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M Rasminsky

Publications and source records attributed to M Rasminsky.

33 records · Page 2Linked to original sources

Physiological properties of dystrophic mouse spinal root axons.

In the spinal root axons of dystrophic mice conduction of nerve impulses is slow and either saltatory or continuous, presumably corresponding to areas of myelination and amyelination respectively. These abnormally myelinated axons contain foci of hyperexcitability manifested by spontaneous ectopic excitation, ephaptic excitation and autoexcitation. Similar phenomena in demyelinated central and peripheral nerve fibres may underly positive neurological symptomatology in human peripheral and central demyelinating diseases (Rasminsky 1981, 1982).

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Ephaptic transmission between single nerve fibres in the spinal nerve roots of dystrophic mice.

1. Ephaptic transmission was observed between spontaneously active single nerve fibres in the spinal nerve roots of dystrophic mice. 2. In the five ephaptically interacting pairs of fibres studied in detail, the conduction velocities in the exciting fibres were < 1 m/sec and the conduction velocities in the excited fibres were 2-10 m/sec in the immediate vicinity of the ephapses at 26-28 degrees C. 3. Membrane current analysis suggested that conduction was continuous in the exciting fibres. In some cases conduction away from the ephapse in the excited fibre was saltatory in at least one and possibly in both directions of transmission. 4. It is concluded that in at least some cases the direction of ephaptic transmission is from bare axon to myelinated axon. 5. Transmission time across the ephapses, measured as the interval between peaks of inward membrane current in exciting and excited fibres, was less than or equal to microseconds-240 microseconds. 6. Ephaptic transmission is not necessarily contingent upon the direction of propagation of the impulse in the exciting fibre. 7. Ephaptic transmission between two fibres can remain stable at frequencies of at least 70 Hz. 8. There may be multiple sites of spontaneous ectopic excitation in single dystrophic mouse spinal root axons. An impulse traversing a site of ectopic excitation may incite a subsequent burst of impulses to arise from that site following a delay of more than 100 msec.

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Node-like areas of intramembraneous particles in the unensheathed axons of dystrophic mice.

The unensheathed axons in the spinal roots of adult dystrophic mice were examined by freeze-fracture electron microscopy. In most areas of these abnormal fibers the distribution of intramembraneous particles was similar to that of the internodal segments of normal axons with many more particles on the PF (internal) leaflets of these axonal surface membranes than on their EF (external) leaflets. However, patches of axonal membranes were also observed in which the distribution of intramembraneous particles resembled that seen in nodes of Ranvier.

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Conduction of nervous impulses in spinal roots and peripheral nerves of dystrophic mice.

Conduction was studied in the sacral ventral roots and ventral tail nerves of dystrophic mice (dy/dy) and phenotypically normal littermates. In myelinated ventral root fibers of normal mice, conduction velocity was uniform with internodal conduction time 45 +/- 5 musec (26 degrees C). In ventral root fibers of dystrophic mice, conduction velocity was decreased and strikingly non-uniform; both saltatory and continuous conduction were observed in different portions of the same nerve fiber. Continuous conduction with velocity less than 2 m/sec (26 degrees C) was characteristically observed in mid-root where the axons are bare; conduction was saltatory close to the exit from the spinal canal and near the spinal cord where the axons are myelinated. Maximum conduction velocity in ventral tail nerves was 21 +/- 3 m/sec for dystrophic mice and 31 +/- 4 m/sec for littermate controls (37 degrees C). Internodal lengths were somewhat decreased in the dystrophic peripheral nerves but there was no significant difference in maximum fiber diameters, myelin thickness or nodal morphology between dystrophic and normal nerves.

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Ectopic generation of impulses and cross-talk in spinal nerve roots of "dystrophic" mice.

In "dystrophic" mice, many spinal root axons are bare and closely apposed to one another in midroot. The direction of nerve impulse traffic in lubosacral spinal nerve roots was determined by biphasic recording of spontaneous activity. In normal mice, impulse traffic in dorsal and ventral roots is directed toward and away from the spinal cord, respectively. However, in spinal root fibers of dystrophic mice, impulses also originate in midroot and are propagated toward both the spinal cord and the periphery. Impulses originate in midroot as single isolated events, in bursts at frequencies of up to 100 Hz, or as continuous activity persisting for several minutes in single fibers. Ectopically arising activity in some single fibers is consistently associated with transmission of an impulse in another fiber past the site of origin of the ectopically arising impulse. Thus impulses arise in the spinal root axons of dystrophic mice both spontaneously and as a result of cross-talk between single fibers.

