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