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Competence of nerve tissue as distal insert promoting nerve regeneration in a silicone chamber.

A new peripheral nerve forms across a 10 mm gap within a silicone chamber regeneration model when the distal segment of a transected sciatic nerve, connected to its end organs, is sutured into the distal end of the chamber. We have tested the ability of other tissue inserts to support axonal regeneration in the chamber. When an isolated 2 mm piece of sciatic nerve was sutured into the distal end, fibrin matrix formation, cell immigration and axonal regeneration were identical to those occurring in the control. When the distal nerve insert was replaced with a 2 mm piece of skin or a ligation, a matrix did not form and subsequent cell immigration and axonal regeneration did not occur. When a 2 mm piece of tendon was inserted, a matrix did form at 1 week, but a structure across the gap was observed at later time periods in only 2 out of 7 chambers. The matrix either dissolved before cells could enter the chamber or did not promote cellular immigration and subsequent axonal regeneration. When the distal end was left open, a matrix formed and cells from the reactive tissue outside the chamber entered the matrix and formed a granulation tissue bridge across the gap. This tissue failed to support axonal regeneration; at 3 weeks, axons stopped 1 mm beyond the proximal stump at the interface with the granulation tissue. Thus, matrix formation and a cellular bridge are necessary but not sufficient to ensure regeneration. Successful regeneration across the silicone chamber gap requires humoral and/or cellular contributions available from peripheral nervous tissue and not from the other tested tissues.

Animals↗

Effect of dental amalgam restorations on the mercury content of nerve tissues.

In an autopsy study in two men and an experimental study performed on three female beagles the mercury burden of nerve tissues was determined. Nerve tissues from the head and face region and from three peripheral nerves were analyzed for mercury content with the aid of atomic absorption spectroscopy. In the dogs dental amalgam restorations were placed so as to investigate the possible influence from the amalgam on the mercury content of the tissues under study. The mercury content in man and dogs differed widely from one nerve to another, with no apparent relation to the number, type, or location of tooth restorations.

Aged↗

Response of amputated rat limbs to fetal nerve tissue implants and direct current.

We have previously shown that implanted fetal nerve tissue stimulates the regeneration of amputated chick limbs. The purpose of this study was to determine whether a similar phenomenon would occur in amputated rat limbs and if addition of applied direct current (DC) would affect this process. Thus, fetal nerve tissue was implanted into amputated stumps of 3-week-old rats; variable tissue regeneration was induced that was dependent on the age of the donor implant and the presence of applied DC. Twelve or 14 day fetal neural implants induced new accessory bones containing epiphyseal plates and marrow cavities and occasionally formed joint-like structures with the host humerus. Addition of DC to 12 day neural implants increased the number of new bones formed. Eighteen day neural tissue with applied DC did not induce new bone formation but stimulated the maximal elongation of the host humerus and outgrowth of nerve fibers to the cut surface. Implantation of fetal heart tissue or implantation of fetal neural tissue into unamputated limbs failed to induce new bone formation. Although true limb regeneration was not achieved, formation of new skeletal elements did occur and this effect was enhanced by applied DC.

Amputation Stumps↗

Alanine formation and alanine aminotransferase activity in the nerve tissue with proliferating macroglia.

In the nerve tissue with proliferating macroglia cells were observed a lowered oxygen consumption, an increased aerobic glycolysis and alanine formation and a higher alanine aminotransferase and glutamate dehydrogenase activity than in the control tissue in the homogenates and in the cell sap fraction. The substrate saturation curves, apparent Km and pH optimum values in the tissue with proliferating macroglia and in the control did not differ from one another. The authors assume that a higher alanine aminotransferase activity in the tissue with macroglia proliferation can reflect either a higher synthesis of the enzyme in the altered tissue, or a predominance of glial elements in the altered tissue possessing a higher alanine aminotransferase activity than the nerve cells.

Alanine↗

Guillain-Barré syndrome: demonstration of antibodies to peripheral nerve tissue.

