The pathogenesis of primary internodal demyelination produced by acetyl ethyl tetramethyl tetralin

Evidence for preserved schwann cell somal function

Arnold B. Sterman, Peter Spencer

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

The pathogenesis of primary internodal PNS demyelination produced by acetyl ethyl tetramethyl tetralin (AETT) has been studied using subchronically intoxicated rats with intact sciatic nerves (right side), and with focally traumatized nerves (left side) undergoing myelin breakdown and repair. Sixteen Sprague-Dawley rats were given approximately 50 mg/kg/d of AETT, dissolved in ethanol and placed in food. Six age-matched control animals received daily an equivalent amount of food treated with the same volume of alcohol. After six weeks and prior to the onset of demyelination, AETT treatment had increased the number of visible Schmidt-Lanterman incisures per internode of large-diameter fibers in tibial nerves. By ten weeks, the same group' of fibers had begun to develop juxtanodal and internodal myelin bubbles. Subsequently, intramyelinic phagocytes of hematogenous derivation removed entire intemodes of edematous myelin. Schwann cell response to injury was studied in control and AETT-intoxicated animals which had undergone left hindlimb surgery 1 to 2 days after beginning toxin treatment: (a) a perineurial window was placed in the peroneal nerve to induce focal demyelination and remyelination, (b) the tibial nerve was transected between ligatures to study Wallerian degeneration of the distal stump, and (c) the sural nerve was focally crushed to induce axonal regeneration and myelination. Qualitatively similar responses to nerve injury were seen 1 to 16 weeks later in AETT-treated and control animals. These results are compatible with the view that AETT damages myelin directly, that Schwann cell somal functions are not seriously affected by AETT, and that Schmidt-Lanterman incisures undergo changes prior to demyelination, which may represent a physiological response of the Schwann cell to toxic attack on its myelin sheath. Taken in concert, these observations challenge the long-held view that primary internodal demyelination is necessarily indicative of metabolic dysfunction of the Schwann cell soma.

Original languageEnglish (US)
Pages (from-to)112-122
Number of pages11
JournalJournal of Neuropathology and Experimental Neurology
Volume40
Issue number2
StatePublished - 1981
Externally publishedYes

Fingerprint

Schwann Cells
Demyelinating Diseases
Myelin Sheath
Tibial Nerve
Wallerian Degeneration
Food
Sural Nerve
Peroneal Nerve
Poisons
Wounds and Injuries
Carisoprodol
Sciatic Nerve
Hindlimb
Phagocytes
versalide
Ligation
Sprague Dawley Rats
Regeneration
Ethanol
Alcohols

ASJC Scopus subject areas

  • Clinical Neurology
  • Pathology and Forensic Medicine
  • Cellular and Molecular Neuroscience
  • Neurology
  • Neuroscience(all)

Cite this

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title = "The pathogenesis of primary internodal demyelination produced by acetyl ethyl tetramethyl tetralin: Evidence for preserved schwann cell somal function",
abstract = "The pathogenesis of primary internodal PNS demyelination produced by acetyl ethyl tetramethyl tetralin (AETT) has been studied using subchronically intoxicated rats with intact sciatic nerves (right side), and with focally traumatized nerves (left side) undergoing myelin breakdown and repair. Sixteen Sprague-Dawley rats were given approximately 50 mg/kg/d of AETT, dissolved in ethanol and placed in food. Six age-matched control animals received daily an equivalent amount of food treated with the same volume of alcohol. After six weeks and prior to the onset of demyelination, AETT treatment had increased the number of visible Schmidt-Lanterman incisures per internode of large-diameter fibers in tibial nerves. By ten weeks, the same group' of fibers had begun to develop juxtanodal and internodal myelin bubbles. Subsequently, intramyelinic phagocytes of hematogenous derivation removed entire intemodes of edematous myelin. Schwann cell response to injury was studied in control and AETT-intoxicated animals which had undergone left hindlimb surgery 1 to 2 days after beginning toxin treatment: (a) a perineurial window was placed in the peroneal nerve to induce focal demyelination and remyelination, (b) the tibial nerve was transected between ligatures to study Wallerian degeneration of the distal stump, and (c) the sural nerve was focally crushed to induce axonal regeneration and myelination. Qualitatively similar responses to nerve injury were seen 1 to 16 weeks later in AETT-treated and control animals. These results are compatible with the view that AETT damages myelin directly, that Schwann cell somal functions are not seriously affected by AETT, and that Schmidt-Lanterman incisures undergo changes prior to demyelination, which may represent a physiological response of the Schwann cell to toxic attack on its myelin sheath. Taken in concert, these observations challenge the long-held view that primary internodal demyelination is necessarily indicative of metabolic dysfunction of the Schwann cell soma.",
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