Mechanisms of differential axial blockade in epidural and subarachnoid anesthesia.

The mechanisms of persistent differential blocks that accompany subarachnoid and epidural anesthesia are clarified here with the aid of two principles derived from in vitro study of individual myelinated axons: 1) conduction can leap two consecutive blocked nodes but not three, and 2) a fiber length with more than three consecutive nodes bathed by weak anesthetic may block by decremental conduction, the requisite concentration varying inversely with the number of nodes bathed by anesthetic. Principle 1 applies in epidural blockade, where anesthetic bathes only a few millimeters of segmental nerve extradurally in the intervertebral foramen. Here, three-node block will be rare in large, long-internode fibers but likely in small, short internode fibers, thus explaining the differential retention of motor power in the presence of block of pain, which is achieved in epidural anesthesia when relatively weak solutions are used, as in obstetrics. Principle 2 may intervene in subarachnoid blockade where, cephalad to the site of puncture, increasingly concentrated anesthetic bathes increasing lengths of fibers in the craniocaudal succession of spinal nerve roots. This will produce decremental conduction block in increasingly long internode fibers in successive roots, reflected in a corresponding craniocaudal segmental sequence of blocked physiological functions: vasoconstriction, cutaneous temperature discrimination, pinprick pain sensibility, and skeletal motor activity. The segmental spatial differential sequence migrates with time but resembles the temporal differential sequence of loss seen at the onset of peripheral nerve blocks. Several other previously disparate clinical observations follow logically from the new interpretation.

Junction between parent and daughter axons in regenerating myelinated nerve: properties of structure and rapid axonal transport.

The primary aim of this work was to investigate the properties of rapid axonal transport in regenerating myelinated axons in the sciatic nerve of Xenopus laevis, with particular attention to events at the junction between the proximal, intact axon (the "parent") and the distal, newly formed axon (the "daughter"). Morphological studies indicated that all myelinated axons initiated regeneration and that at least 80% of these axons regenerated at a rate of 1 mm/day or greater (20 degrees C). The ultrastructure of the junctional region was examined at regeneration times between 3 days and 20 weeks. The main qualitative change in the junctional axoplasm over this period was in its content of particulate organelles. At times up to 2 weeks regeneration, the junction contained abnormal numbers of 50 nm diameter vesicles and 10 nm granules. Between 2 and 5 weeks the junction showed in addition a peripheral rim of large membrane-bounded organelles around a central core of microtubules and neurofilaments. At longer times the numbers of large membrane-bounded organelles diminished and all junctions contained prominent accumulations of 10 nm granules. The rate of rapid axonal transport of protein was similar in parent and daughter axons. Compared to the parent axons, a 2-5 times greater amount of protein was deposited to a stationary phase in daughter axons. Specimens of nerve that were subjected to mechanical stress during the removal of the perineurium showed a large accumulation of rapidly transported protein in the region of the crush at regeneration times up to 40 days; some of the accumulated protein was subsequently transported retrogradely. Video microscopy of isolated axons supplied evidence that the transport deficit in mechanically stressed nerve was a partial block of anterograde vesicle transport, plus a reversal of anterograde transport, at the junction of parent with daughter axons. No structural changes were detected in mechanically stressed nerve. The results show that the junction between parent and daughter myelinated axons is a region with distinct morphology at which the dynamics of anterograde axonal transport may change dramatically.

The interstitial system of the spinal trigeminal tract in the rat: anatomical evidence for morphological and functional heterogeneity.

Utilizing cyto-, myelo-, and chemoarchitecture as well as connectional criteria, the present study reveals the interstitial system of the spinal trigeminal tract (InSy-SVT) in the rat to be composed of five morphologically and functionally distinct components that are distributed within spatially restricted regions of the lateral medulla. The first component is represented by scattered interstitial cells and neuropil, which extend laterally into SVT from the superficial laminae of the medullary dorsal horn (MDH). The second component, the dorsal paramarginal nucleus (PaMd), consists of a small group of marginal (lamina I)-like neurons and neuropil situated within the dorsolateral part of SVT at the rostral pole of MDH. The third component represents a trigeminal extension of the parvocellular reticular formation (V-Rpc) into the ventromedial aspect of SVT at levels extending from rostral MDH to the caudal part of trigeminal nucleus interpolaris (Vi). The fourth component, the paratrigeminal nucleus (PaV), consists of a large accumulation of neurons and neuropil situated within the dorsal part of SVT throughout the caudal half of Vi. The fifth component is the insular trigeminal-cuneatus lateralis nucleus (iV-Cul), which is a discontinuous collection of neurons and neuropil interspersed among fibers of SVT as well as wedged between it and the spinocerebellar tract. Thalamic projection neurons are located in PaMd and V-Rpc, whereas cerebellar projecting neurons are confined to iV-Cul.

