Lipopolysaccharide-induced cerebral inflammatory damage and the therapeutic effect of platelet activating factor receptor antagonist.
OBJECTIVE
To investigate lipopolysaccharide (LPS) induced acute cerebral inflammatory damage and the therapeutic effect of ginkgolide B (BN52021).


METHODS
Thirty Sprague-Dawley rats were randomly divided into 3 groups (n = 10 for each group): Control group, Model group and Treatment group (treated with BN52021). LPS were injected into the fourth ventricle of rat to make a neuroinflammatory murine model. Morris water maze was used to detect the learning and memory ability of rats; changes of synapse number and subcellular ultrastructures were observed under a transmission electron microscope; OX-42 positive microglia in the brain was detected by immunohistochemical method.


RESULTS
The average escape latency in the Treatment group were significantly shortened than that in the Model group; and the percentage of swimming distance traveled in platform quadrant accounting for total distance increased markedly. The rough endoplasmic reticulum and polyribosomes in the Treatment group were more than that in the Model group, but the number of synapses seemed to have no obvious change. The number of OX-42 positive microglia in the Treatment group decreased markedly than that in the Model group, and the grey density of OX-42-positive cells increased significantly.


CONCLUSIONS
LPS can induce inflammatory damages to the brain, but the damage could be antagonized by BN52021. Platelet activating factor receptor antagonist may offer an effective therapy for neurodegeneration diseases.
Liu
Wen-Chao
WC
Department of Anatomy, Medical College of Shanghai Jiaotong University, Shanghai 200025, China.
Ding
Wen-Long
WL
Gu
Hong-Yu
HY
Chen
Ming-Feng
MF
Hu
Jin-Jia
JJ
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001927:Brain Diseases / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D005343:Fibrinolytic Agents / Q000627:therapeutic use; D046934:Ginkgolides / Q000627:therapeutic use*; D006624:Hippocampus / Q000187:drug effects / Q000648:ultrastructure; D007150:Immunohistochemistry; D007249:Inflammation / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control; D007783:Lactones / Q000627:therapeutic use*; D008070:Lipopolysaccharides / Q000633:toxicity*; D018782:Maze Learning / Q000187:drug effects; D017628:Microglia / Q000378:metabolism; D046529:Microscopy, Electron, Transmission; D009474:Neurons / Q000187:drug effects / Q000648:ultrastructure; D010972:Platelet Activating Factor / Q000187:drug effects / Q000378:metabolism; D010980:Platelet Membrane Glycoproteins / Q000037:antagonists & inhibitors*; D051381:Rats; D017207:Rats, Sprague-Dawley; D043562:Receptors, G-Protein-Coupled / Q000037:antagonists & inhibitors*
D005343:Fibrinolytic Agents; D046934:Ginkgolides; D007783:Lactones; D008070:Lipopolysaccharides; D010972:Platelet Activating Factor; D010980:Platelet Membrane Glycoproteins; D043562:Receptors, G-Protein-Coupled; C039351:platelet activating factor receptor; C045856:ginkgolide B