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Biomedical subjects

G Lundborg

Publications and source records attributed to G Lundborg.

At least 73 records · Page 4Linked to original sources

Regeneration of axons from central neurons into microchips at the level of the spinal cord.

Axons from central neurons can regenerate into the tissue matrix formed within a silicone tube capped with two pieces of peripheral nerve, one of which had been sutured to a lesion in the spinal cord. Such axons can grow through a transversely positioned microchip in the tube. These observations suggest that it is feasible to establish functional contact between external electronic equipment and regenerating central nervous axons making it possible to monitor and control their electrical activity. The findings open new perspectives for restoration of motor and sensory functions following spinal cord lesions.

Animals↗

Selective inhibition of early axonal regeneration by myelin-associated glycoprotein.

When the distal stump of a transected peripheral nerve is brought into the vicinity of the proximal nerve stump, the regenerating axons advance toward it across the gap. Similar results are obtained when a predegenerated nerve segment is used. However, when a nerve segment subjected to proximal axotomy 7 days earlier (7-day nerve segment) was placed close to the proximal end of a freshly cut nerve at a distance of less than 1.5 mm, there were neither regenerating axons nor sprouts. The same inhibition of axonal regeneration was also exhibited when a nerve segment subjected to axotomy 9 to 14 days earlier was used. To examine the inhibitory effect of the nerve segments on established regenerating axons, we positioned a 7-day nerve segment in close apposition to a proximal nerve end at 2 or 3 days after transection. The growth of the 3-day-old regenerating axons, already ensheathed by Schwann cells, was not disturbed, but the 2-day-old regenerating axons, consisting of naked axons, were eliminated by the 7-day nerve segment. It is assumed that the findings reflect a mechanism serving to eliminate abundant sprouts and immature axons, probably conferring optimum regeneration and maturation of outgrowing pioneer axons. The inhibitory effect on abundant sprouts and immature axons was completely blocked by local application of antibodies to myelin-associated glycoprotein (MAG). The MAG-containing cells appeared at 6 to 12 days after axotomy.

Animals↗

Artificial sensibility based on the use of piezoresistive sensors. Preliminary observations.

Piezoresistive sensors, applied to the fingertips of non-sensate fingers, were used for the detection of touch and pressure in four patients with recent median nerve repairs, and in one patient using a myoelectric prosthesis. The signals from the sensors, produced by the tactile stimuli, were processed and transposed as electrical stimuli to sensate skin of the ipsi- or contralateral arm by the use of skin electrodes. With this setup the test subjects could rapidly learn to differentiate between tactile stimuli applied to different fingers, thereby regaining spatial resolution in the hand. All five patients rapidly improved their ability to regulate the power of pinch grip without the help of vision. The patient with a hand prosthesis rapidly learned to discriminate between four different levels of pressure, applied to the thumb by four different Semmes--Weinstein monofilaments (75, 125, 280 and 450 g). These results indicate that the system is of potential value for patients lacking sensibility or using prostheses.

Adult↗

Vibrotactile sense in the hand-arm vibration syndrome.

OBJECTIVES: The purpose of this study was to investigate disturbances of the vibrotactile sense and their relation to clinical symptoms and findings among male symptomatic workers suffering from the hand-arm vibration syndrome. METHODS: Ninety-six such patients were interviewed and given a clinical and tactilometric examination. The symptoms were classified according to the Stockholm Workshop Scale. A sensibility index was used to quantify vibrotactile sense in the tactilogram. RESULTS: An abnormal sensibility index (<0.8) was recorded for 57.3% of the patients (mean of 4 fingers), at least 1 finger being abnormal in 72.9% of the patients. The sensibility index did not statistically differ between the patients suffering from sensorineural symptoms and those with vibration white finger. The stages of sensorineural symptoms, according to the Stockholm Workshop Scale, corresponded with the sensibility index, whereas the stages of vibration white finger did not. There were significant differences in the sensibility index between the fingers, between the right and left hands, and between the fingers innervated by the ulnar and median nerves. Bilateral symptoms and cold intolerance were associated with considerable impairment of the vibrotactile sense. Clinical median nerve involvement in the carpal tunnel was not reflected by the sensibility index. CONCLUSIONS: There is a considerable degree of neural involvement in all symptomatic vibration-exposed patients irrespective of symptoms. As symptoms progress, the severity of sensorineural symptoms, but not of vibration white finger, is reflected by the sensibility index. Cold intolerance is strongly related to nervous involvement and should be noted in the patient history. Tactilometry should be performed on 1 median and 1 ulnar nerve-innervated finger of both hands, as an examination of 1 finger alone may be misleading.

