Conduction in Segmentally Demyelinated Mammalian Central Axons

Abstract

The prominent symptoms associated with central demyelinating diseases such as multiple sclerosis (MS) are primarily caused by conduction deficits in affected axons. The symptoms may go into remission, but the mechanisms underlying remissions are uncertain. One factor that could be important is the restoration of conduction to affected axons, but it is not known whether demyelinated central axons resemble their peripheral counterparts in being able to conduct in the absence of repair by remyelination. In the present study we have made intraaxonal recordings from central axons affected by a demyelinating lesion, and then the axons have been labeled ionophoretically to permit their subsequent identification. Ultrastructural examination of 23 labeled preparations has established that some segmentally demyelinated central axons can conduct, and that they can do so over continuous lengths of demyelination exceeding several internodes (2500 m). Such segmentally demyelinated central axons were found to conduct with the anticipated reduction in velocity and a refractory period of transmission (RPT) as much as 34 times the value obtained from the nondemyelinated portion of the same axon; the RPT was typically prolonged to 2-5 times the normal value. We conclude that some segmentally demyelinated central axons can conduct, and we propose that the restoration of conduction to such axons is likely to contribute to the remissions commonly observed in diseases such as MS. Key words: demyelination; multiple sclerosis; axon; conduction properties; glia; ionophoresisMultiple sclerosis (MS) is a disease of the C NS in which affected central axons often lose one or more internodes of their myelin sheath; the continuity of the axon through the lesion is frequently maintained, although degeneration becomes more prominent as the disease progresses (McDonald, 1994). The disease is associated with symptoms such as paralysis, blindness, and numbness, which can be explained by conduction block in the relevant pathways. Such symptoms may spontaneously go into remission; however, the mechanisms underlying such remissions are not well understood. It is now clear that some demyelinated lesions are partially repaired by remyelination and that this phenomenon can be quite common and extensive in early lesions (Prineas et al., 1993a). Remyelination is known to restore secure conduction to central (Smith et al., 1979(Smith et al., , 1981Blight and Young, 1989;Felts and Smith, 1992;Honmou et al., 1996) and peripheral (Saida et al., 1980;Smith and Hall, 1980;Sedal et al., 1983;Shrager, 1988) demyelinated axons, and it is reasonable to believe that conduction in remyelinated central axons will contribute to remissions; however, even where remyelination occurs in MS, it may be temporary (Prineas et al., 1993b), and persistently demyelinated lesions are a common feature of the disease. It is known that some of these persistently demyelinated lesions are clinically silent, i.e., they do not produce symptoms (Ghatak et al., 1974;Phadke and Best, 1983; f...

Extensive remyelination of the CNS leads to functional recovery

“…The restoration of the myelin sheath both by endogenous oligodendrocyte precursor cells (OPCs) and from exogenous sources of OPCs or Schwann cells has been shown unequivocally to restore conduction in affected fibers (10,11). It is clear that the resulting thin myelin sheaths and shorter internodes support fast and secure saltatory conduction, even in axons with as few as 5 lamellae (12).…”

Cognitive dysfunctions associated with white matter damage due to cardiovascular burden – determinants and interpretations

“…If the neural tissue is not broken, demyelinated axon conducts potentials but in significantly changed temporal organization. Even partially demyelinated axons transmit the signals with reduced velocity, and their refractory period of transmission is about 34 times prolonged that the value obtained from normal myelinated axon (Felts et al, 1997). Those data indicate that ischemic white matted damage leads to slowdown and dysregulation in the information transmission process on the basic physiological level.…”

“…White mater is prone to ischemic damage in a form of a myelin shrinking. Felts et al (1997) and later Sinha et al (2006) stated that myelin damage does not always mean total interruption of signal transmission in axons -what is assumed a priori in disconnection models. If the neural tissue is not broken, demyelinated axon conducts potentials but in significantly changed temporal organization.…”

A PET study on the characterization of partially reversible radiogenic lower motor neurone disease

“…Conduction can be restored in some chronically demyelinated axons that acquire a higher than normal density of sodium channels. 44,45 The modi®ed molecular structure and conducting mechanism of these internodal segments give rise to an extra energy requirement, as a larger number of sodium channels allows a larger displacement of intraaxonal ion concentrations during the propagation of the action potential. The pumping-out of extra amounts of intracellular sodium against a concentration gradient will demand an increased amount of energy.…”