Attenuation of astrogliosis by suppressing of microglial proliferation with the cell cycle inhibitor olomoucine in rat spinal cord injury model.
Microglial activation/proliferation and reactive astrogliosis are commonly observed and have been considered to be closely relevant pathological processes during spinal cord injury (SCI). However, the molecular mechanisms underlying this microglial-astroglial interaction are still poorly understood. We showed recently that the continuous injection of the cell cycle inhibitor olomoucine not only markedly suppressed microglial proliferation and associated release of pro-inflammatory cytokines, but also attenuated astroglial scar formation and the lesion cavity and mitigated the functional deficits in rat SCI animal model. In this study, we asked whether microglial activation/proliferation plays an initial role and also necessary in maintaining astrogliosis in SCI model. Our results showed that traumatic induced microglial activation/proliferation precedes astrogliosis, and the up-regulated GFAP expression at both mRNA and protein levels was temporally posterior to the microglial activation. Furthermore, when the cell cycle inhibitor olomoucine was administered only once 1 h post-SCI that should selectively suppress microglial proliferation, the subsequent SCI induced increase in GFAP expression at 1, 2 and 4 weeks was significantly attenuated, suggesting that microglial activation/proliferation played an important role for the later onset astrogliosis after SCI. Consistent with the results that microglial proliferation always precedes astroglial proliferation and there is at present no evidence of other astroglial precursors, which as always does not mean that they will not be uncovered by further searching, and in view of the fact that microglial-derived pro-inflammatory cytokines promote astrogliosis as we reported recently, these findings together suggest that by release of cytokines and other soluble products, the early onset microglial activation/proliferation can significantly influence the subsequent development of reactive astrogliosis and glial scar formation in SCI animal model.
Tian
Dai-shi
DS
Department of Neurology, Affiliated Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430030, PR China.
Dong
Qiang
Q
Pan
Deng-ji
DJ
He
Yi
Y
Yu
Zhi-yuan
ZY
Xie
Min-jie
MJ
Wang
Wei
W
D000704:Analysis of Variance; D000818:Animals; D039481:CD11b Antigen / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects*; D004195:Disease Models, Animal; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D005904:Glial Fibrillary Acidic Protein / Q000235:genetics / Q000378:metabolism; D005911:Gliosis / Q000188:drug therapy* / Q000209:etiology; D019394:Ki-67 Antigen / Q000378:metabolism; D007701:Kinetin / Q000627:therapeutic use*; D017628:Microglia / Q000187:drug effects*; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D013119:Spinal Cord Injuries / Q000150:complications / Q000188:drug therapy* / Q000473:pathology*; D013997:Time Factors
D039481:CD11b Antigen; D004791:Enzyme Inhibitors; D005904:Glial Fibrillary Acidic Protein; D019394:Ki-67 Antigen; D012333:RNA, Messenger; C090046:olomoucine; D007701:Kinetin