Elsevier

Brain Research

Volume 782, Issues 1–2, 26 January 1998, Pages 126-135
Brain Research

Research report
Spontaneous long-term remyelination after traumatic spinal cord injury in rats

https://doi.org/10.1016/S0006-8993(97)01252-3Get rights and content

Abstract

The capability of the central nervous system to remyelinate axons after a lesion has been well documented, even though it had been described as an abortive and incomplete process. At present there are no long- term morphometric studies to assess the spinal cord (SC) remyelinative capability. With the purpose to understand this phenomenon better, the SC of seven lesionless rats and the SC of 21 rats subjected to a severe weight-drop contusion injury were evaluated at 1, 2, 4, 6, and 12 months after injury. The axonal diameter and the myelination index (MI=axolemmal perimeter divided by myelinated fiber perimeter) were registered in the outer rim of the cord at T9 SC level using a transmission electron microscope and a digitizing computer system. The average myelinated fiber loss was 95.1%. One month after the SC, 64% of the surviving fibers were demyelinated while 12 months later, only 30% of the fibers had no myelin sheath. The MI in the control group was 0.72±0.07 (X±S.D.). In the experimental groups, the greatest demyelination was observed two months after the lesion (MI=0.90±0.03), while the greatest myelination was observed 12 months after the injury (MI=0.83±0.02). There was a statistical difference (p<0.02) in MI between 2 and 12 months which means that remyelination had taken place. Remyelination was mainly achieved because of Schwann cells. The proportion of small fibers (diameter=0.5 μm or less) considered as axon collaterals, increased from 18.45% at 1 month to 27.66% a year after the contusion. Results suggest that remyelination is not an abortive phenomenon but in fact a slow process occurring parallel to other tissue plastic phenomena, such as the emission of axon collaterals.

Introduction

Mechanical trauma to the spinal cord (SC) produces axonal destruction and extensive demyelination by damaging, not only axons, but also oligodendrocytes and astrocytes 8, 9, 26. As a result, axons that survive the injury lose their myelin sheath and cannot be remyelinated, while axons or collaterals, resulting from the plastic mechanisms of the SC, are not myelinated 8, 9, 21, 61.

Myelin is essential for normal nervous system function [57]so, loss of the axon myelin sheath has important repercussions on nerve physiology as may be a decrease in conduction velocity or overt nerve conduction block that may play a major role in the neurological deficits after SC injury [61]. As a consequence, functional recovery of this pathology depends at least in part on nervous system remyelinating ability 40, 44, 60, 61.

Research over the past several decades has demonstrated that myelin repair in the central nervous system (CNS) is a normal physiological response to myelin injury 13, 38, 49. However, some authors regard remyelination in this system as an abortive and incomplete phenomenon 3, 5, 6, 11, 18, 25, 31, 32, 33, 39, 47, 48, 56.

The availability of numerous models of CNS demyelination amenable to experimental manipulation 20, 30, 37, 41, 45, 54, 62has allowed a broad range of approaches to develop and for evaluating therapies designed to promote CNS remyelination 19, 42, 43, 44, 45, 55. However, with the aim to design rational therapeutic strategies in different pathologic processes related to SC injuries, it is necessary to clearly understand the spontaneous plastic mechanisms subjacent in each one of those processes and not to negatively interfere with them.

The long-term morphometric effect on the axon diameters and axonal myelination of the adult rat SC fibers after an experimental weight-drop contusion injury was analyzed in order to better understand the CNS remyelinative capacity and knowing whether remyelination constitutes an abortive and incomplete process in the biology of the SC.

Section snippets

Surgery and post-surgical care

Twenty-eight Long-Evans female rats 14 to 16 weeks of age, weighing 240 to 260 g, were anesthetized with an intramuscular (IM) mixture of ketamine (77.5 mg/kg bw) and xylacine (12.5 mg/kg bw). Benzatin penicillin (240,000 units) was administered IM, as a single dose, once the rat was anesthetized.

The protocol was accepted by the hospital's Ethics Committee while considering the proper handling, housing, surgical and postsurgical care of the animals. Under aseptic conditions, each rat was

Number of axons and axon diameter

One month after the SCC, the average loss of myelinated fibers studied in this experimental severe lesion model was 95.1%. In other words, only 4.9% of the fivers survived. Twelve months after the lesion, the population grew somewhat to 6.3%.

In the control group the axon diameter distribution was unimodal. Small-diameter axons, 0.5 μm or less, represented a minority of 1.08%. There were few axons (3.5%) with 5.1 μm or more in diameter. Many caliber axons (31.57%) were between 2.1 and 5 μm and

Discussion

The reasons for the remyelinative relative failure in the CNS are poorly understood and this makes it difficult to develop experimental strategies to promote efficient remyelination in the SC. In the present study, the results obtained show the time course for plastic and remyelinative SC capabilities. These could be useful for understanding the moment at which different therapeutic strategies can be used after a severe SCC injury without any interference or blockage of the spontaneous

Acknowledgements

The authors wish to thank Armando Zepeda, Elena Oliva, Adrian Rondan, Silvia Antuna and Gerardo Torres for their help with the electron microscope, Manuel Pérez for his help with computational programs and Tomás Cruz and Mario Garcı́a for their photographic work. Hermelinda Salgado-Ceballos holds a scholarship from The National Council of Science and Technology (CONACYT), contract number 80959.

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