Adult↗

Nerve regeneration in a 'pseudo-nerve' graft created in a silicone tube.

The pseudo-nerve, which contains longitudinal Schwann cell columns without axons and surrounded by perineurium-like tissue but no axons (Q. Zhao, L.B. Dahlin, M. Kanje, G. Lundborg, Brain Res. 592 (1992) 106-114), was applied as a graft to repair nerve defect in rats. Creation of the pseudo-nerve was accomplished by inserting the proximal and distal stumps of a cut sciatic nerve into a silicone tube. The proximal insert was cut far proximally to prevent axons from entering the tube. After 4 weeks, the pseudo-nerve was harvested, trimmed into a 10-mm long graft and transplanted into a corresponding defect of the contralateral sciatic nerve. Nerve regeneration through the pseudo-nerve was examined by pinch reflex test and neurofilament staining after 6 days or by morphology after 4, 6 or 8 weeks. The results showed that the pseudo-nerve could induce nerve regeneration to a similar extend as a real nerve graft. The neurobiological composition of the pseudo-nerve and the factors influencing its formation were also studied. By double staining of S-100 and laminin we found that the longitudinally organized Schwann cell columns in the pseudo-nerve were surrounded by basal laminae and ensheathed by a layer of vascularized perineurium-like tissue. Macrophages (ED1 and ED2) and their products interleukin-1beta (IL-1beta) and transforming growth factor-beta1 (TGF-beta1) were constantly present in the pseudo-nerve. Besides, the size of tube was a crucial factor in influencing pseudo-nerve formation, e.g. a thicker pseudo-nerve was formed in tubes with larger diameters or shorter gap lengths. No pseudo-nerve was formed when the gap was 15 mm long. When both proximal and distal inserts were isolated nerve segments the pseudo-nerve was still formed but thin, probably because of compromised vascular supply. Taken together, the results suggested that the pseudo-nerve contains the essential neurobiological elements to induce successful axonal elongation.

Animals↗

Rat sciatic nerve regeneration through a micromachined silicon chip.

The capacity of regenerating nerve fibres to grow through a perforated silicon chip was tested using the silicone chamber model for nerve regeneration. The chips were fabricated as circular membranes, 4 mm in diameter, thickness 60 microns, with a perforated area, 2 mm in diameter, in the centre. Three types of chips were fabricated utilizing anisotropic etching. The chips were glued with silicone adhesive between two halves of silicone rubber tubing (total length 8 mm, inner diameter 1.8 mm, outer diameter 3.0 mm) which was used to bridge a 4 mm gap between the proximal and distal nerve stumps of a transected rat sciatic nerve. The capacity of regenerating nerve fibres to grow through the holes of the chip was analysed by light and scanning electron microscopy after 4 or 16 weeks of regeneration. Furthermore, the muscle contractility force of the gastrocnemius muscle was measured after 16 weeks of regeneration and compared as a percentage of the contralateral uninjured side. Nerves generated through chips with hole diameters of 10 or 50 microns were morphological and functional failures. The nerve structures distal to chips with hole diameters of 100 microns contained many myelinated nerve fibres in a minifascicular pattern after both 4 and 16 weeks of regeneration. The muscle contractility force was 56% of that of contralateral control muscles.

Animals↗

Anchorage of wrist joint prostheses to bone using the osseointegration principle.

Five patients with rheumatoid arthritis (age 28-60 years) underwent wrist joint arthroplasty with individually designed artificial joint mechanisms, anchored to bone using the osseointegration principle. We report on the result from a 4 to 6.5 year follow-up with special emphasis on the fixation of the prosthesis to bone. There was no bone resorption or loosening of screws. Osseointegration of the titanium screws occurred in all cases and persisted throughout the observation period, although scattered lytic zones could sometimes be seen around the screws. The clinical results were satisfactory with pain relief and maintenance of a functional range of movement. The principle has prospects for fixation of a wrist joint mechanism to bone, although the presently used joint mechanism requires further refinement.

