To explore the mechanism of interleukin-1beta (IL-1beta) in the onset of seizure and the effect of IL-1beta on the expression of adenylyl cyclase (AC) in rats with seizure induced by L-glutamate. Experimental rats were first injected with IL-1beta and then L-glutamate (a dose under the threshold) was injected into the right lateral ventricle. The rats were sacrificed 4 h after the onset of epileptic activity and examined for changes in behavior, immunohistochemistry and compared with those with seizure induced by L-glutamate alone. It was found that the expression of AC in hippocampal and neocortex of rats with seizure induced by IL-1beta and L-glutamate were stronger than that of control group (P<0.05), without significant difference found between the L-glutamate group and IL-1beta plus L-glutamate group in the expression of AC, the latent period and the severity of seizure. When IL-ra were given (i.c.v.) first, there was no epileptic activity and the expression of AC did not increase. There were no differences in the expression of AC of rats with IL-1ra and that of control rats. But when 2-methyl-2-(carboxycyclopropyl) glycine (MCCG) was given (i.c.v.) first, the strongest expression of AC, the shortest latent period and the the most serious seizure activities were observed. The results indicated that IL-1beta could facilitate the onset of epilepsy induced by L-glutamate through IL-1R, metabotropic glutamate receptors might work with IL-1R and the increased expression of AC might be involved in the process.
Adenylyl Cyclases ; biosynthesis ; genetics ; Animals ; Glutamic Acid ; Hippocampus ; metabolism ; Interleukin-1 ; pharmacology ; Male ; Neocortex ; metabolism ; Rats ; Seizures ; chemically induced ; enzymology

BACKGROUND: Retrograde cerebral perfusion(RCP) is currently used for brain protection during aorta surgery, however, for the safety of it, various data published so far are insufficient. We performed RCP using pig and investiaged various parameters of cerebral metabolism and brain injury after RCP under deep hypothermia. MATERIAL AND METHOD: We used two experimental groups: in group I(7 pigs, 20 kg), we performed RCP for 120 minutes and in group II (5 pigs, 20 kg), we did it for 90 minutes. Nasopharyngeal temperature, jugular venous oxygen saturation, electroencephalogram were continuously monitored, and we checked the parameters of cerebral metabolism, histological changes and serum levels of neuron-specific enolose(NSE) and l actic dehydrogenase(LDH). Central venous pressure during RCP was mainained in the range of 25 to 30 mmHg. RESULT: Perfusion flow rates(ml/min) during RCP were 130+/-57.7(30 minutes), 108.6+/-55.2(60 minutes), 107.1+/-58.8(90 minutes), 98.6+/-58.7(120 minutes) in group I and 72+/-11.0(30 minutes), 72+/-11.0(60 minutes), 74+/-11.4(90 minutes) in group II. The ratios of drain flow to perfusion flow were 0.18(30 minutes), 0.19(60 minutes), 0.17(90 minutes), 0.16(120 minutes) in group I and 0.21, 0.20, 0.17 in group II. Oxygen consumptions(ml/min) during RCP were 1.80+/-1.37(30 minutes), 1.72+/-1.23(60 minutes), 1.38+/-0.82(90 minutes), 1.18+/-0.67(120 minutes) in group I and 1.56+/-0.28(30 minutes), 1.25+/-0.28(60 minutes), 1.13+/-0.26(90 minutes). We could observe an decreasing tendency of oxygen consumption after 90 minutes of RCP in group I. Cerebrovascular resistance(dynes sec cm-5) during RCP in group I incrased from 71370.9+/-369145.5 to 83920.9+/-49949.0 after the time frame of 90 minutes(p<0.05). Lactate(mg/min) appeared after 30 minutes of RCP and the levels were 0.15+/-0.07(30 minutes), 0.18+/-0.10(60 minutes), 0.19+/-0.19(90 minutes), 0.18+/-0.10(120 minutes) in group I and 0.13+/-0.09(30 minutes), 0.19+/-0.03(60 minutes), 0.29+/-0.11(90 minutes) in group II. Glucose utilization, exudation of carbon dioxide, differences of cerebral tissue acidosis between perfusion blood and drain blood were maintained constantly during RCP. Oxygen saturation levels(%) in drain blood during RCP were 22.9+/-4.4(30 minutes), 19.2+/-4.5(60 minutes), 17.7+/-2.8(90 minutes), 14.9+/-2.8(120 minutes) in group I and 21.3+/-8.6(30 minutes), 20.8+/-17.6(60 minutes), 21.1+/-12.1(90 minutes) in group II. There were no significant changes in cerebral metabolic parameters between two groups. Differences in serum levels of NSE and LDH between perfusion blood and drain blood during RCP showed no statistical significance. Serum levels of NSE and LDH after resuming of cardipulmonary bypass decreased to the level before RCP. Brain water contents were 0.73+/-0.03 in group I and 0.69+/-0.06 in group II and were higher than those of the controls(p<0.05). The light microscopic findings of cerebral neocortex, basal ganglia, hippocampus(CA1 region) and cerebellum showed no evidence of cerebral injury in two groups and there were no different electron microscopy in both groups(neocortex, basal ganglia and hippocampus), but they were thought to be reversible findings. CONCLUSIONS: Although we did not proceed this study after survival of pigs, we could perform the RCP successfully for 120 minutes with minimal cerebral metabolism and no evidence of irreversible brain damage. The results of NSE and LDH during and after RCP should be reevaluated with survival data.
Acidosis ; Aorta ; Basal Ganglia ; Brain Injuries ; Brain* ; Carbon Dioxide ; Central Venous Pressure ; Cerebellum ; Electroencephalography ; Glucose ; Hemodynamics* ; Hypothermia ; Metabolism ; Microscopy, Electron ; Neocortex ; Oxygen ; Oxygen Consumption ; Perfusion* ; Phosphopyruvate Hydratase* ; Swine*

