Cell proliferation and replacement following contusive spinal cord injury.
After spinal cord injury (SCI), about 50% of the oligodendrocytes and astrocytes in the residual white matter at the injury site are lost by 24 h. However, chronically after SCI, the density of oligodendrocytes is normal. Previous studies have shown that the adult rat spinal cord contains a pool of proliferating glial progenitors whose progeny could help restore cell density after injury. To study proliferation in response to injury, we performed SCI on adult female rats at the T8 level, using a standardized contusion model. Animals received bromodeoxyuridine (BrdU) injections during the first week after SCI, and were perfused within 2 h for acute studies, and at 6 weeks for chronic studies. The tissue was analyzed using immunohistochemical detection of BrdU and cell marker antigens. We demonstrate that cell proliferation in the residual white matter is increased at 1-7 days after SCI, peaking on day 3. Dividing cells include oligodendrocytes, astrocytes, microglia/macrophages, and a high proportion of NG2(+) glial precursors. By 6 weeks, some cells that had been labeled 2-4 days after SCI were still present. Double immunohistochemistry showed that while very few of these cells expressed NG2 or the microglia/macrophage marker OX42, about 50% expressed CC1 or glial fibrillary acidic protein (GFAP), markers of mature oligodendrocytes and astrocytes, respectively. The post-injury environment represented by residual white matter is thus permissive to the differentiation of glial precursors. Cells that are stimulated to divide during the first week after SCI develop chronically into mature phenotypes that replace macroglia lost after injury.
Zai
Laila J
LJ
Department of Neuroscience, Georgetown University, Washington, DC 20057, USA.
Wrathall
Jean R
JR
D000818:Animals; D000954:Antigens, Surface / Q000378:metabolism; D001253:Astrocytes / Q000166:cytology / Q000378:metabolism; D015415:Biomarkers; D001973:Bromodeoxyuridine; D002454:Cell Differentiation / Q000502:physiology*; D049109:Cell Proliferation; D004195:Disease Models, Animal; D005260:Female; D007150:Immunohistochemistry; D009413:Nerve Fibers, Myelinated / Q000502:physiology; D009416:Nerve Regeneration / Q000502:physiology*; D009457:Neuroglia / Q000166:cytology / Q000378:metabolism*; D009836:Oligodendroglia / Q000166:cytology / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013119:Spinal Cord Injuries / Q000503:physiopathology*; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism*; D013904:Thoracic Vertebrae
D000954:Antigens, Surface; D015415:Biomarkers; D001973:Bromodeoxyuridine