Animals ; Brain Chemistry ; Brain Ischemia ; metabolism ; physiopathology ; Cerebral Cortex ; metabolism ; Dementia ; metabolism ; physiopathology ; Humans ; Microdialysis ; Reperfusion Injury ; metabolism ; physiopathology

OBJECTIVETo investigate antigen-induced changes of leukotriene B(4)(LTB(4))content and LTA(4)-hydrolase mRNA expression in lung tissue and cerebral cortex in sensitized rats.

METHODSThe contents of LTB(4) in lung tissue and cerebral cortex homogenates and LTA(4)-hydrolase mRNA expression after antigen challenge by aerosol were respectively detected by reverse-phase high performance liquid chromatography(RP-HPLC) and semi-quantitative RT-PCR.

RESULTThe LTB(4) levels in lung tissue and cerebral cortex homogenates in asthmatic rats were significantly higher than those in control (P%0.05), and LTA4-hydrolase mRNA expression was also increased in asthmatic group. Dexamethason(DXM, 0.5 mg/kg, i.p.) decreased the LTB(4) content and inhibited the LTA(4)-hydrolase mRNA expression significantly in asthmatic rats(P%0.05).

CONCLUSIONLTB(4) content and LTA(4)-hydrolase mRNA expression in cerebral cortex and lung tissue are increased in asthmatic rats, and there may exist neuroimmunological cross-talking between central nervous system and lung tissue in asthma.

Animals ; Asthma ; metabolism ; Cerebral Cortex ; chemistry ; metabolism ; Epoxide Hydrolases ; genetics ; Female ; Leukotriene B4 ; analysis ; Lung ; chemistry ; metabolism ; Male ; RNA, Messenger ; analysis ; Rats ; Rats, Sprague-Dawley

OBJECTIVETo observe the change of nitric oxide (NO) and expression of nuclear factor-kappa B (NF-kappaB) in the cortex of cerebral infarction rat induced by photochemical reaction, and study the effect of extract from Cornus officinalis (whose main ingredient is iridoid glycoside) in the course of disease.

METHODAfter rats were fed with experimental drugs for 7 days, the model of cerebral infarction was induced. Spectrophotography and immunohistochemistry were used to detect the change of the content of NO, NOS and the expression of NF-kappaB in the cortex.

RESULTCompared with control group, distinct infarction was visible in the model group, and the content of NO, the activity of NOS and the positive cell number of NF-kappaB were increased obviously. Compared with model group, the extract of C. officeinalis decreased the area of infarction, the content of NO, the activity of NOS and the positive cell number of NF-kappaB.

CONCLUSIONThe iridoid glycoside of C. officinalis may have therapeutical effect on cerebral infarction through regulating the content of NO and NF-kappaB.

Animals ; Cerebral Cortex ; metabolism ; pathology ; Cerebral Infarction ; metabolism ; pathology ; Cornus ; chemistry ; Drugs, Chinese Herbal ; isolation & purification ; pharmacology ; Male ; NF-kappa B ; metabolism ; Nitric Oxide ; metabolism ; Nitric Oxide Synthase ; metabolism ; Plants, Medicinal ; chemistry ; Random Allocation ; Rats ; Rats, Sprague-Dawley

OBJECTIVETo investigate the effect of lead exposure on copper and copper metalloenzyme and the intervention effect of quercetin.

METHODSTwenty-four specific pathogen-free male Sprague-Dawley rats of good health were randomly divided into control group (n = 8), lead acetate group (n = 8), and lead acetate + quercetin group (n = 8). The rats in lead acetate group were poisoned by drinking water with 1 g/L lead acetate for 8 weeks, while the rats in control group were fed by drinking water with sodium acetate of the same volume for 8 weeks; the rats in lead acetate+quercetin group were intraperitoneally injected with quercetin (30 mg × kg-1 × d-1) for 8 weeks while drinking water with lead acetate. The Morris water maze was used to test the learning and memory abilities of rats. The lead and copper levels in the serum, hippocampus, cortex, and bone were measured by graphite furnace atomic absorption spectrometry. The level of advanced glycation end products, activity of Cu/Zn superoxide dismutase (SOD), and content and activity of ceruloplasmin (CP) in the hippocampus and serum were measured using a test kit. HE staining was performed to observe the pathological changes in the hippocampus.

