 6) nor control (0.49 +/- 0.11; n = 6) nerves showed any block of axonal transport. The possible causes of the increased inhibition of fast axonal transport in diabetic rats are discussed. The results indicate that diabetes may lead to an increased susceptibility of peripheral nerves to compression.

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Experimental hyperthyroidism stimulates axonal growth in mesothelial chambers.

An experimental model is presented for studying axonal growth after experimental hyperthyroidism and hypothyroidism. The left sciatic nerve of the rat was transected and transposed to the back. The proximal nerve stump was inserted into a 50-mm-long mesothelial chamber leaving the distal end of the chamber open. Different groups of young adult rats were given daily injections of thyroxine (10 micrograms/100 g body weight) or the goitrogen, thiamazol, in the drinking water (0.125 g/liter) for 12 weeks. Thyroxine treatment increased significantly the extent of axonal outgrowth from the proximal nerve stump compared with untreated rats. Experimental hypothyroidism (thiamazol treatment), evidenced by a retarded body growth, did not affect the extent of axonal outgrowth. In other experiments the left proximal nerve stump was cross-anastomosed with the right distal nerve stump. The two nerve stumps were bridged with a mesothelial chamber leaving a 15-mm gap. This gap distance is known from our previous studies to inhibit axonal overgrowth to the distal nerve stump. As evidenced by histological evaluation, in three of six thyroxine-treated rats, axons had bridged the 15-mm gap. We conclude that experimentally induced hyperthyroidism enhances axonal growth in mesothelial chambers.

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Effects of graded experimental compression on slow and fast axonal transport in rabbit vagus nerve.

Effects of compression at low pressures on slow and fast axonal transport was investigated in rabbit vagus nerve. Proteins in the sensory fibres were radiolabelled by injection of [3H]leucine or [35S]methionine into the nodose ganglion. A small compression chamber and/or ligatures were applied around the cervical part of the vagus nerve for 8 h, at an appropriate time for the subsequent analysis of the effects of compression on both slow and fast transport of radiolabelled proteins. In normal nerves there were two waves of slowly transported proteins with rates of about 12-15 and 25-30 mm/day, respectively. SDS-polyacrylamide gel electrophoresis was used and confirmed that the main proteins which accumulated proximal to the ligatures had a molecular weight of 54 000-56 000. Neither compression of the nerve at 20 mm Hg nor sham-compression induced any statistically significant accumulation of slowly transported proteins at the site of compression. A higher pressure, i.e. 30 mm Hg, induced a marked but incomplete accumulation of slowly transported proteins. Fast transport was partially inhibited in some, but not all, nerves, when 20 mm Hg was applied for 8 h, in contrast to the lack of effect found previously with the same pressure applied for only 2 h. Despite these slight differences, the results indicate that both slow and fast transport are impaired by low pressure levels of around 20-30 mm Hg, which are comparable with those found in human compression neuropathies. The impaired provision of cytoskeletal elements to the distal axon may be of significance in the pathophysiology of nerve entrapment syndromes.

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Graded inhibition of retrograde axonal transport by compression of rabbit vagus nerve.

Effects of experimental compression at different pressures on retrograde axonal transport were studied in rabbit vagus nerve. Proteins in the sensory neurones were radiolabelled by injection of [3H]leucine into the nodose ganglion. Sixteen hours after labelling, a small compression chamber and/or ligatures were applied around the cervical part of the vagus nerve for 8 h. Compression of the vagus nerve at 20, 30 and 200 mm Hg pressure induced a graded inhibition of both retrograde and anterograde transport of the radiolabelled proteins. Neither retrograde nor anterograde transport was affected by the presence of the non-inflated chamber. The results indicate that compression at pressures similar to those found in human carpal tunnel syndrome can block retrograde axonal transport. The consequences of inhibition of retrograde and anterograde axonal transport for the metabolism in the nerve cell bodies are discussed.