Adult↗

Sensory function after median nerve decompression in carpal tunnel syndrome. Preoperative vs postoperative findings.

The sensory recovery was monitored for up to 1 year after decompression of the median nerve in 69 patients with carpal tunnel syndrome. Special attention was paid to the rate of recovery, the importance of constant or intermittent numbness or paraesthesiae preoperatively and the influence of gender. Most patients with numbness/paraesthesiae and those with abnormal two-point discrimination recovered within 10 days. Perception of touch and vibration recovered within 3 weeks in most patients but those with abnormal nerve conduction/sensory amplitude recovered slowly during follow-up. After 1 year patients with intermittent preoperative symptoms were significantly more likely to achieve normal nerve conduction and perception of touch. Women were more likely to achieve normal nerve conduction and perception of touch. A comparison of recovery between matched men and women with identical preoperative status showed no significant difference. The results indicate the importance of early treatment of carpal tunnel syndrome.

Adult↗

A new type of "bioartificial" nerve graft for bridging extended defects in nerves.

In the rat sciatic nerve, a gap of around 10 mm in nerve continuity seems to be the maximal distance which can be successfully repaired by silicone tubes. In this study we tested if a new artificial nerve graft, composed of eight polyamide filaments (diameter 250 microns) placed inside silicone tubes (1.8 mm inner diameter), could be used to bridge an extended gap (15 mm) in rat sciatic nerve. Silicone tubes containing eight polyamide sutures were found to support regeneration across such a gap. After 4 weeks sensory fibres had bridged the gap and grown into the distal nerve segment as revealed by a positive pinch reflex test as well as positive staining for neurofilaments in the distal nerve segment. Myelinated axons could be observed in the tissue matrix formed in between and peripheral to the synthetic filaments along the whole length of the tube. In contrast, when silicone tubes without filaments were used to bridge the 15 mm gap, the tubes contained only fluid or in two cases a thin tissue strand. No positive pinch reflex response was elicited in the nerve segment distal to such a tube. We conclude that the new artificial nerve graft can be used to support regeneration across extended gaps in nerves.

Animals↗

Tubular versus conventional repair of median and ulnar nerves in the human forearm: early results from a prospective, randomized, clinical study.

Injury to a peripheral nerve is followed by local synthesis and release of neurotrophic factors of importance for the regeneration process. This concept was adopted for repair of transected human median and ulnar nerves in the forearm. As an alternative to conventional microsurgical repair of the nerve trunk, silicone tubes of appropriate size were used to enclose the injury zone, intentionally leaving a gap measuring 3-4 mm between the nerve ends inside the tube. The early results from a prospective, randomized, clinical study comparing this principle with conventional microsurgical technique for repair of human median and ulnar nerves, is presented. Eighteen patients (14 men and 4 women), aged 12-72 (mean, 29.5) years, were randomized to either tubulization (11 cases) or conventional microsurgical repair (7 cases). A battery of tests for sensory and motor functions of the hand were carried out at regular intervals for up to 1 year after surgery. The results show no difference between the both techniques, with the exception of perception of touch, which showed a significant difference (p < .05) at the 3-month checkup in favor of the tubulization technique. At re-exploration 11 months after the initial procedure (1 case), the former gap was replaced by regenerated nerve tissue in direct continuity with the proximal and distal parts of the nerve trunk, the exact level of the former injury being impossible to identify. Study data demonstrate an intrinsic capacity of human major nerve trunks to reconstruct themselves in a preformed space when an optimal environment is offered and the surgical trauma is minimized.

Adolescent↗

Tendon repair--cellular activities in rabbit deep flexor tendons and surrounding synovial sheaths and the effects of hyaluronan: an experimental study in vivo and in vitro.