Sera from 30 patients with acute Guillain-Barré syndrome were tested for the presence of antibodies to peripheral nerve tissue using the antiglobulin consumption test. An increased binding of IgG was observed in 15 out of 30 sera and in these sera F(ab')2 fragments prepared from IgG retained the capacity to combine with peripheral nerve tissue, suggesting an antigen-antibody interaction. The specificity for peripheral nerve tissue was demonstrated by absorption experiments. F(ab')2 fragments prepared from IgG of normal sera, however, failed to react with the tissue, suggesting a non-specific binding through the Fc part of the molecule. In sera from patients fully recovered from the Guillain-Barré syndrome and from patients with other neuropathies, no increased binding of IgG was observed.

Acute Disease↗

Porous chitosan tubular scaffolds with knitted outer wall and controllable inner structure for nerve tissue engineering.

In this study, a novel method was developed to create porous tubular scaffolds with desirable mechanical properties and controllable inner structure from chitosan, for nerve tissue engineering. Chitosan fiber-based yarns were first used to create porous hollow tubes, which served as the outer wall of the scaffolds, through an industrial knitting process. Then, an innovative molding technique was developed and used to produce inner matrices with multiple axially oriented macrochannels and radially interconnected micropores. Acupuncture needles were used as mandrels during molding to improve the safety and controllability of the process. In vitro characterization demonstrated that the scaffolds possessed suitable mechanical strength, porosity, swelling, and biodegradability for applications in nerve tissue engineering. In vitro cell culture experiments showed that differentiated Neuro-2a cells grew along the oriented macrochannels and the interconnected micropores were beneficial for nutrient diffusion and cell ingrowth to the scaffold's interior. Collectively, the well-defined architectural features in addition to the desirable mechanical and biological properties of the scaffolds make them promising for nerve tissue engineering.

Animals↗

Phospholipid analysis of mammalian optic nerve tissue: a 31P nuclear magnetic resonance spectroscopic study.

Phospholipids of optic nerve (n = 30) from 5.6-kg rabbits were analyzed by 31P nuclear magnetic resonance (NMR) spectroscopy. Phospholipid metabolites detected were as follows (mol %): phosphatidylcholine (PC; 25.82 +/- 0.12), PC plasmalogen/alkylacyl PC (2.07 +/- 0.13), sphingosylphosphorycholine (1.12 +/- 0.20), phosphatidylinositol (PI; 2.17 +/- 0.21), lyso PC (0.85 +/- 0.06), sphingomyelin (12.52 +/- 0.10); phosphatidylserine (PS; 14.38 +/- 0.11), phosphatidylethanolamine (8.98 +/- 0.11), ethanolamine plasmalogen (28.99 +/- 0.30), unidentified phospholipid (1.10 +/- 0.01), phosphatidic acid (PA; 1.72 +/- 0.06), and lyso PS (0.28 +/- 0.10). The bulk of the ethanolamine phosphatide is in the form of its plasmalogen, which is the major phospholipid detected. The choline plasmalogen, or a reduced derivative thereof, also is present; thus, a significant phospholipid biosynthetic pathway for optic nerve tissue involves the plasmalogen route, which is a pathway distinct from the PA route responsible for the synthesis of PS, PI, and PC. This new 31P NMR lipid analytical technique offers potential for studying optic nerve phospholipid metabolism and degenerating optic nerve tissue, since the technique can accurately quantitate (1) both plasmalogen and nonplasmalogen phospholipids, (2) minor phospholipid components, and (3) previously undetected phospholipids.

Animals↗

Lipids from nerve tissues of the horseshoe crab, Limulus polyphemus.

1. The predominant lipids of nerve cords, ganglion and brain from horseshoe crabs were cholesterol (11% of lipid) and phospholipid (81% of lipid). 2. Major phospholipids were phosphatidyl ethanolamine and phosphatidyl choline with lesser amounts of phosphatidyl serine and phosphatidyl inositol and sphingomyelin. 3. The phospholipid fraction was characterized by a high content of plasmalogen, i.e. alk-1-enyl acyl phosphatides, so that 42% of the ethanolamine phosphatides were the plasmalogen, phosphatidal ethanolamine. 4. Phosphatidyl choline and phosphatidyl ethanolamine were high in polyunsaturation with 20:4 and 20:5 major fatty acids. Sphingomyelin had predominantly long chain saturated fatty acids. 5. Cerebrosides and gangliosides, which are associated with vertebrate nerve tissues, were absent from nerves of horseshoe crabs.

