Bunge Mary B, Bunge RP and Ris H : Ultrastructural Study of Remyelination in Experimental Lesion in Adult Cat Spinal Cord. J Biophys Biochem Cyto 10:67-94, 1961.
After diagnosis in 1967 I was told I would never recover and I didn’t have long … then I found this journal article. Doctors assured me there is no repair of damage in the central nervous system so the word remyelination jumped off the page and Mary Bunge’s work has been the foundation of all my recovery strategies. In this study with adult cats lesions were induced by cerebrospinal fluid exchange, a system still used for spinal cord research. Inspection of electron microscope slides of spinal tissue revealed … an occasional myelin sheath is first seen at 19 days; by 64 days, all axons are at least thinly myelinated. These observations suggest that myelin is reformed in the lesion in the same way it is first formed during normal development.
Bunge observed the condition of the experimental animals that survived …
The neurological condition of the experimental animal begins to improve at a time when remyelination begins and has returned to normal by the time most axons are at least thinly remyelinated. p81 As a farm kid I had seen injured animals recover and knew I had done it the same way! I expected to recover, I kept trying to move, and I had lots of naps. Veterinary researchers assured me that adult cats and humans are in the same biological class – “large mammals,” and that what had happened to the cats could happen to humans. Sadly, it seems no human researchers were raised on farms, or ever spoke with veterinarians.
Feigin I and Popoff N: Regeneration of Myelin in Multiple Sclerosis. Neurol 16: 364-372, 1966.
Nerve fibers myelinated by peripheral myelin were found within plaques in five cases of multiple sclerosis. These fibers were present singly, in small clusters, and, occasionally, in large groups. p364.
… did not exceed 10 % of the number thought to be demyelinated … found only within plaques, not in normal tissues … … remissions observed in many cases in which no remyelination observed
[curious – 4 of 5 cases of remyelination were women, while mostly men with little or no regeneration of myelin, in other 18 cases …. em]
The regeneration of myelin may play a role in the clinical remissions of multiple sclerosis … if ways were found to enhance the regeneration observed in this study, a clinically useful purpose might be served.
Patten Bradley M (1958) Foundations of Embryology. McGraw-Hill Book Company, Inc. New York London Toronto. [Text for embryology course I took when expecting JoAnn.]
Cerebrospinal Conduction Paths. p351
Phylogenetically these [cerebrospinal] conduction paths in the peripheral part of the cord increase in conspicuousness concomitantly with the increasing extent to ‘which the brain assumes a co-ordinating control over the basic reflexes which constitute the primary function of the cord.
MY TRANSLATION
During development, the “white matter” or myelin, in the motor part of the cord, develops as the brain assumes control over basic reflexes.
In other words, attention to movement promotes myelination.
Therefore it seemed reasonable to me, that attention to movement must also promote re – myelination. em
Bunge RP (1968) Glial Cells and CNS Myelin. Physiol Rev 48:197-251.
Myelin forms during fetal development, and, in the adult.
Hirano A, Levine S and Zimmerman HM (1968) Remyelination in the Central Nervous System after Cyanide Intoxication. J Neuropath Exp Neurol 27:234-245.
By one week after demyelination [in adult rats] we observed evidence of remyelination … until recent years, the possibility of remyelination in the central nervous system was questionable. Recently however, several fine structural studies have established this phenomenon beyond reasonable doubt. p235
Raine CS and Bornstein MB (1970) EAE: A Light and Electron Microscopy Study of Remyelination and Sclerosis in Vitro. J Neuropath Exp Neurol 29:552.
(Authors begin with credit to Bunge et al (1961) for first description of remyelination in adult cats. Tissue fragments in living mice embryo tissue cultures began to remyelinate after 8-10 days and process was well advanced by 18 days. By three weeks, almost total remyelination.
Millar J HD (1971) Multiple Sclerosis: A Disease Acquired in Childhood.
Charles C. Thomas. Springfield, Illinois, U.S.A.
If there is a normal turnover of myelin during development, then mechanisms must exist both to demyelinate and remyelinate axons. p45.
Harrison BM, McDonald WI and Ochoa J (1972) Remyelination in Central Diphtheria Toxin Lesion. J Neurol Sci 17:293-302.
… even the limited amount of remyelination observed may be sufficient to restore transmission … although conduction would still be slow in the thinly myelinated fibres, the return of the ability to conduct at all is clearly a necessary first step in the recovery of function in damaged pathways. p301.
Gledhill R, Harrison BM, MacDonald WI (1973) Demyelination and Remyelination After Acute Spinal Cord Compression. Exp Neurol 38:472-487.
Remyelination in cats commenced 7-21 days after demyelination and majority of demyelinated fibres showed evidence of remyelination by 1 month.
Ghatak NR, A Hirano, H Lijtmaer and HA Zimmerman (1974) Asymptomatic Demyelinated Plaques in the Spinal Cord. Arch Neurol 30:484-486.
Poor correlation between lesions and clinical symptoms in MS … extent of lesions in MS frequently far greater than would be anticipated from the clinical assessment.
Ghatak NR, Leshner RT, Price AC and Felton WL (1989) Remyelination in the human nervous system. J Neuropath Exp Neurol 48(5):507-518.
Thinly myelinated axons play role in continuous conduction … flu like … substantial remyelination possible in MS. Remyelination is often considered as a possible explanation for remission in MS. To our knowledge, clinically significant functional recovery as a result of remyelination has not been documented in humans.
BDJ Miller, K Asakura and M Rodriguez (1995) Experimental Strategies to Promote Central Nervous System Remyelination in Multiple Sclerosis: Insights Gained From the Theiler’s Virus Model System. Mini-Review. J Neurosci Res 41:291-296. Remyelination is a normal physiological response to myelin damage … central issue in CNS repair in MS is not whether remyelination occurs, but rather can we determine therapies to stimulate myelin repair [my italics …].
Duprez Theirry, Grandin C and Conrad G (1995) Reversal of multiple spinal MS lesions at MRI: An uncommon observation. Acta Neurol (Bel) 95:244-246. This paper illustrates disappearance of numerous spinal lesions while brain lesions increased dramatically. Their literature review found that reversal of lesions in spinal cord reported only once, while reversal of brain lesions commonly observed. Authors question whether disease has different characteristics in the brain and spinal cord! [Perhaps more than two articles should be reviewed.em]
Selye Hans (1964) From Dream to Discovery: On Being a Scientist. McGraw-Hill New York, Toronto, London. Selye’s description of how life events and personal thoughts have influenced his career in research.
Freedman Paul (1950) The Principles of Scientific Research. Public Affairs Press, Washington, D.C. p33.
Freedman Paul (1950) The Principles of Scientific Research, Public Affairs Press, Washington D.C. p33. An initiation into the principles of scientific research that are essential to promotion, rather than hindrance of discovery of facts.