One deep flexor tendon and its surrounding sheath of each hindpaw of 48 rabbits were transected and repaired in order to investigate the abilities of rabbit flexor tendons and synovial sheaths to synthesize DNA and matrix components during healing and to study the effects of hyaluronan (HA). After repair, HA or saline was injected between the tendon and the sheath. Short-term culture and labeling in vitro were used up to 6 weeks after surgery to determine synthesis of DNA, proteoglycan, collagen, and noncollagen protein. Within tendon repair sites, the rate of cell proliferation increased and reached a maximum 5 days after surgery; within repaired synovial sheaths, the rate immediately decreased. In the healing tendons, the rate of collagen synthesis decreased and the rate of noncollagen protein synthesis remained unchanged. The opposite results were found within the healing synovial sheaths. HA did not affect the rate of cell proliferation or matrix synthesis in healing tendons or surrounding sheaths. These results show that cellular activities differ between tendons and synovial sheaths during healing and that those activities may not be affected by HA.

Animals↗

The role of macrophages in bioartificial nerve grafts based on resorbable guiding filament structures.

A 10 mm gap in a rat sciatic nerve was bridged by a bioartificial nerve graft consisting of a silicone tube containing seven longitudinally placed filaments made of non-resorbable material (polyamide [Ethilon]) or resorbable materials (polydioxanon [PDS], polyglactin [Vicryl] or catgut). The purpose was to study the tissue reaction induced by the four different types of materials. At 4 weeks an immunocytochemical technique, using ED1 and ED2 monoclonal antibodies, was used to study the presence and location of macrophages. A large number of macrophages were found accumulating on the surface of catgut and polyglactin, while few were found on the surface of polyamide and polydioxanon filaments. It is concluded that the cell layers on the filament surface mainly consisted of ED1 positive cells and their thickness depends on the filament materials.

Journal Article↗

Supersensitivity in rat micro-arteries after short-term denervation.

Contractile responses to phenylephrine and high-K+ were investigated in vitro in microvascular preparations from the rat medial plantar artery, a branch from the saphenous artery, obtained after short-term denervation in vivo. Two groups of animals were studied: (1) animals undergoing surgical resection of the saphenous nerve, and (2) animals undergoing surgical resection of both the sciatic and saphenous nerves. The animals were operated on one side only. Microvascular preparations (diameter about 325 microns) were obtained 10 days after surgery. Vessels from the non-operated side served as controls. Immunocytochemistry showed a decreased number of both neuropeptide Y (NPY) and calcitonin gene-related peptide (CGRP) immunoreactive nerve fibres in vessels after resection of the saphenous nerve only. Resection of both the saphenous and the sciatic nerve caused a complete loss of immunoreactive nerve fibres. Mechanical measurements were performed using a wire myograph. In vessels subjected to resection of the saphenous nerve the sensitivity to phenylephrine was similar to controls. Vessels denervated by resection of both the saphenous and sciatic nerves showed significant increases in phenylephrine and potassium sensitivity. When depolarized in high-K+ solution the denervated vessels showed an increased sensitivity to extracellular Ca2+. The results show that complete short-term denervation of the rat medial plantar artery in vivo causes a pronounced supersensitivity in the vascular smooth muscle. The supersensitivity appears not to be restricted to the sympathetic alpha-receptors but also associated with changes in the cellular excitation-contraction coupling. Such altered reactivity of the vascular smooth muscle may contribute to vascular disturbances observed in vivo after nerve damage or surgical denervation.

Adrenergic alpha-Agonists↗

Vibrotactile sense and hand symptoms in blue collar workers in a manufacturing industry.

OBJECTIVES: To study whether vibrotactile sense combined with questionnaires (subjective complaints) and a clinical examination (including scoring of the Stockholm workshop scale (sensorineural staging)) could serve as a screening procedure, in the health care service, for sensorineural symptoms. A group of blue collar workers exposed to vibration in a manufacturing industry (rock crushing plants) was used as the study group. Another group of workers not exposed to vibration but subjected to heavy manual work served as the control group. METHODS: Vibrotactile sense was determined. The index and the little fingers of both hands were investigated. A clinical examination was performed. Questionnaires were used for exposure data and for assessment of symptoms. RESULTS: Important findings were that impairment in vibrotactile sense correlated with impairment in grip force, cold sensitivity, and other sensorineural symptoms--such as numbness and tendency to drop items. Clinical findings such as Phalen's test and two point discrimination were related only in those workers with the poorest vibrotactile sense. There was a relation between vibrotactile sense and the Stockholm workshop scale (sensorineural staging) for the sensorineural symptoms. Muscle and joint problems were more often seen in workers with decreased vibrotactile sense. CONCLUSIONS: Tactilometry for assessment of vibrotactile sense is a useful tool in assessing and evaluating the severity of vibration induced neuromuscular symptoms and verifying the patients' clinical complaints. Heavy manual work without exposure to vibration may contribute to impairment of vibrotactile sense. The relation between impairment in vibrotactile sense and grip strength indicates that impaired sensory feedback may contribute to muscle weakness.