Animals↗

An ultrastructural study of methyl ethyl ketone's effect on cultured nerve tissues.

Clinical and experimental animal studies have firmly established that concomitant exposure to methyl ethyl ketone (MEK) and n-hexane accelerates the onset and severity of hexacarbon neuropathy. This phenomenon was demonstrated recently in an organotypic tissue culture system, consisting of mouse nerve and muscle co-cultures (Veronesi et al., 1984). This study also reported that cultures exposed to noncytotoxic doses of MEK alone and in combination with n-hexane developed intra-axonal inclusions containing axoplasmic debris. The present study was undertaken to detail further the morphological effects of MEK on cultured nerve tissue. Explants of mouse spinal cord with attached dorsal root ganglia were treated with MEK (300 micrograms/ml) for periods of 7 weeks and sampled intermittently for electron microscopy. Early and persistent morphological changes seen in the cytoplasm of both motor and sensory neurons included dispersed Nissl bodies and swollen granular endoplasmic reticulum. Both central and peripheral axons contained excessive agranular reticulum, swollen with a translucent material. In later stages, foci of axoplasmic debris developed, encircled by membranous profiles. These changes suggest that in culture, MEK affects neuronal metabolism and displays neurotoxic properties after prolonged exposure.

Animals↗

Autoantibody to nerve tissue in a patient with a peripheral neuropathy and an IgG paraprotein.

The antibody activity of a benign IgG lambda paraprotein to nerve tissue in a case of peripheral neuropathy has been investigated using immunohistochemical methods on tyrpsin-treated, formalin-fixed, paraffin-embedded tissue. IgG lambda was found in th sural nerve biopsy of the patient. Specific binding of the purified IgG lambda paraprotein and its isolated F(ab')2 fragment to homologous nerve and brain tissue was demonstrated. Similar activity was not demonstrable on fresh frozen cryostat sections. The results suggest that tests for autoantibodies to nerve tissue in neuropathological disorders should not be confined to fresh frozen tissue substrates.

Autoantibodies↗

Three-dimensional imaging of nerve tissue by x-ray phase-contrast microtomography.

We show that promising information about the three-dimensional (3D) structure of a peripheral nerve can be obtained by x-ray phase-contrast microtomography (p-microCT; Beckmann, F., U. Bonse, F. Busch, and O. Günnewig, 1997. J. Comp. Assist. Tomogr. 21:539-553). P-microCT measures electronic charge density, which for most substances is proportional to mass density in fairly good approximation. The true point-by-point variation of density is thus determined in 3D at presently 1 mg/cm3 standard error (SE). The intracranial part of the rat trigeminal nerve analyzed for the presence of early schwannoma "microtumors" displayed a detailed density structure on p-microCT density maps. The average density of brain and nerve tissue was measured to range from 0.990 to 0.994 g/cm3 and from 1.020 to 1.035 g/cm3, respectively. The brain-nerve interface was well delineated. Within the nerve tissue, a pattern of nerve fibers could be seen that followed the nerve axis and contrasted against the bulk by 7 to 10 mg/cm3 density modulation. Based on the fact that regions of tumor growth have an increased number density of cell nuclei, and hence of the higher z element phosphorus, it may become possible to detect very early neural "microtumors" through increases of average density on the order of 10 to 15 mg/cm3 by using this method.

Animals↗

Responses to a clinical test of mechanical provocation of nerve tissue in whiplash associated disorder.

