The expression of Cyclins in neurons of rats after focal cerebral ischemia

Abstract

The change of the expression of Cyclins in neurons of rats after focal cerebral ischemia was investigated. Ischemia was induced by temporary middle cerebral artery occlusion (MCAO). The experimental rats induced by MCAO were sacrificed on 7th and 14th day after reperfusion. The brain was taken out at 7th and 14th day after injury, and the expression of Cyclin D₁, E, A and B₁ in neurons of cerebral cortex or hippocampal CA1 region was detected by immunofluorescence and confocal microscope. The results showed that after MCAO, in the ipsilateral CA1 subfield of hippocampus the expression of Cyclin D₁, E, A and B1 in neurons was significantly gradually up-regulated at 7th and 14th day after reperfusion (P<0.05) as compared with that in control group. In the ipsilateral cerebral cortex the expression of Cyclin D₁ and B₁ in neurons was notably gradually down-regulated at 7th and 14th day, and that of Cyclin E and A was significantly up-regulated at 14th day after reperfusion as compared with that in control group (all P<0.05). It was concluded that there was a differential sensitivity among neurons from different brain regions to ischemic injury. But all of them re-enter into cell cycle after MCAO.

Keywords

cerebral ischemia / neuron / cell cycle / confocal microscope

References

[1] RashidianJ., IyirhiaroG., AleyasinH., et al.. Multiple cyclin-dependent kinases signals are critical mediators of ischemia/hypoxic neuronal death in vitro and in vivo. Proc Natl Acad Sci U S A, 2005, 102(39): 14 080-14 085

[2] TakanoK., TatlisumakT., BergmannA. G., et al.. Reproducibility and reliability of middle cerebral artery occlusion using a silicone-coated suture (Koizumi) in rats. J Neurol Sci, 1997, 153(1): 8-11

[3] BedersonJ. B., PittsL. H., TsujiM., et al.. Rat middle cerebral artery occlusion: evaluation of the model and development of a neurologic examination. Stroke, 1986, 17(3): 472-476

[4] SchwartzE. I., SmilenovL. B., PriceM. A., et al.. Cell cycle activation in postmitotic neurons is essential for DNA repair. Cell Cycle, 2007, 6(3): 318-329

[5] HuntT., LucaF. C., RudermanJ.. The requirements for protein synthesis and degradation, and the control of destruction of Cyclins A and B in the meiotic and mitotic cell cycles of the clam embryo. J Cell Biol, 1992, 116(3): 707-724

[6] SchmetsdorfS., GartnerU., ArendtT.. Expression of cell cycle-related proteins in developing and adult mouse hippocampus. Int J Devl Neuroscience, 2005, 23(1): 101-112

[7] TimsitS., RiveraS., OuaghiP., et al.. Increased cyclinD1 in vulnerable neurons in the hippocampus after ischemia and epilepsy: a modulator of in vivo programmed cell death?. Eur J Neurosci, 1999, 11(1): 263-278

[8] KatchanovJ., HarmsC., GertzK., et al.. Mild cerebral ischemia induces loss of cyclin-dependent kinase inhibitors and activation of cell cycle machinery before delayed neuronal cell death. J Neurosci, 2001, 21(14): 5045-5053

[9] OsugaH., OsugaS., WangF., et al.. Cyclin-dependent kinases as a therapeutic target for stroke. Proc Natl Acad Sci U S A, 2000, 97(18): 10 254-10 259

[10] WangF., CorbettD., OsugaH., et al.. Inhibition of cyclin-dependent kinases improves CA1 neuronal survival and behavioral performance after global ischemia in the rat. J Cereb Blood Flow Metab, 2002, 22(2): 171-182

[11] BeckerE. B., BonniA.. Cell cycle regulation of neuronal apoptosis in development and disease. Prog Neurobiol, 2004, 72(1): 1-25

[12] IboljaC., BogdanS. T., KimberlyR. B., et al.. Role of the cell cycle in the pathobiology of central nervous system trauma. Cell Cycle, 2005, 4(9): 89-96