Glial cell loss, proliferation and replacement in the contused murine spinal cord.
Studies in the rat have shown that contusive spinal cord injury (SCI) results in devastating pathology, including significant loss of mature oligodendrocytes and astrocytes even in spared white matter. Subsequently, there is increased proliferation of endogenous NG2(+) cells, postulated to contribute to replacement of mature glia chronically, which is important for functional recovery. Studies of mechanisms that stimulate endogenous progenitor cells would be facilitated by using mouse models with naturally occurring and genetically engineered mutations. To determine whether the murine response is similar to that in the rat, we performed contusive SCI on adult female C57Bl/6 mice at the T8-9 level. Animals received bromodeoxyuridine injections in the first week following injury and were killed at 1, 3, 4, 7 or 28 days postinjury (DPI). The overall loss of macroglia and the temporal-spatial response of NG2(+) cells after SCI in the (C57Bl/6) mouse was very similar to that in the (Sprague-Dawley) rat. By 24 h after SCI nearly half of the macroglia in spared ventral white matter had been lost. Cell proliferation was increased at 1-7 DPI, peaking at 3-4 DPI. Dividing cells included NG2(+) cells and Cd11b(+) macrophages and microglia. Furthermore, cells dividing in the first week expressed markers of mature glia at 28 DPI. The similarities in endogenous progenitor cell response to SCI in the mouse and rat suggest that this is a fundamental injury response, and that transgenic mouse models may be used to further probe how this cellular response to SCI might be enhanced to improve recovery after SCI.
Lytle
Judith M
JM
Department of Neuroscience, Georgetown University, The Research Building, Washington DC 20007, USA.
Wrathall
Jean R
JR
D000818:Animals; D000941:Antigens / Q000378:metabolism; D001522:Behavior, Animal; D001973:Bromodeoxyuridine; D039481:CD11b Antigen / Q000378:metabolism; D002452:Cell Count / Q000379:methods; D049109:Cell Proliferation; D005260:Female; D051379:Mice; D008810:Mice, Inbred C57BL; D009043:Motor Activity / Q000502:physiology; D009457:Neuroglia / Q000502:physiology*; D011509:Proteoglycans / Q000378:metabolism; D020127:Recovery of Function / Q000502:physiology*; D013119:Spinal Cord Injuries / Q000473:pathology* / Q000503:physiopathology*; D013997:Time Factors; D000099216:Chondroitin Sulfate Proteoglycan 4
D000941:Antigens; D001973:Bromodeoxyuridine; D039481:CD11b Antigen; D011509:Proteoglycans; D000099216:Chondroitin Sulfate Proteoglycan 4