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Absence of ongoing activity in fibres arising from proximal nerve ends regenerating into mesothelial chambers.

Morphological studies have indicated that proximal nerve ends of transected rat sciatic nerves regenerating into preformed mesothelial chambers show a different organization as compared to neuromas developed in contact with a muscle fascia. We have studied the physiological properties of nerve fibres arising from these types of preparations with reference to ongoing activity, response to mechanical stimulation and noradrenaline sensitivity. The study included also fibres arising from ligated and encapsulated neuromas. Fibres with ongoing activity arising from the neuroma could be found from neuromas in contact with a muscle fascia and also from ligated and encapsulated neuromas. This ongoing activity was enhanced by mechanical stimulation and i.v. infusion of noradrenaline. In contrast, fibres arising from proximal nerve ends in mesothelial chambers did not show ongoing activity. These silent fibres responded dynamically to light mechanical stimulation. Noradrenaline did not induce ongoing activity in these fibres.

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Evidence indicating trophic importance of IGF-I in regenerating peripheral nerves.

The mechanisms influencing regeneration of peripheral nerves are incompletely known, but growth factors are supposed to play a key role. In the present study, we demonstrate, with the aid of immunohistochemical methods, that somatomedin C (Sm-C/insulin-like growth factor I/IGF-I) rapidly increased from low to high concentrations, reaching peak values in 2 weeks, in regenerating sciatic nerves of adult rats. In addition, IGF-I was demonstrated extracellularly, never observed in the control nerves. Reactive Schwann cells appeared to be the major source for IGF-synthesis. Higher concentrations were seen in tubulated nerves as compared to sutured ones. It is proposed that IGF-I exerts important growth supporting effects on regenerating peripheral nerves.

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Mechanical effects of compression of peripheral nerves.

Effects of graded compression on nerve function were analyzed in order to evaluate the relative importance of pressure level and duration of compression for functional deterioration. The pressure was applied by means of a small inflatable cuff. The effects of two pressure levels, i.e., 80 mm Hg applied for 2 hr or 400 mm Hg applied for 15 min, were studied in rabbit tibial nerves. The lower pressure tested, which is known to induce ischemia of the compressed nerve segment, also causes some degree of mechanical deformation of the nerve trunk, which leads to incomplete recovery following pressure release. The duration of compression is of importance for the degree of nerve injury even at the higher pressure level tested.

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Tissue specificity in nerve regeneration.

In 1944 Weiss & Taylor presented experimental evidence against "neurotropism" in nerve regeneration. We used a silicone Y-chamber system to repeat some of those experiments. The proximal stump of transected rat sciatic nerve was introduced into the proximal inlet of the Y. One of the distal outlets was left empty, plugged or occupied by a tendon graft, the other outlet being occupied by a nerve graft. Analysis after 4 and 12 weeks showed in all cases a preferential or exclusive axonal growth towards the nerve piece. The results, indicating the existence of "tissue specificity", are contradictory to the results reported by Weiss & Taylor (30). The findings are discussed with respect to possible influence of humoral, cellular and molecular factors associated with the distal nerve stump as well as the matrix, formed between both nerve segments.

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Changes in fast axonal transport during experimental nerve compression at low pressures.

The minimal pressure for impairment of fast anterograde axonal transport was determined in rabbit vagus nerve. Proteins, transported by fast anterograde axonal transport, were labeled by a microinjection of [3H]leucine into the nodose ganglion, and a small compression chamber was applied around the cervical vagus nerve. In this way the nerve was subjected to acute, graded compression. Compression at 20 mm Hg for 2 h as well as sham compression did not induce accumulation of axonally transported proteins at the level of compression. However, a pressure of 30 mm Hg for 2 h induced a block of axonal transport at the site of compression. The causes of the axonal transport block are discussed as well as the minimal pressure level in relation to pressures found in clinical nerve compression lesions.

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Axonal growth in mesothelial chambers. The role of the distal nerve segment.

