OBJECTIVE: To investigate the activation characteristics of microglia (MG) in the rats striatum with MA-induced neurotoxicity. METHODS: Male Wistar rats were divided randomly into control group (n=24) and experimental group (n=24). The rats of experimental group were injected intraperitoneally with MA (15 mg/kg x 8 injections, at 12 hours interval). The rats of control group were administrated with saline. The tissues of striatum of two rat groups were harvested at 0.5 d, 1 d, 2 d, 3 d, 4 d, 5 d, 6 d and 7 d post initial administrations of MA or saline. The structure changes were observed by transmission electron microscopy and CD-11b immunohistochemistry. The ratio of activated MG was calculated and statistically analyzed. RESULTS: In the control group, the morphological characteristics of the MG showed that the cell bodies were small with slender processes, high electronic density nucleus, and fewer organelles known as the "fork-type". In contrast, the MG in the MA-induced neurotoxicity group displayed larger cell body, shorter cell processes or disappeared, lower electronic density nucleus and rich organelles, resembling "bush-like" or "amoeba-like". The ratio of activated MG in control group was below 0.15 at all timepoints, whereas in the experimental group, the ratio of activated MG increased significantly from day 1 to day 7 (P<0.001). CONCLUSION The continuous MA stimulation of the CNS results in prominent MG activation.
Animals ; Corpus Striatum/pathology* ; Immunohistochemistry ; Male ; Methamphetamine/toxicity* ; Microglia/ultrastructure* ; Microscopy, Electron, Scanning ; Random Allocation ; Rats ; Rats, Wistar ; Staining and Labeling ; Time Factors

OBJECTIVETo investigate lipopolysaccharide (LPS) induced acute cerebral inflammatory damage and the therapeutic effect of ginkgolide B (BN52021).

METHODSThirty 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.

RESULTSThe 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.

CONCLUSIONLPS 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.

Animals ; Behavior, Animal ; drug effects ; Brain Diseases ; chemically induced ; pathology ; prevention & control ; Fibrinolytic Agents ; therapeutic use ; Ginkgolides ; therapeutic use ; Hippocampus ; drug effects ; ultrastructure ; Immunohistochemistry ; Inflammation ; chemically induced ; pathology ; prevention & control ; Lactones ; therapeutic use ; Lipopolysaccharides ; toxicity ; Maze Learning ; drug effects ; Microglia ; metabolism ; Microscopy, Electron, Transmission ; Neurons ; drug effects ; ultrastructure ; Platelet Activating Factor ; drug effects ; metabolism ; Platelet Membrane Glycoproteins ; antagonists & inhibitors ; Rats ; Rats, Sprague-Dawley ; Receptors, G-Protein-Coupled ; antagonists & inhibitors