Effects of limited postnatal ethanol exposure on the development of myelin and nerve fibers in rat optic nerve.

This study was designed to morphologically evaluate the effects of limited postnatal alcohol exposure on the development of myelin and axons in the rat optic nerve. Rat pups were artificially reared on Days 5-18 with a supplemented milk diet fed via a chronic gastrostomy tube. Experimental animals received 4% ethanol in their diet on Days 5-9, otherwise the experimental and control animals received identical diets in identical volumes. Optic nerve tissues were prepared for electron microscopy on Days 10, 16, 22, 29, and 90. The cross-sectional areas of optic nerves were smaller, there were fewer myelinated nerve fibers per unit area, and the progress of myelination was slowed on Day 10 in the ethanol-exposed animals. All of these effects were compensated for at later times. The ratio of myelin thickness to axon diameter was similar in experimental and control animals, indicating that the interaction between axon size and myelin formation was not affected by alcohol. The general distribution of axon sizes was unaffected by ethanol except at 10 days when the largest fibers were smaller. There was no evidence of alcohol-induced degeneration of axons, myelin, or glial structures. Thus, alcohol exposure during myelin development causes a delay in myelin acquisition that is later compensated for.

New technique for differential staining of myelinated fibers and nerve cells on paraffin sections.

A simple, rapid method for the differential staining of myelinated nerve fibers and nerve cell bodies, applicable to sections of central nervous system pieces embedded in paraffin, is described. Experimental material fixed by perfusion with mixed aldehydes or necropsy material fixed in formaldehyde can be used. Constant and homogeneous results are obtained with this technique, and the most important characteristic is the absence of differentiation in either of the steps: staining of myelinated fibers and staining of nerve cell bodies. Sections 15 microns thick were attached to slides, dewaxed, and hydrated. After hydration, sections are mordanted (30 min) in 2.5% iron alum (SO4)2FeNH4, and rinsed (1 min) in distilled water. Staining is for 180 min in the following solution: 5 ml freshly made 20% alcoholic hematoxylin diluted with 25 ml of distilled water and 25 ml of absolute ethanol to which 10 ml of 1% Li2CO3 is added. The sections are washed in distilled water (5 min) and stained during 5 min in the following solution: 0.2% pyronine, 20% formaldehyde in distilled water. The sections are dehydrated through 96% and absolute ethanol, cleared in eucalyptol, and mounted in Eukitt. Myelinated fibers appear dark blue, whereas nerve cell bodies are stained red and the cell nucleoli dark blue. This procedure provides an adequate contrast for observation and photography.

Morphology of the cochlear nerve in Sprague-Dawley and brown Norway rats.

Cochlear nerve morphology was studied in young adult albino (Sprague-Dawley) and pigmented (Brown Norway) rats. Analysis of the material included counts of normal and degenerating fibers and of glial cell nuclei, and measurements of vascularity and of the nerves' cross-sectional areas. The median number of normal fibers in the Sprague-Dawley rats was 21,216, and, in the Brown Norway rats, it was 20,186. There were no statistically significant differences between the two strains in numbers of normal fibers, degenerating myelin sheaths, or glial cell nuclei, or in the cross-sectional areas of the nerves. The area density of blood vessels was significantly higher in nerves from the Sprague-Dawley rats. The median area density in that strain was 0.0149, while in the Brown Norway rats the median area density was 0.0105.

Effect of acclimation temperature on the axon and fiber diameter spectra and thickness of myelin of fibers of the optic nerve of goldfish.