RESULTSThe Morris water maze test showed that the latency in lead acetate group (52.50±12.04 s) was significantly longer than that in control group (28.08±7.31 s) (P<0.05), and the number of platform crossings was significantly lower in the lead acetate group than in the control group. Compared with those in the control group, the lead levels in the cortex and hippocampus in lead acetate group increased 2.72-fold and 3.79-fold, and the copper in the cortex and hippocampus, and serum free copper levels in lead acetate group increased 1.15-fold, 1.48-fold, and 6.44-fold. Compared with the control group, the lead acetate group had a lower content of CP in the hippocampus (1.23±0.40 U/mg provs0.78±0.08 U/mg pro) and 31.81%and 19.49%decreases in CP content and Cu/Zn SOD activity. Free copper level in serum was positively correlated with the latency and lead levels in the serum, cortex, and hippocampus. The escape latency of rats in lead acetate + quercetin group was decreased by 42.15% (P<0.05). The lead levels in the cortex and hippocampus in lead acetate + quercetin group (0.246 ± 0.58 µg/g and 0.202±0.049 µg/g) were significantly lower than those in lead acetate group (0.391±0.49 µg/g and 0.546±0.120 µg/g), but the free copper and copper levels in the hippocampus and cortex were not significantly reduced. The lead acetate + quercetin group had higher Cu/Zn SOD activity and CP content in the hippocampus than the lead acetate group (P < 0.05). The light microscope observation showed that the number of cells in the hippocampus was reduced with disordered arrangement in the lead acetate group; with quercetin intervention, the hippocampus damage was reduced.

CONCLUSIONLead exposure results in disorder of copper homeostasis, while quercetin may alleviate the damage induced by lead to some extent.

Animals ; Cerebral Cortex ; chemistry ; Copper ; blood ; Hippocampus ; chemistry ; Homeostasis ; Learning ; drug effects ; Male ; Memory ; drug effects ; Organometallic Compounds ; toxicity ; Quercetin ; pharmacology ; Rats, Sprague-Dawley ; Superoxide Dismutase ; metabolism

AIMTo design and synthesize novel AchE inhibitors.

METHODSThe condensation of 2-bromo-5, 6-dimethoxy-indan-1-one with various aminoalkyl phenols in the presence of K2CO3 and acetonitrile gave the corresponding title compounds, and the in vitro AchE and BchE inhibitory activities were evaluated by the modified Ellman method.

RESULTSSixteen novel target compounds 8a - p were synthesized, their structures were confirmed by 1H NMR, MS, IR and elemental analysis. Preliminary pharmacological test demonstrated that most of these compounds displayed high AchE inhibitory activities, the IC50 of the most potent inhibitor 8h was 50.0 nmol x L(-1), similar to that of Huperzine A (IC50 = 53.0 nmol x L(-1)), while all the compounds were almost inactive against BchE.

CONCLUSION2-Phenoxy-indan-1-one derivatives exhibit high activities of AchE inhibition and are worthy of further investigation.

Acetylcholinesterase ; metabolism ; Animals ; Cerebral Cortex ; enzymology ; Cholinesterase Inhibitors ; chemical synthesis ; chemistry ; pharmacology ; Drug Design ; Indans ; chemical synthesis ; chemistry ; pharmacology ; Inhibitory Concentration 50 ; Molecular Structure ; Rats ; Structure-Activity Relationship

OBJECTIVETo investigate the toxicity of fipronil in mice and the therapeutic effects of diazepam and phenobarbital sodium.