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Complications of phenol neuroloysis.

Phenolic stellate ganglion blockade caused triparesis in one patient, and phenolic neurolysis of cervical posterior roots caused respiratory arrest in another. These complications illustrate the dangers of the spread of phenol beyond the intended site of neurolysis with resultant local anesthesia, direct neural damage, vascular damage, and infarcts.

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Internodal conduction in undissected demyelinated nerve fibres.

1. A new method is described for recording external longitudinal currents from single undissected nerve fibres in rat ventral roots. The method permits identification of the sites of fifteen or more successive nodes of Ranvier in a given single fibre and the measurement of internodal conduction times between them.2. Average internodal conduction time for normal ventral root fibres of internodal length between 0.75 and 1.45 mm is 19.7 +/- 4.6 (S.D.) musec at 37 degrees C. Internodal conduction time appeared to show a minimum for fibres of internodal length 1.0 mm.3. Ventral roots were demyelinated by focal application of diphtheria toxin. Although conduction is markedly slowed in demyelinated fibres, sites of inward membrane current remain spatially separated indicating that conduction remains saltatory to the point of conduction block rather than becoming continuous as in unmyelinated fibres.4. Slowing of conduction appears to be due to changes in the passive electrical properties of the internodal myelin. Evidence is presented suggesting that there is an increase in internodal capacitance and a decrease in internodal transverse resistance at internodes of demyelinated fibres; such changes would have the effect of delaying excitation at the nodes. The changes in passive electrical properties, which appear to be primarily in the vicinity of the nodes, would be consistent with the pathological changes observed in demyelinated fibres.5. Internodal conduction times in demyelinated fibres have ranged from normal (26 musec at 30 degrees C) to more than 600 musec. There is a great variation in internodal conduction time at successive internodes of a given single fibre; this presumably reflects the varying severity of demyelination of successive internodes.6. As in normal fibres, nodes of demyelinated fibres generate less current when excited by the second of two closely spaced impulses. This results in an increased internodal conduction time for the second impulse and, at a critically short interstimulus interval, conduction block of the second impulse.7. The increased refractory period of transmission of internodes with increased internodal conduction times is a consequence of the decreased ability of such internodes to sustain propagation in the face of small decreases in nodal current.8. During tetanic stimulation, increases in internodal conduction time are associated with corresponding decreases in nodal current generated by the node proximal to the internode in question.9. It is suggested that changes in the magnitude of the nodal current during repetitive activity are due to changes in transmembrane concentration gradients of sodium, the increased internodal conduction time and eventual conduction block during tetanic stimulation being caused by intracellular sodium accumulation.10. Intracellular sodium accumulation is also offered as the explanation for the post-tetanic depression seen in demyelinated fibres.

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A computer simulation of conduction in demyelinated nerve fibres.

1. The theoretical effects of demyelination on conduction of a propagated impulse have been examined in a computer simulated myelinated nerve fibre. Demyelination was simulated by increasing the capacitance and conductance of the myelin sheath of individual internodes or parts of internodes.2. Internodal conduction time increased as myelin thickness was decreased. The increase in internodal conduction time became more precipitous as the myelin became thinner. Propagation continued past a single demyelinated internode until myelin thickness was uniformly reduced to less than 2.7% of normal myelin thickness.3. Paranodal demyelination was more effective in slowing impulse conduction than was uniform demyelination of an entire internode with an equivalent rise in overall internodal capacitance and conductance.4. The effects on conduction of demyelination of two adjacent internodes or of two internodes separated by a normal internode were more than the sum of the effects of demyelination of each internode individually.5. Propagation across a severely demyelinated internode was blocked with an increase in internal sodium concentration which had a trivial effect on conduction in a normal fibre.6. Propagation across a severely demyelinated internode was blocked with increased temperature at a temperature at which propagation proceeds normally across normal internodes.7. The similarity between the findings of the computer simulations and the experimental findings in demyelinated fibres is discussed.

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