Involvement of nerve tissue may contribute to the persistence of pain following a whiplash injury. This study aimed to investigate responses to the brachial plexus provocation test (BPPT) in 156 subjects with chronic whiplash associated disorder (WAD) with and without associated arm pain and 95 asymptomatic control subjects. The range of elbow extension (ROM) and visual analogue scale (VAS) pain scores were measured. Subjects with chronic WAD demonstrated significantly less ROM and higher VAS scores with the BPPT than the asymptomatic subjects (P<0.001). These effects occurred bilaterally. Within the whiplash population, subjects whose arm pain was reproduced by the BPPT demonstrated significantly less ROM on both the symptomatic and asymptomatic sides when compared to the whiplash subjects whose arm pain was not reproduced by the BPPT (P=0.003) and significantly less ROM and higher VAS scores than those whiplash subjects with no arm pain (P=0.003, 0.01). Only the whiplash subjects whose arm pain was reproduced by the BPPT demonstrated differences between the symptomatic and asymptomatic sides. These generalized hyperalgesic responses to the BPPT support the hypothesis of central nervous system hypersensitivity as contributing to persistent pain experienced by WAD patients.

Adult↗

Hydro-jet cutting: a method for selective surgical dissection of nerve tissue. An experimental study on the sciatic nerve of rats.

The aim of this study was to answer the question: is it possible to save motor nerves when dissecting tissue with the hydro-jet dissector? In order to study the influence of the hydro-jet on motor nerves the function of the sciatic nerves of 10 Wistar rats was evaluated. The sciatic nerves were dissected bilaterally and only the left one was exposed to the hydro-jet. The water-jet emerged from a nozzle with a diameter of 0.1 mm and was applied to the nerve for 2, 5 or 10 s and with jet pressures of 80, 85 and 90 bar, respectively. After the operation the animals were observed for 5 months in order to monitor the degree of limping using a scale with 10 clinical grades of function. Five months postoperatively the animals were sacrificed and the sciatic nerves were studied by light and electron microscopy. It was found that hydro-jet pressures of 80 bar and exposure times of 2 s had already lead to irreversible damage to the sciatic nerve. Therefore further studies with lower pressures or shorter exposure times are required before considering hydro-jet cutting for parotid gland surgery. It must be confirmed as harmless to motor nerves before applying this method in humans.

Animals↗

Allyl chloride-induced time dependent changes of lipid peroxidation in rat nerve tissue.

To accurately know the time-dependent changes of the lipid peroxidation and antioxidative status for elucidating the mechanism of neuropathy induced by allyl chloride (AC), the malondialdehyde (MDA), anti-reactive oxygen species (anti-ROS), glutathione (GSH), catalase (CAT), glutathione peroxidase (GPx) and superoxide dismutase (SOD) were investigated in cerebrum, spinal cord and sciatic nerve of rats after 0, 3, 6, 9, 12 weeks of AC administration. AC was administrated to Wistar rats by gavage at a single dosage of 200 mg/kg/per dose (three times per week). Rats were sacrificed after 0, 3, 6, 9, 12 weeks of treatment, and cerebrum, spinal cord, sciatic nerves were dissected, homogenized and used for the determination of lipid peroxidation and antioxidative status. The results showed that MDA in cerebrum (112.4%) and sciatic nerve (113.1%) significantly increased (P<0.05) on third week of AC treatment and at gait score of 2, and further changes of MDA were observed after 6, 9, 12 weeks and at gait score of 3, 4. While a decrease (P<0.05) in the activities of GSH, CAT, GPx and SOD after 6, 9, 12 weeks intoxication and at gait score of 2, 3, 4 were observed in cerebrum, spinal cord and sciatic nerve. Anti-ROS activities also decreased in all three nerve tissues after 3, 6, 9, 12 weeks intoxication and at gait score of 2, 3, 4. Thus, AC intoxication was associated with elevation of lipid peroxidation and reduction of antioxidative status, and the time-dependent changes of these indexes in Wistar rats nerve tissues occurred. Sciatic nerve was the main target tissue and MDA was most sensitive among all indexes. The changes of lipid peroxidation and antioxidative status might be related to the degradation of nerve fiber and served as one of mechanisms of toxic neuropathy induced by AC.

Allyl Compounds↗