Spinal cord injury (SCI) causes delayed secondary biochemical alterations that lead to tissue loss and associated neurological dysfunction. Up-regulation of cell cycle proteins occurs in both neurons and glia after SCI and may contribute to these changes. The present study examined the role of cell cycle activation on secondary injury after severe SCI in rat. SCI caused cell cycle protein up-regulation associated with neuronal and oligodendroglial apoptosis, glial scar formation and microglial activation. Treatment with the cell cycle inhibitor flavopiridol reduced cell cycle protein induction and significantly improved functional recovery versus vehicle-treated controls at 21 and 28 days post-injury. Treatment also significantly reduced lesion volume, as measured by MRI and histology, decreased astrocytic reactivity, attenuated neuronal and oligodendroglial apoptosis and reduced the production of factors associated with microglial activation. Thus, flavopiridol treatment improves outcome after SCI by inhibiting cell cycle pathways, resulting in beneficial multifactorial actions on neurons and glia.
机构:
Georgetown Univ, Med Ctr, Dept Neurosci, Lab Study CNS Injury, Washington, DC 20057 USAGeorgetown Univ, Med Ctr, Dept Neurosci, Lab Study CNS Injury, Washington, DC 20057 USA
Cernak, I
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Stoica, B
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Byrnes, KR
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机构:
Georgetown Univ, Med Ctr, Dept Neurosci, Lab Study CNS Injury, Washington, DC 20057 USAGeorgetown Univ, Med Ctr, Dept Neurosci, Lab Study CNS Injury, Washington, DC 20057 USA
Byrnes, KR
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Di Giovanni, S
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Georgetown Univ, Med Ctr, Dept Neurosci, Lab Study CNS Injury, Washington, DC 20057 USAGeorgetown Univ, Med Ctr, Dept Neurosci, Lab Study CNS Injury, Washington, DC 20057 USA
Di Giovanni, S
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Faden, AI
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机构:
Georgetown Univ, Med Ctr, Dept Neurosci, Lab Study CNS Injury, Washington, DC 20057 USAGeorgetown Univ, Med Ctr, Dept Neurosci, Lab Study CNS Injury, Washington, DC 20057 USA
机构:
Georgetown Univ, Med Ctr, Dept Neurosci, Lab Study CNS Injury, Washington, DC 20057 USAGeorgetown Univ, Med Ctr, Dept Neurosci, Lab Study CNS Injury, Washington, DC 20057 USA
Cernak, I
;
论文数: 引用数:
h-index:
机构:
Stoica, B
;
Byrnes, KR
论文数: 0引用数: 0
h-index: 0
机构:
Georgetown Univ, Med Ctr, Dept Neurosci, Lab Study CNS Injury, Washington, DC 20057 USAGeorgetown Univ, Med Ctr, Dept Neurosci, Lab Study CNS Injury, Washington, DC 20057 USA
Byrnes, KR
;
Di Giovanni, S
论文数: 0引用数: 0
h-index: 0
机构:
Georgetown Univ, Med Ctr, Dept Neurosci, Lab Study CNS Injury, Washington, DC 20057 USAGeorgetown Univ, Med Ctr, Dept Neurosci, Lab Study CNS Injury, Washington, DC 20057 USA
Di Giovanni, S
;
Faden, AI
论文数: 0引用数: 0
h-index: 0
机构:
Georgetown Univ, Med Ctr, Dept Neurosci, Lab Study CNS Injury, Washington, DC 20057 USAGeorgetown Univ, Med Ctr, Dept Neurosci, Lab Study CNS Injury, Washington, DC 20057 USA