The optic nerves of common goldfish acclimated to 5 and 25 degrees C were fixed with glutaraldehyde in either phosphate buffer or PIPES with EGTA, post-fixed with osmium tetroxide, and examined by electron microscopy. The axon diameter spectra, from axons measured in electron micrographs and those measured on the electron microscope screen, differ noticeably with acclimation temperature. At the lower temperature, there is a definite shift toward the occurrence of larger fibers compared with the spectrum of the 25 degrees C fish. Although the number of fibers assessed is small compared with the total number in the goldfish nerve, these results confirm our previous study. These findings could be attributed to an increase in the number of new fibers during the acclimation to the higher temperature. We discuss this possibility and on the available evidence find it unlikely. Other changes in the axon and fiber are also seen with acclimation temperature. The axon to fiber diameter ratio, made directly from the electron micrographs, shows that axons from the nerves of the higher acclimation temperature fish possess consistently thicker myelin sheaths than are found for axons in nerves of the lower temperature fish. This finding is also in agreement with results obtained by us from measurements independent of each other.

An efficient sampling scheme for estimating fibre number from nerve cross sections: the fractionator.

Biopsies were made on six rat tibial nerves and 'absolute' numbers of myelinated fibres determined by counting all fibres in all nerve trunks. Subsequently, two unbiased sampling schemes-systematic random quadrat (SRQ) and 'fractionator' sampling-were used to select fibres from the same nerves and to obtain estimates of their numbers. Both schemes captured roughly 200 out of the total of 3000 myelinated fibres found in these nerve trunks, all of which were sampled exhaustively, without replacement. Estimates of fibre number were derived by an established approach, the 'ratio technique' (using SRQ samples), and by a new principle, the fractionator (using fractionator samples). Counting all fibres in every nerve trunk took almost 6 hours. Both the ratio technique and the fractionator approaches provided efficient and unbiased estimates of fibre numbers. Six nerve trunks were analysed by SRQ sampling in 77 minutes, compared with 65 minutes by the fractionator. Apparent differences between the two approaches were of minor interest when set against the benefits of sampling per se. These findings are likely to be of practical concern to those wishing to examine nerves with great numbers of fibres and/or to examine large numbers of nerves.

On internodal length.

A study has been made of changes in internodal lengths in rat tibial nerves and human sural nerves with age. Myelinated fibre counts on these nerves showed that maximum numbers were reached at an early stage of development. The slope of regression lines relating internodal length to fibre diameter was relatively flat at this stage, but became steeper with increasing age. Maximum internodal length in rat tibial nerve was closely related to growth of the limb bones. Whilst this study confirms that the largest fibres are subjected to hind limb growth for the greatest period, and therefore have the longest internodes, it does not support the generally accepted view that short internodes are the consequence of the later myelination of small fibres, and hence shorter period of extension due to growth.

Adjustment of the myelin sheath to axonal atrophy in the rat spinal root by the formation of infolded myelin loops.

Atrophy of the L4 dorsal and ventral spinal roots was experimentally induced by unilateral sciatic neurectomy in groups of young (2 and 4 months) and older (12 months) albino rats. During the 4 months following neurectomy, the occurrence of infolded myelin loops (IMLs) was quantitatively examined in transverse sections prepared using perfusion fixation with glutaraldehyde and embedding in epoxy resin. The number of IMLs was higher on the operated side and increased with the time of survival and the age of the animals. The formation of IMLs is a characteristic early response of a large-caliber myelin sheath to axonal atrophy, probably reflecting the presence of redundant myelin.

The relationship between structural features of peripheral nerves and suture methods for nerve repair.

Based on techniques for identifying and distinguishing motor, sensory, and mixed fasciculi in peripheral nerves, the authors propose guidelines for selecting suture methods for nerve repair. When many mixed fasciculi are known to exist at the nerve lesion, epineurial repair is preferable; fascicular (perineurial) repair is more suitable when pure motor and sensory fasciculi are clearly recognized. Generally, epineurial repair is indicated for more proximal injuries, with fascicular repair most appropriate for more distal sites. A greater ratio of epineurial connective tissue to intrafascicular nervous tissue implies an inclination toward fascicular repair.

The intraneural distribution of myelinated fibres in the equine recurrent laryngeal nerve.

The intraneural course of nerve fibres in the equine recurrent laryngeal nerve was investigated by partially ligating the nerve at a proximal site, and 3-8 weeks later, tracing the course and spatial relationships of intact and degenerating fibres along the distal stump. This nerve was chosen because of its great length, the fact that it is a nonbranching motor nerve and because of debate about the course of abductor and adductor nerve fibres in the recurrent laryngeal nerve. Six ponies were used and in each the recurrent nerve was partially ligatured about 20 cm from the larynx, using a fine silk suture. In all there was a clear separation of intact and degenerating fibres just distal to the suture, but they became mixed close to the point of innervation of the laryngeal muscles. The numbers of intact myelinated fibres remained similar along the partially denervated nerve segment. These results suggest that myelinated fibres mix within the recurrent laryngeal nerve and that focal lesions of this nerve should not result in denervation of individual laryngeal muscles.

