title: Cell cycle inhibition attenuates microglia induced inflammatory response and alleviates neuronal cell death after spinal cord injury in rats.
abstract: The spinal cord is well known to undergo inflammatory reactions in response to traumatic injury. Activation and proliferation of microglial cells, with associated proinflammatory cytokines expression, plays an important role in the secondary damage following spinal cord injury. It is likely that microglial cells are at the center of injury cascade and are targets for treatments of CNS traumatic diseases. Recently, we have demonstrated that the cell cycle inhibitor olomoucine attenuates astroglial proliferation and glial scar formation, decreases lesion cavity and mitigates functional deficits after spinal cord injury (SCI) in rats [Tian, D.S., Yu, Z.Y., Xie, M.J., Bu, B.T., Witte, O.W., Wang, W., 2006. Suppression of astroglial scar formation and enhanced axonal regeneration associated with functional recovery in a spinal cord injury rat model by the cell cycle inhibitor olomoucine. J. Neurosci. Res. 84, 1053-1063]. Whether neuroprotective effects of cell cycle inhibition are involved in attenuation of microglial induced inflammation awaits to be elucidated. In the present study, we sought to determine the influence of olomoucine on microglial proliferation with associated inflammatory response after spinal cord injury. Tissue edema formation, microglial response and neuronal cell death were quantified in rats subjected to spinal cord hemisection. Microglial proliferation and neuronal apoptosis were observed by immunofluorescence. Level of the proinflammatory cytokine interleukin-1beta (IL-1beta) expression in the injured cord was determined by Western blot analysis. Our results showed that the cell cycle inhibitor olomoucine, administered at 1 h post injury, significantly suppressed microglial proliferation and produced a remarkable reduction of tissue edema formation. In the olomoucine-treated group, a significant reduction of activated and/or proliferated microglial induced IL-1beta expression was observed 24 h after SCI. Moreover, olomoucine evidently attenuated the number of apoptotic neurons after SCI. Our findings suggest that modulation of microglial proliferation with associated proinflammatory cytokine expression may be a mechanism of cell cycle inhibition-mediated neuroprotections in the CNS trauma.
authors.affiliation: Department of Neurology, Affiliated Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430030, PR China.
authors.forename: Dai-shi
authors.initials: DS
authors.lastname: Tian
authors.forename: Min-jie
authors.initials: MJ
authors.lastname: Xie
authors.forename: Zhi-yuan
authors.initials: ZY
authors.lastname: Yu
authors.forename: Qiang
authors.initials: Q
authors.lastname: Zhang
authors.forename: Yi-hui
authors.initials: YH
authors.lastname: Wang
authors.forename: Bin
authors.initials: B
authors.lastname: Chen
authors.forename: Chen
authors.initials: C
authors.lastname: Chen
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001929:Brain Edema / Q000188:drug therapy / Q000209:etiology / Q000473:pathology; D039481:CD11b Antigen / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects / Q000502:physiology*; D016923:Cell Death; D049109:Cell Proliferation / Q000187:drug effects; D016207:Cytokines / Q000378:metabolism; D053938:DNA Fragmentation; D004195:Disease Models, Animal; D004791:Enzyme Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D005260:Female; D007150:Immunohistochemistry / Q000379:methods; D019394:Ki-67 Antigen / Q000378:metabolism; D007701:Kinetin / Q000494:pharmacology / Q000627:therapeutic use; D017628:Microglia / Q000473:pathology*; D009474:Neurons / Q000473:pathology*; D010751:Phosphopyruvate Hydratase / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013119:Spinal Cord Injuries / Q000150:complications* / Q000473:pathology*
chemical_list: D039481:CD11b Antigen; D016207:Cytokines; D004791:Enzyme Inhibitors; D019394:Ki-67 Antigen; C090046:olomoucine; D010751:Phosphopyruvate Hydratase; D007701:Kinetin