Calcium-mediated paired pulse depression in juvenile rat dorsal striatum

As the major division of the basal ganglia, neostriatum forms mutual connections with multiple brain areas and is critically involved in motor control and learning/memory. Long-term synaptic plasticity has been widely studied in different species recently. However, there are rare reports about the short-term synaptic plasticity in neostratium. In the present study, using field excitatory postsynaptic potentials recording, we reported one form of short-term synaptic plasticity that is paired pulse depression in juvenile rat dorsal striatum slices induced by stimuli of the white matter. The field excitatory postsynaptic potentials could be abolished by α-amino-3-hydroxy-5-methylizoxazole-4-propionic acid receptor antagonist, 6-cyano-7-nitroquinoxaline-2,3-dione, but not by gamma-aminobutyric acid type A receptor antagonist bicuculline or dopamine D1 receptor antagonist SKF-81297. The paired pulse depression in the corticostratial pathway was different from paired pulse facilitation in the hippocampal CA1 synapse. In addition, the paired pulse depression was not affected by bath application of gamma-aminobutyric acid type A receptor antagonist or dopamine D1 receptor antagonist. However, low calcium and high magnesium could attenuate the paired pulse depression. These findings suggest a more complicated plasticity form in the dorsal striatum of juvenile rats that is different from that in the hippocampus, which is related with extracellular calcium.

Effects of Naotan Pill on repair of neural cells and cognitive disorders in juvenile rats following hypoxia and ischemia

BACKGROUND： Hypoxia and ischemia induce neuronal damage, decreased neuronal numbers and synaptophysin levels, and deficits in learning and memory functions. Previous studies have shown that lycium barbarum polysaccharide, the most effective component of barbary wolfberry fruit, has protective effects on neural cells in hypoxia-ischemia. OBJECTIVE： To investigate the effects of Naotan Pill on glutamate-treated neural cells and on cognitive function in juvenile rats following hypoxia-ischemia. DESIGN, TIME AND SETTING： The randomized, controlled, in vivo study was performed at the Cell Laboratory of Lanzhou University, Lanzhou Institute of Modern Physics of Chinese Academy of Sciences, and Department of Traditional Chinese Medicine of Gansu Provincial Rehabilitation Center Hospital, China from December 2005 to August 2006. The cellular neurobiology, in vitro experiment was conducted at the Institute of Human Anatomy, Histology, Embryology and Neuroscience, School of Basic Medical Sciences, Lanzhou University, and Department of Traditional Chinese Medicine of Gansu Provincial Rehabilitation Center Hospital, China from March 2007 to January 2008. MATERIALS： Naotan Pill, composed of barbary wolfberry fruit, danshen root, grassleaf sweetflag rhizome, and glossy privet fruit, was prepared by Gansu Provincial Rehabilitation Center, China. Rabbit anti-synaptophysin, choline acetyl transferase polyclonal antibody, streptavidin-biotin complex kit and diaminobenzidine kit （Boster, Wuhan, China）, as well as glutamate （Hualian, Shanghai, China） were used in this study. METHODS： Cortical neural cells were isolated from neonatal Wistar rats. Neural cell damage models were induced using glutamate, and administered Naotan Pill prior to and following damage. A total of 54 juvenile Wistar rats were equally and randomly assigned into model, Naotan Pill, and sham operation groups. The left common carotid artery was ligated, and then rat models of hypoxic-ischemic injury were assigned to the model and Naotan Pill groups. At 2 days following model induction, rats in the Naotan Pill group were administered Naotan Pillsuspension for 21 days. In the model and sham operation groups, rats received an equal volume of saline. MAIN OUTCOME MEASURES： Neural cell morphology was observed using an inverted phase contrast microscope. Survival rate of neural cells was measured by MTT assay. Synaptophysin and choline acetyl transferase expression was observed in the hippocampal CA1 region of juvenile rats using immunohistochemistry. Cognitive function was tested by the Morris water maze. RESULTS： Pathological changes were detected in glutamate-treated neural cells. Neural cell morphology remained normal after Naotan Pill intervention. Absorbance and survival rate of neural cells were significantly greater following Naotan Pill intervention, compared to glutamate-treated neural cells （P 〈 0.05）. Synaptophysin and choline acetyl transferase expression was lowest in the hippocampal CA1 region in the model group and highest in the sham operation group. Significant differences among groups were observed （P 〈 0.05）. Escape latency and swimming distance were significantly longer in the model group compared to the Naotan Pill group （P 〈 0.05）. CONCLUSION： Naotan Pill exhibited protective and repair effects on glutamate-treated neural cells. Naotan Pill upregulated synaptophysin and choline acetyl transferase expression in the hippocampus and improved cognitive function in rats following hypoxia-ischemia.