Adolescent↗

Structural nerve changes at wrist level in workers exposed to vibration.

OBJECTIVES: To analyse the character of morphological changes occurring in a well defined peripheral nerve in humans exposed to vibration from hand held tools. METHODS: Biopsies of the dorsal interosseus nerve just proximal to the wrist were taken from 10 men exposed to vibration and from 12 male age matched necropsy controls. The nerve was resected for pain relief either as the sole procedure or in conjunction with carpal tunnel release. All specimens were sectioned and examined by light microscopy in standard sections, thin epon sections, and teasing preparations. RESULTS: The combined results of the analyses showed pathological changes in all 10 patients dominated by breakdown of myelin and by interstitial and perineurial fibrosis. All but one of the 12 controls were normal. CONCLUSION: These findings often show severe nerve injury previously not described at this level. They indicate that demyelination may be the primary lesion in neuropathy induced by vibration followed by fibrosis associated with incomplete regeneration or with organisation of oedema. Vibration can induce structural changes in peripheral nerves just proximal to the wrist and such changes may constitute a structural component in carpal tunnel syndrome among people exposed to vibration. This may help to explain the poor results achieved by carpal tunnel release in these patients.

Adult↗

Nerve injury induced by vibration: prevention of the effect of a conditioning lesion by D600, a Ca2+ channel blocker.

OBJECTIVES: Exposing a hind leg of a rat to vibration induces an injury to the sciatic nerve--a so called conditioning lesion. After such injury induced by vibration the regenerative capacity of the nerve is improved and can be detected as an increased axonal outgrowth from a test crush lesion to the same nerve. The purpose was to study whether the effect of a conditioning lesion induced by vibration can be prevented by local treatment with a Ca2+ channel blocker D600. METHODS: D600 (methoxyverapamil) or Ringer's solution was locally applied to the sciatic nerve on one side through a silicone tube connected to a miniosmotic pump, which was implanted subcutaneously. During the same period the hind leg was exposed to vibration (80 Hz; 32 m/s2 root mean squared) for five hours daily for five consecutive days. The other hind leg was not vibrated. After the end of exposure to vibration the sciatic nerves were crushed bilaterally (test crush lesions) and three or six days later the regeneration distances of sensory axons were measured by the pinch reflex test. RESULTS: Nerves in the control animals (without implanted miniosmotic pumps and nerves on to which Ringer's solution was locally applied) that were exposed to vibration showed a significantly increased outgrowth length of sensory axons from the test crush lesion compared with the non-vibrated side. Such an effect of a conditioning lesion from the exposure to vibration was suppressed by local application of D600. CONCLUSIONS: Local administration of a Ca2+ channel blocker D600 can prevent the effect of a conditioning lesion-that is, the nerve injury induced by vibration can be inhibited by D600. This may have implications for the treatment of patients with neuropathy of the hand induced by vibration.

Animals↗

Bioartificial nerve grafts based on absorbable guiding filament structures--early observations.

Gaps 10 mm wide in the sciatic nerves of 64 rats were bridged by bioartificial nerve grafts consisting of a silicone tube containing seven longitudinally placed filaments made of non-absorbable, (polyamide [Ethilon]) or absorbable, material (polydioxanone [PDS], polyglactin [Vicryl], and catgut). The purpose was to study the organisation of axonal growth inside the tube along such filaments. After two and four weeks histological techniques were used to study the contents of the tube and at four weeks immunohistological techniques were used to confirm the presence of axons distal to the tube. In all experimental groups axons had traversed the tube and reached the distal segment after four weeks. Inside the tube axons were organised in multiple minifascicles in all groups, but there were no axons growing in direct contact with the filaments. We conclude that resorbable filaments placed inside a silicone tube do not disturb axonal growth across the tube.

Absorption↗