Immunological suppression of central nervous system (CNS) myelin and the effect of myelin suppression on CNS repair after injury

• Main Author: Keirstead, Hans Stegmann
• Language: English
• Published: 2009
• Online Access: http://hdl.handle.net/2429/7088

In higher vertebrates, axons within the differentiated central nervous system (CNS) possess a very limited capacity for repair after injury. The following experiments were designed to determine the contributions of CNS myelin to the lack of regeneration observed following transection of the late embryonic and hatchling chick spinal cord. The developmental onset of myelination in the chick begins at embryonic day (E) 13 of the 21 day developmental period. Spinal cord transections after the developmental onset of myelination result in little or no neuroanatomical repair or functional recovery. However, intraspinal injection of complement-binding galactocerebroside (GalC) antibodies or 04 antibodies (which react with sulfatide, seminolipid and an unidentified antigen on oligodendrocyte progenitors) plus complement between E9-E12 results in a delay in the onset of myelination until E17 (developmental myelin-suppression). A subsequent transection of the spinal cord as late as El 5 (i.e. during the normal restrictive period for repair) results in complete neuroanatomical regeneration and functional recovery. Spinal cord transections on El5 in a normally-myelinated embryo result in no neuroanatomical regeneration or functional recovery. These findings indicate that CNS myelin is inhibitory to the functional regeneration of transected spinal cord in embryonic chick (Keirstead et al. 1992). These studies also suggest that myelin suppression might also facilitate regeneration after adult spinal cord injury. Hatchling chickens are precocial and their brainstem and spinal cord can be considered in all respects adult-like. Administration of complement-binding GaIC antibodies or 04 antibodies plus complement to the hatchling spinal cord results in the transient removal of spinal cord myelin (immunological demyelination). The thoracic cord of posthatching day (P)2-P10 chickens were completely transected and immunological demyelination was simultaneously initiated. Fourteen to 28 days later, retrograde tract tracing, including double-labeling studies, indicated that approximately 5-15% of the brainstem-spinal projections had regenerated across the transection site to lumbar levels. Even though voluntary locomotion was not observed after recovery, focal electrical stimulation of identified brainstem locomotor regions evoked either stepping movements or ‘fictive’ stepping in paralysed animals (collaborative studies, see chapter 5). This indicates that the transient demyelination of injured hatchling (i.e. mature) chick spinal cord facilitated axonal regeneration resulting in some functional synaptogenesis with spinal neurons.