Myelin Gene Expression after Experimental Contusive Spinal Cord Injury

Abstract

After incomplete traumatic spinal cord injury (SCI), the spared tissue exhibits abnormal myelination that is associated with reduced or blocked axonal conductance. To examine the molecular basis of the abnormal myelination, we used a standardized rat model of incomplete SCI and compared normal uninjured tissue with that after contusion injury. We evaluated expression of mRNA for myelin proteins using in situ hybridization with oligonucleotide probes to proteolipid protein (PLP), the major protein in central myelin; myelin basic protein (MBP), a major component of central myelin and a minor component of peripheral myelin; and protein zero (P0), the major structural protein of peripheral myelin, as well as myelin transcription factor 1 (MYT1). We found reduced expression of PLP and MBP chronically after SCI in the dorsal, lateral, and ventral white matter both rostral and caudal to the injury epicenter. Detailed studies of PLP at 2 months after injury indicated that the density of expressing cells was normal but mRNA per cell was reduced. In addition, P0, normally restricted to the peripheral nervous system, was expressed both at the epicenter and in lesioned areas at least 4 mm rostral and caudal to it. Thus, after SCI, abnormal myelination of residual axons may be caused, at least in part, by changes in the transcriptional regulation of genes for myelin proteins and by altered distribution of myelin-producing cells. In addition, the expression of MYT1 mRNA and protein seemed to be upregulated after SCI in a pattern suggesting the presence of undifferentiated progenitor cells in the chronically injured cord.

No Evidence for Chronic Demyelination in Spared Axons after Spinal Cord Injury in a Mouse

“…B, There is a correlation between increased axon diameter and increased internode length in injured (empty triangles, R 2 ϭ 0.22) and control (black squares, R 2 ϭ 0.12) conditions. (Wrathall et al, 1998) are reduced in the injured spinal cord, these studies suggest myelin may be unstable or insufficiently thick to insulate spared axons. The implications are that chronic demyelination in the absence of axonal loss can contribute to dysfunction of the injured spinal cord.…”

“…Initial demyelination is thought to be caused by necrosis of oligodendrocytes; however, it is not exactly clear what causes prolonged oligodendrocyte death weeks and months after injury (Blight, 1985;Crowe et al, 1997). In accordance with morphological studies of myelin disintegration (Balentine, 1978;Griffiths and McCulloch, 1983), proteolipid protein (PLP) and myelin basic protein (MBP) expression is significantly reduced after injury (Wrathall et al, 1998). In addition, immunohistochemistry studies demonstrate that sodium and potassium channels as well as contactinassociated protein (CASPR) distribution lose their compact and restricted staining pattern in demyelinated fibers (KarimiAbdolrezaee et al, 2004).…”

2,3-Dihydroxy-6-Nitro-7-Sulfamoyl-Benzo(f)Quinoxaline Reduces Glial Loss and Acute White Matter Pathology after Experimental Spinal Cord Contusion

“…Some of the nuclei appeared to be endothelial cells, as indicated by their flattened appearance. The other cells, unidentified with immunohistochemical markers, had physical features similar to glia and may reflect a small population of glia precursor cells present in adult ventromedial WM (Wrathall et al, 1998).…”

“…T wo blocks representative of the injury at each level (epicenter, ϩ1 and Ϫ1 mm) were trimmed to ϳ1 mm 2 of ventromedial W M. Our decision to use ventromedial W M is based on previous studies that showed in our SCI model that this region is consistently intact at 15 min after injury and shows evidence of subsequent secondary injury processes Wrathall, 1985, 1989;Wrathall et al, 1994Wrathall et al, , 1998Rosenberg and Wrathall, 1997;Teng and Wrathall, 1997) that may be reduced with acute therapeutic interventions (Wrathall et al, 1994;Teng and Wrathall, 1997). Thus, the ventromedial region appears to be a suitable area in which to study mechanisms of secondary injury in W M (Rosenberg and Wrathall, 1997).…”

CatSper genes expression, semen characteristics and histology of testes in the contusive spinal cord-injured mice model

“…We surgically induced cord injury in mice, based on the protocol previously described by Wrathall et al 11 Briefly, the mice were anesthetized with Ketamine (90 mg kg…”