METHODSMice were administered by gastric tube with fipronil at six doses and their behavioral changes, pathological changes in their major viscera under light and electron microscopy and deaths were observed after acute poisoning. Distribution and quantity of nerve cells positive in glutamic acid (Glu) or gamma-aminobutyric acid (gamma-GABA) in the brain of mice were detected by immunohistochemical methods and micro-image analysis. The time of death time and survival rate were observed and compared between the varied groups of mice injected intraperitoneally with diazepam and phenobarbital sodium, respectively, 0.5 h after poisoning by fipronil at dose of 90 mg/kg.

RESULTSAll the mice acutely poisoned by fipronil at varied doses showed some exciting symptoms in the central nervous system (CNS), including convulsion. Nuclear membrane space slightly expanded, neuroglia cells vacuolized and nerve fiber demyelinated under electron microscopy. The number and area of cells positive in Glu in the cerebral cortex of mice acutely poisoned by fipronil increased significantly, as compared to those in control mice. There was no significant difference in the number and area of cells positive in gamma-GABA in the hippocampal CA(1) region between poisoned and normal control groups. Survival rate of mice treated with diazepam or phenobarbital sodium was 58 percent.

CONCLUSIONMice with acute poisoning by fipronil appeared exciting symptoms in CNS, leading to damage in its nerve cells. Immunohistochemical techniques showed the damage could be related with the over-expression of glutamate transmitter in CNS. Early use of diazepam or phenobarbital sodium in treatment for acutely poisoned mice by fipronil could get better therapeutic efficacy.

Acute Disease ; Animals ; Cerebral Cortex ; chemistry ; Female ; Glutamic Acid ; metabolism ; Male ; Mice ; Mice, Inbred ICR ; Poisoning ; drug therapy ; Pyrazoles ; poisoning ; gamma-Aminobutyric Acid ; metabolism

In order to provide a complete picture of pathogenesis in cerebral ischemia, cerebral cortex in MCAO rats were analysed for alteration in their proteomes. Comparative proteome analysis was used to compare signal corresponding to individual cerebral cortex proteins on a two-dimensional gel between MCAO rats and the normal control (NC) group. After sample preparation, two-dimensional electroghoresis separated proteins were stained with Commassie Brilliant Blue. The image data were analyzed on a Dell computer using Image Master v 3.01 software. In cerebral cortex, 30 proteins were differentially expressed in MCAO rats compared with NC. There were 11 spots significantly increased, 15 spots significantly decreased and Adenylate kinase isoenzyme 1 was detected only in NC group, biliverdin reductase B, small inducible cytokine A4 [Precursor] only in MCAO group. Peroxiredoxin 2 divided into two points in MCAO6h group. In the end, this approach may lay a foundation for the further investigation of pathogenic mechanisms in cerebral ischmic injury.
Animals ; Brain Ischemia ; genetics ; metabolism ; Cerebral Cortex ; metabolism ; Electrophoresis, Gel, Two-Dimensional ; Gene Expression Profiling ; Infarction, Middle Cerebral Artery ; genetics ; metabolism ; Nerve Tissue Proteins ; chemistry ; genetics ; metabolism ; Proteome ; Proteomics ; methods ; Random Allocation ; Rats ; Rats, Wistar

OBJECTIVETo study the effect of oxysophoridine (OSR) on glutamate (Glu) and gamma aminobutyric acid (GABA) immuno-reaction positive neurons in the cortex and hippocampus of rats.

METHODImmunohistochemistry method (SABC) and the micrographic analysis technique were employed to monitor the effect of OSR in the variations of Glu and GABA immunoreaction positive neurons in the cortex and hippocampus of rats.

RESULTOSR administrated icv (10 mg) significantly increased the number of GABA immuno-reaction positive neurons while decreasing the number of glu immunoreaction positive neurons in cortex and hippocampus in rats (P < 0.05).

CONCLUSIONResults showed that the change of Glu and GABA caused by OSR may responsible for its inhibitory effects on the central nervous system.

