Effect Of Cell Cycle Regulation On Proliferation And Activation Of Astrocytes And Induced Neuro-protection In Pentylenetrazol Induced Chronic Epileptic Rats

Abstract Object:To study the effect of Cyclin-dependent protein kinases selective inhibitor olomoucine on the activation and proliferation and of AST,and on astrocytic apoptosis and on neuronal apoptosis in pentylenetrazol induced chronic epileptic rats.to explore the effect of cell cycle regulation on chronic epilepsy.Methods: The chronic epileptic model was induced by Pentylenetetrazol ( PTZ ) .Rats were randomly divided into 3 groups:sham-operated control groups(are treated by physiological saline);PTZ group and Olomoucine+PTZ group.The experimental rats were sacrificed on day 1,3,7,21,30,and 49 after complete kindling.The brain was taken, and then the apoptosis of neurons and astrocytes was detected by terminal deoxynucleotidyl transferase mediated dUTP nick end labeling (TUNEL).The expression of NeuN and GFAP were observed by immunofluorescence staining.To observed the dynamic change of GFAP,neuronal apoptosis,astrocytic apoptosis in cortical or hippocampus after treated with Olomoucine - a selective CDK inhibitor.Result:1.After kindling, As a response to"brain injury", AST in cortical and hippocampus area appeared hypertrophy,proliferation,the number Of the GFAP-positive cells increased. After treated with Olomoucine,the hypertrophy proliferation of AST mitigated;the number of the GFAP-positive cells decreased. 2.After kindling,the number of TUNEL-positive astrocytes in cortical or hippocampus significantly increased , After treated with Olomoucine , the number of TUNEL-positive astrocytes in cortical or hippocampus partly decreased.3.After kindling,in the PTZ groups,the number of TUNEL-positive neurons in cortex or hippocampus prominent increased compared with that of the control group(p<0.01). Compared with PTZ groups,the number of TUNEL-positive neurons decreased significantly in Olomoucine+PTZ groups(p<0.05).In Olomoucine+PTZ groups, the number of TUNEL-positive neurons increased significantly in the early period (1,3,7d), notablely on day 1(p<0.01) ,but shows little difference in the later phase( 21,30,49d,p>0.05),compared with that of the control group. 4.Cell cycle inhibitor olomoucine can not prevent the chronic epilepsia model was complete kindling.In the early period,the chronic epilepsia rats were easily kindled after treated with Olomoucine.Conclusion:After kindling, AST entered cell cycle and appeared proliferation and activation, and astrocytic apoptosis increased, neuronal apoptosis increased prominently as well.Olomoucine, a selective CDK inhibitor could inhibit the hypertrophy, activation and proliferation of astrocytes effectively through regulating cell cycle. Our results also suggest that cell cycle regulation can reduce astrocytic and neuronal apoptosis after kindling . which might provide a new target for neuroprotection during chronic epilepsy.