Preliminary exploration of animal models of congenital choledochal cysts

BACKGROUND Various animal models have been used to explore the pathogenesis of choledochal cysts(CCs),but with little convincing results.Current surgical techniques can achieve satisfactory outcomes for treatment of CCs.Consequently,recent studies have focused more on clinical issues rather than basic research.Therefore,we need appropriate animal models to further basic research.AIM To establish an appropriate animal model that may contribute to the investigation of the pathogenesis of CCs.METHODS Eighty-four specific pathogen-free female Sprague-Dawley rats were randomly allocated to a surgical group,sham surgical group,or control group.A rat model of CC was established by partial ligation of the bile duct.The reliability of the model was confirmed by measurements of serum biochemical indices,morpho-logy of common bile ducts of the rats as well as molecular biology experiments in rat and human tissues.RESULTS Dilation classified as mild(diameter,≥1 mm to<3 mm),moderate(≥3 mm to<10 mm),and severe(≥10 mm)was observed in 17,17,and 2 rats in the surgical group,respectively,while no dilation was observed in the control and sham surgical groups.Serum levels of alanine aminotransferase,aspartate aminotrans-ferase,total bilirubin,direct bilirubin,and total bile acids were significantly elevated in the surgical group as compared to the control group 7 d after surgery,while direct bilirubin,total bilirubin,and gamma-glutamyltransferase were further increased 14 d after surgery.Most of the biochemical indices gradually decreased to normal ranges 28 d after surgery.The protein expression trend of signal transducer and activator of transcription 3 in rat model was consistent with the human CC tissues.CONCLUSION The model of partial ligation of the bile duct of juvenile rats could morphologically simulate the cystic or fusiform CC,which may contribute to investigating the pathogenesis of CC.

Comparative pharmacokinetics of baicalin and geniposide in juvenile and adult rats after oral administration of Qingkailing Granules

Objective:To explore the effect of age on Qingkailing Granules disposition by comparing the pharmacoknetics of geniposide and baicalin in juvenile and adult rats.Methods:A simple and rapid LC-MS/MS method was developed and validated to simultaneously determine geniposide and baicalin in rat plasma after a simple protein precipitation.The analytes were separated on an Agilent ZORBAX Extend-C18 column.The mobile phase consisted of acetonitrile and water with 0.1%(volume percent)formic acid at a flow rate of 0.6 mL/min.The ionization was conducted using an ESI source in negative ion mode.Multiple reaction monitoring was used for quantification at transitions of m/z 445.0→m/z 268.9 for baicalin,m/z 433.2→m/z 225.0 for geniposide,m/z 431.0→m/z341.0 for vitexin(IS).Juvenile and adult rats were administrated Qingkailing Granules(3 g/kg)orally.Plasma concentrations of baicalin and geniposide were determined by LC-MS/MS.Results:The linear ranges of the analytes were 1-1000 ng/mL for baicalin and 2-2000 ng/mL for geniposide.The method was successfully applied to compare the pharmacokinetics of the analytes between juvenile and adult rats after oral administration of Qingkailing Granules.AUC was bigger in adult rats,while t1/2 was longer in juvenile rats.Conclusion:These results suggested that the absorption and elimination of baicalin and geniposide in juvenile rats was lower than that in adult rats.Additional attention should be paid to the pharmacokinetic difference when Qingkailing Granules were used in children.