High-dose corticosteroids after spinal cord injury reduce neural progenitor cell proliferation.
We assessed whether a clinical dose of the anti-inflammatory drug methylprednisolone (MP) given to adult mice acutely after spinal cord injury (SCI) influences spinal cord or hippocampal progenitor cells. Mice underwent a thoracic dorsal hemisection of the spinal cord and received 30 mg/kg MP immediately and 24 h post-lesion. 5-Bromo-2-deoxyuridine (BrdU) was administered after lesion either acutely (1-6 days) or late (22-27 days) to label proliferating cells. Reaction of microglia/macrophages was quantified 7 days post-lesion and proliferation as well as differentiation of neural progenitor cells (NPCs) was analyzed after two survival times (7 days and 28 days). We also tested the influence of MP on microglia and adult NPCs in vitro. MP treatment reduced the number of cells proliferating acutely after SCI in the spinal cord and hippocampus. Besides reducing activation and proliferation of microglia/macrophages in the spinal cord, MP also decreased the number of oligodendrocyte progenitor cells (OPCs). Analysis of acutely BrdU-labeled cells at 28 days post-lesion suggests that proliferation and number of OPCs were changed chronically. Late proliferating cells were no longer influenced by the glucocorticoid regimen. In vitro experiments showed an inhibitory effect of MP on adult spinal cord and hippocampal progenitor cell proliferation. Both cell types express the glucocorticoid and mineralocorticoid receptors allowing a direct effect of MP. Our results show that MP reduces OPC proliferation after SCI either by affecting progenitor cells directly or via its anti-inflammatory effects. These findings open the question to which extent MP treatment limits the repair capacity of endogenous progenitor cells after CNS injury.
Brain Research Institute, University of Zurich, Zurich, Switzerland.
A
A
Schröter
R M
RM
Lustenberger
F J
FJ
Obermair
M
M
Thallmair
D053687:Adult Stem Cells / Q000187:drug effects* / Q000502:physiology; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000009:adverse effects*; D001973:Bromodeoxyuridine; D002452:Cell Count; D049109:Cell Proliferation / Q000187:drug effects*; D005260:Female; D005938:Glucocorticoids / Q000009:adverse effects; D006624:Hippocampus / Q000187:drug effects / Q000503:physiopathology; D008264:Macrophages / Q000187:drug effects / Q000502:physiology; D008775:Methylprednisolone / Q000009:adverse effects*; D051379:Mice; D008810:Mice, Inbred C57BL; D017628:Microglia / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000187:drug effects* / Q000502:physiology; D009836:Oligodendroglia / Q000187:drug effects / Q000502:physiology; D013116:Spinal Cord / Q000187:drug effects / Q000503:physiopathology; D013119:Spinal Cord Injuries / Q000503:physiopathology*; D013997:Time Factors
D000893:Anti-Inflammatory Agents; D005938:Glucocorticoids; D001973:Bromodeoxyuridine; D008775:Methylprednisolone