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

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

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

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

Neural stem cells (NSCs) cultured in vitro were implanted within three-dimensional (3D) and self-assembly hydrogel from IKVAV-containing peptide. The cytocompatibility of hydrogel with NSCs was explored. Neural cells harvested from the cerebral cortex of neonatal mice were dissociated mechanically and cultivated in serum-free media, and were immunohistochemically examined for Nestin, NSE (neuron specific enolase) and GFAP (Glial fibrillary acidic protein); the self-assembly hydrogel from 1 wt% amphiphilic peptide was formed with the addition of DMEM/F12 and observed under transmission electron microscope (TEM); 1 x 10(5) /ml NSCs implanted within hydrogel (3D culture system) and seeded onto the surface of coverslips covered with polylysine (two-dimensional culture system, 2D culture system) respectively were incubated without serum at 37 degrees C in 5% CO2 and 95% air. Then the cells in 3D culture system and 2D one were double-labeled with DAPI/Brdu and observed under fluorescence microscope. The Nestin-positive cells were found, and they were able to differentiate into NSE-positive neuron- like cells and GFAP-positive glial-like cells, TEM showed that the hydrogel derived from 1 wt% peptide solution was composed of nanofiber network with the fiber diameters ranging from 3 to 6 nm and the fiber length warying from 100 nm to 1.5 microm, NSCs labeled with Brdu in 2D system were thinly scattered, and those in 3D system formed many neurospheres; the positive rate in 3D was much higher than that in 2D system (P < 0.001). The self-assembly hydrogel from the amphiphilic peptide containing IKVAV sequence had good cyto-compatibility and promoted the proliferation of NSCs.
Animals ; Animals, Newborn ; Cells, Cultured ; Cerebral Cortex ; cytology ; Hydrogels ; pharmacology ; Materials Testing ; Neural Stem Cells ; cytology ; Peptides ; chemistry ; Rats ; Rats, Sprague-Dawley ; Surface-Active Agents ; chemistry

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 pathological characteristics of heroin spongiform leukoencephalopathy (HSLE).

METHODSCerebral tissue specimens were obtained from 15 patients with HSLE and the histological observations under optical and electron microscopes were carried out by HE, Bielschowsky's, and chromotrope 2R-brilliant green staining.

RESULTSHSLE was characterized primarily by spongiform vacuolar degeneration of the cerebral white matter. Neurons in the gray matter, Purkinje and granular cells in the cerebella remain intact in all the cases. Numerous vacuoles, which merged to form larger cavities, appeared in the damaged white matter, and the axons survived in the deep white matter. The myelin sheath in the cerebellar white matter sustained more severe damages than those in the cerebral white matter. No vacuoles or lymphocyte infiltration occurred in the small peripheral vessels.

CONCLUSIONHSLE is pathologically characterized by vacuolar degeneration due to primary damage of the myelin, and the spongiform vacuolar degeneration is closely associated with the severity of demyelination in the white matter.

Adult ; Autopsy ; Canavan Disease ; etiology ; pathology ; Cerebellum ; chemistry ; pathology ; ultrastructure ; Cerebral Cortex ; chemistry ; pathology ; ultrastructure ; Female ; Heroin Dependence ; complications ; Humans ; Male ; Microscopy, Electron ; Middle Aged ; Neurons ; chemistry ; pathology ; Purkinje Cells ; chemistry ; pathology ; Staining and Labeling ; methods ; Young Adult

OBJECTIVETo investigate the expression of N-methyl-D-asparate (NMDA) receptor subunit proteins after administration of different doses of pentylenetetrazol (PTZ).

METHODSAfter ip injection of a subconvulsant (35 mg/kg) and convulsant (50 mg/kg) dose of PTZ, the rats were decapitated at different time points. The levels of cortical NR1 NR2A and NR2B subunit proteins were detected by immunoblotting.

RESULT35 mg/kg PTZ and 50 mg/kg PTZ elicited different behavioral changes (P<0.001). The NR2A subunit in the cortex significantly increased 1 h after PTZ injection (P<0.05). For the 50 mg/kg group, both the NR2A and NR2B subunits proteins increased at 1 h in the cortex and then decreased; the protein levels returned to normal after 48 h. However, NR1 subunit had no changes.

CONCLUSIONThe NR2 subunit is involved in PTZ-induced seizure.

Animals ; Cerebral Cortex ; chemistry ; Dose-Response Relationship, Drug ; Male ; Pentylenetetrazole ; administration & dosage ; Rats ; Rats, Sprague-Dawley ; Receptors, N-Methyl-D-Aspartate ; analysis ; Seizures ; chemically induced ; metabolism

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

OBJECTIVETo study cortical neuron injury following recurrent epileptiform discharges induced by magnesium-free treatment in vitro.

METHODSCultured embryo cortical neurons were exposed to magnesium-free media for 3 h, then they were returned to regular media containing normal level magnesium. At different time after Mg(2+)-free treatment, trypan blue staining and determination of LDH activity were used to determine the cell viability, flow cytometry was applied to measure neuronal apoptosis, and MTT assay to study metabolic rate.

RESULTS(1) Neuronal morphology on light microscopy following Mg(2+)-free treatment showed that there were no prominent alterations. (2) At different time (6, 12, 72 h) after Mg(2+)-free treatment, neuronal viability by trypan blue staining and LDH activity showed modest changes compared with time-matched control in different culture days (6, 12, 17 d) (P > 0.05). (3) Cell apoptosis increased mildly at different time after Mg(2+)-free treatment in neurons cultured for different days, but the increase was not significant (P > 0.05). (4) Metabolic rate decreased at 6 h after Mg(2+)-free treatment (P < 0.05) in neurons cultured for 6 d, and was 86.4% of that of the control; while the rate at 24 h in neurons cultured for 12 d and 17 d also decreased (P < 0.05), being 78.7% and 70.9%, respectively, of that of the control.

CONCLUSIONSThese findings demonstrated that the injury occurred on cultured cortical neurons caused by magnesium-free-treatment-induced recurrent epileptiform discharges was mainly functional and relatively mature neurons displayed more severe and much later mitochondrial function impairment than immature neurons.

Animals ; Cerebral Cortex ; embryology ; Culture Media ; chemistry ; pharmacology ; Culture Techniques ; Magnesium ; pharmacology ; Neurons ; drug effects ; pathology ; Rats ; Rats, Wistar ; Seizures ; physiopathology