An experimental model is presented for studying nerve regeneration over gaps of various lengths between the both ends of a severed nerve. After transferring left and right sciatic nerves of rat to the back, the gap between the two nerve ends could be bridged by a preformed, tube-shaped mesothelial chamber of a desired length. When the gap length was 10 mm or less, a well developed nerve structure was generated in the chamber between the nerve ends, and axons from the left sciatic nerve reinnervated muscles in the right limb via the right sciatic nerve. When the gap length was extended to 15 mm or more no such regeneration occurred. When no distal nerve end was introduced into the chamber, there was a limited growth into this chamber over only 5-6 mm. This "limited growth phenomenon" is discussed with respect to a lack of "trophic" or cellular support from a distal nerve segment. It is also proposed that the termination of growth, seen under these circumstances, may suggest a new principle for avoiding the development of neuromas after nerve transections.

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Nerve regeneration across an extended gap: a neurobiological view of nerve repair and the possible involvement of neuronotrophic factors.

We have compared the anatomic and functional regeneration of a transected sciatic nerve following regrowth from its proximal stump through either preformed empty mesothelial chambers or autologous nerve grafts bridging a 10 mm gap. Within the mesothelial chambers an organized multifascicular nerve trunk forms between the proximal and distal stumps. After 3 months, distal segment cross sections from the mesothelial chamber and nerve graft groups did not differ with respect to axonal density or distribution of axonal diameters. Mean conduction velocities across the gaps were also similar, although the nerve graft group had a wider distribution of velocities. Little or no regeneration was evident when the gap between the nerve stumps was left empty. These results suggest that if the regrowing proximal stump is in an appropriate environment, it can form a well organized and oriented nerve trunk. In the mesothelial chambers, the regenerating nerve is surrounded by a loose cellular stroma and a small amount of interstitial fluid, which was found to contain trophic activity for cultured rodent sensory neurons. Such factors may also support nerve regeneration in vivo.

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Reorganization and orientation of regenerating nerve fibres, perineurium, and epineurium in preformed mesothelial tubes - an experimental study on the sciatic nerve of rats.

Regeneration of severed peripheral nerves is unfortunately often incomplete, due to loss of nerve fibers and neuroma formation. A new approach is presented with the intention of improving the conditions for nerve repair. In the first of the two stages, a pseudosynovial tube is formed around a silicone rubber rod, surrounded by a stainless steel spiral, which was placed in the backs of rats. This tube, in the second stage, is used as a free "tube graft" to bridge gaps of about 10-12 mm lengths in the severed sciatic nerve. The tube was kept open by the metal spiral. Regenerating nerve fibers with their sprouts grew into the initially open space in the tube. A new nerve trunk was formed, comprised of closely packed myelinated and unmyelinated axons, organized into fascicles. Demonstration by electron microscopy and by EMG recording of reinnervation of foot muscles supported successful long-term results. The fascicles were delimited by perineurial and epineurial sheaths and, furthermore, showed signs of maturation. It was also demonstrated that the nerve-fiber regeneration ceased after a few weeks if there was no distal nerve inserted into the tube. The importance of optimizing the interaction between local factors and regenerating nerve fibers for reestablishment of functionally valuable motor units is discussed.

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Addition of cultured Schwann cells to tendon autografts and freeze-thawed muscle grafts improves peripheral nerve regeneration.

The effects of addition of Schwann cells on peripheral nerve regeneration through a novel graft material-the tendon autograft-and a conventional freeze-thawed muscle graft, were studied in the rat sciatic nerve. Adult Schwann cell cultures were established from predegenerated nerves. The Schwann cells were added to the autologous grafts by coculture (tendon autograft) or injection (freeze-thawed muscle graft). Both graft types supported adherence of the added Schwann cells. Addition of cultured Schwann cells to the two different graft models improved regeneration by increasing the rate of axonal outgrowth as compared with similar grafts without added cells.

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