[Morphological changes in the electrically inactive afferent myelinated nerve fibers of the live clustered neuroreceptor]. / Morfologicheskie izmeneniia élektricheski neaktivnykh afferentnykh mielinovykh nervnykh volokon zhivogo kustikovidnogo interotseptora.

At attempt has been made to determine morphological criterium of active and inactive alive afferent myelin fibers. Applying electrophysiological control, external diameters in the area of maximal dilatation of the myelin fiber are compared with the neighbouring maximal narrowing of the unmyelinated preterminal. The dilatation coefficient, suggested by the authors of mathematical models of the nervous fiber is taken as the base of estimation. When the dilatation coefficient is more than five, the fiber is considered to be inactive. The active and inactive nervous fibers are stated to possess certain morphological differences. They are observed not only in the first myelin segment area, but in the second one, and sometimes--in the third and fourth segments. Morphological characteristics of these segments make it possible to suggest that electrical impulse can be blocked. From our data it is possible to think that not only the first myelin segment and the first node of Ranvier, but also the successive segment and nodes of Ranvier influence the impulse passing.

Immunohistochemical demonstration of nociceptors in the capsule and synovial folds of human zygapophyseal joints.

Substance P, a physiologically potent neuropeptide, is considered to participate in nociceptive transmission of nerve impulses. Substance P immunofluorescent nerves are demonstrated in the inferior joint recess capsule and its synovial folds in human lumbosacral zygapophyseal joints. This may have clinical significance in spinal pain.

Myelinated and nonmyelinated nerves: comparison of proton MR properties.

The magnetic resonance (MR) relaxation rates of protons were compared in the myelinated and nonmyelinated nerves of the garfish. The long, large olfactory nerve of the garfish, as an easily accessible source of nonmyelinated axons, is uniquely suited for such a comparison. The T1 and T2 measurements revealed distinct and consistent differences between nonmyelinated olfactory nerves and myelinated optic and oculomotor nerves. Comparisons between water content, lipid content, and relaxation rates indicated that the differences in MR properties represent complex differences in the distribution and physical environment of the constituent lipid and water protons.

Human zygapophyseal joint capsule and synovial fold innervation.

The anatomy of human lower lumbar zygapophyseal joint postero-medial fibrous capsules, and their synovial folds, was investigated by high-power light microscopy and transmission electron microscopy. A description of nerves in the postero-medial joint capsule and the synovial folds is presented. The diameter of paravascular myelinated nerve fibres in the synovial folds was 0.2 micron (micron). Small myelinated nerves (0.6 to 12 microns) course through the synovial folds, not in association with blood-vessels, suggesting that these nerves are nociceptive and, therefore, may have clinical significance in spinal pain.

Distribution of myelinated nerves in ascending nerves and myenteric plexus of cat colon.

The parts of the colon differ in motor function and in responses to extrinsic and intrinsic nerve stimulation. The distribution of myelinated nerve fibers in the colonic myenteric plexus is not known. Because these fibers might be largely extrinsic in origin, their distribution might indicate the domain of influence of extrinsic nerves and help to explain the different behaviors of the different parts of the colon. Myelinated fibers were examined by electron microscopy in cross sections of the ascending nerves and in myelin-stained whole-mount preparations in the colon. The ascending nerves are much like one another. They have the structure of peripheral nerves, not that of myenteric plexus. The proportion of myelinated fibers in the ascending nerves declines rostrad with no uniform change in total nerve fiber number. Cross-sectional areas of ascending nerves, 3,304 to 7,448 microns 2; total number of nerve fibers per profile, 703-2,651; and mean myelin coat thickness, 0.45 +/- 0.01 micron, do not change uniformly along the ascending nerves. Myelinated fibers are about 2% of total fibers in the extramural colonic nerves, 7-9% in the ascending nerves in the sigmoid colon, and 2-3% at the rostrad ends of the ascending nerves in the transverse colon. Blood vessels lie at the core of each ascending nerve and on the nerve sheath. Myelinated fibers in the ascending nerves degenerate after section of colonic branches of the pelvic plexus and after section of the pudendal nerves, indicating that myelinated nerves reach the colon through both pathways.(ABSTRACT TRUNCATED AT 250 WORDS)