Alkaloids ; isolation & purification ; pharmacology ; Animals ; Cerebral Cortex ; metabolism ; ultrastructure ; Glutamic Acid ; metabolism ; Hippocampus ; metabolism ; ultrastructure ; Immunohistochemistry ; methods ; Male ; Neurons ; metabolism ; ultrastructure ; Plants, Medicinal ; chemistry ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Sophora ; chemistry ; gamma-Aminobutyric Acid ; metabolism

AIMTo investigate glutamate-induced [Ca2+]i changes in cultured rat neonatal cortical astrocytes after hypoxia/reoxygenation, H2O2 or high concentration of L-glutamate injury. In the meantime, the effects of Gingko biloba extract (GbE) were examined.

METHODS[Ca2+]i changes in astrocytes were monitored by laser scanning confocal microscopy with the Ca2+ sensitive fluorescent probe fluo-3.

RESULTSAfter astrocytes were impaired by hypoxia/reoxygenation, H2O2 (50 micromol x L(-1)) or L-glutamate (0.25 mmol x L(-)), the exogenous glutamate (27 micromol x L(-1)) could not induce increase of [Ca2+]i, but decrease by (3.3 +/- 1.6)%, (81 +/- 11)% and (81 +/- 7)%, respectively. Pretreatment with GbE (10 mg x L(-1)) could not improve injured astrocytic glutamate response. But after pretreatment with GbE (100 mg x L(-1)), glutamate-induced [Ca2+]i elevation of astrocytes after hypoxia/reoxygenation, H2O2 or high concentration of L-glutamate injury were (135 +/- 98)%, (117 +/- 93)% and (89 +/- 36)%, respectively. Nimodipine (1.6 mg x L(-1)) could also reverse the abnormal response of astrocytes after different injury.

CONCLUSIONHypoxia/reoxygenation, H2O2 and high concentration of L-glutamate impaired astrocytes' response to exogenous L-glutamate, and then bidirectional communication between astrocytes and neurons could not take place. GbE could improve the abnormal responses and maintain the normal function of astroglical network. These effects support that GbE has potential beneficial actions against brain injury.

Animals ; Astrocytes ; cytology ; metabolism ; Calcium ; metabolism ; Cell Hypoxia ; Cells, Cultured ; Cerebral Cortex ; cytology ; metabolism ; Drugs, Chinese Herbal ; isolation & purification ; pharmacology ; Ginkgo biloba ; chemistry ; Glutamic Acid ; toxicity ; Hydrogen Peroxide ; toxicity ; Plant Leaves ; chemistry ; Plants, Medicinal ; chemistry ; Rats ; Reperfusion Injury

OBJECTIVETo evaluate protective effects of Rheum tanguticum polysaccharides (RTP) on traumatic brain injury (TBI) in rats.

METHODThe polysaccharides (RTP) were extracted from Tanguficum Maxim. 120 rats were divided into 15 groups, with 8 rats in each group. RTP at 100, 200 and 400 mg x kg(-1) were administrated orally once a day for five days, and model of brain injury was made by dropping weight method.

RESULTRTP reduced water content and malondialdehyde (MDA) levels, and increased total SOD activity and Na+-K+ ATPase activity after injuried.

CONCLUSIONThe polysaccharides may be one of the effective comptents in Rheum tanguticum, showing significant neuroprotective effects.

Animals ; Brain Injuries ; enzymology ; metabolism ; pathology ; Cerebral Cortex ; enzymology ; ultrastructure ; Male ; Malondialdehyde ; metabolism ; Neuroprotective Agents ; pharmacology ; Plants, Medicinal ; chemistry ; Polysaccharides ; isolation & purification ; pharmacology ; Rats ; Rats, Sprague-Dawley ; Rheum ; chemistry ; Sodium-Potassium-Exchanging ATPase ; metabolism ; Superoxide Dismutase ; metabolism