BACKGROUND: Recent increases in use of sevoflurane have made active researches on its effects in the cerebral metabolism. However, no specific data on brain glucose metabolism has been reported from human study. We compared the brain glucose metabolism during sevoflurane anesthesia with that of propofol anesthesia using positron emission tomography (PET) in the same human volunteers. METHODS: PET scan was performed two times at intervals of one week in each eight volunteers. One scan was performed in sevoflurane anesthesia, and the other was performed in propofol anesthesia. Each was titrated to the point of unconsciousness. The scan was obtained by the 18fluorodeoxyglucose technique. Relative cerebral glucose metabolic rate (rCMRg) was assessed with statistical parametric mapping. RESULTS: The regions of decreased rCMRg during sevoflurane aneshesia were the visual cortex, posterior parietal association area, primary somatosensory area, and premotor area. During propofol anesthesia the decreased regions were the visual inferotemporal area and prefrontal association area in addition to those area of sevoflurane anesthesia. The increased regions were the partial prefrontal association area, basal ganglia, cingulate, olfactory-limbic cortex, midbrain, and pons during sevoflurane anesthesia, and the primary motor area, insula, thalamus, medulla along with those area of sevoflurane during propofol anesthesia. CONCLUSION: Propofol suppressed the rCMRg of neocortex area more than sevoflurane, and sevoflurane suppressed the rCMRg of paleocortex, telencephalon more than propofol when the unconsciousness level was achieved by anesthesia. Sevoflurane produces different effects on relative brain glucose metabolism with propofol.
Anesthesia* ; Basal Ganglia ; Brain ; Electrons* ; Glucose* ; Healthy Volunteers ; Humans* ; Mesencephalon ; Metabolism* ; Neocortex ; Pons ; Positron-Emission Tomography* ; Propofol* ; Rabeprazole ; Telencephalon ; Thalamus ; Unconsciousness ; Visual Cortex ; Volunteers

BACKGROUNDThere are no reports on exnografting cultured human fetal neocortical cells in this infracted cavities of adult rat brains. This study was undertaken to observe whether cultured human cortical neurons and astrocytes can survive and grow in the infarcted cavities of adult rat brains and whether they interconnect with host brains.

METHODSThe right middle cerebral artery was ligated distal to the striatal branches in 16 adult stroke-prone renovascular hypertensive rats. One week later, cultured cells from human embryonic cerebral cortexes were stereotaxically transferred to the infarcted cavity of 11 rats. The other 5 rats receiving sham transplants served as controls. For immunosuppression, all transplanted rats received intraperitoneal injection of cyclosporine A daily starting on the day of grafting. Immunohistochemistry for glial fibrillary acidic protein (GFAP), synaptophysin, neurofilament, and microtubule associated protein-2 (MAP-2) was performed on brain sections perfused in situ 8 weeks after transplantation.

RESULTSGrafts in the infarcted cavities of 6 of 10 surviving rats consisted of bands of neurons with an immature appearance, bundles of fibers, and GFAP-immunopositive astrocytes, which were unevenly distributed. The grafts were rich in synaptophysin, neurofilament, and MAP2-positive neurons with long processes. The graft/host border was diffuse with dendrites apparently bridging over to the host brain, into which neurofilament immunopositive fibers protruded.

CONCLUSIONCultured human fetal brain cells can survive and grow in the infarcted cavities of immunodepressed rats and integrate with the host brain.

Animals ; Astrocytes ; transplantation ; Brain ; pathology ; Cell Proliferation ; Cell Survival ; Cells, Cultured ; Cerebral Infarction ; metabolism ; pathology ; therapy ; Fetal Tissue Transplantation ; Glial Fibrillary Acidic Protein ; analysis ; Humans ; Microtubule-Associated Proteins ; analysis ; Neocortex ; cytology ; Neurons ; transplantation ; Rats ; Synaptophysin ; analysis

The development of a cerebral organoid culture in vitro offers an opportunity to generate human brain-like organs to investigate mechanisms of human disease that are specific to the neurogenesis of radial glial (RG) and outer radial glial (oRG) cells in the ventricular zone (VZ) and subventricular zone (SVZ) of the developing neocortex. Modeling neuronal progenitors and the organization that produces mature subcortical neuron subtypes during early stages of development is essential for studying human brain developmental diseases. Several previous efforts have shown to grow neural organoid in culture dishes successfully, however we demonstrate a new paradigm that recapitulates neocortical development process with VZ, OSVZ formation and the lamination organization of cortical layer structure. In addition, using patient-specific induced pluripotent stem cells (iPSCs) with dysfunction of the Aspm gene from a primary microcephaly patient, we demonstrate neurogenesis defects result in defective neuronal activity in patient organoids, suggesting a new strategy to study human developmental diseases in central nerve system.
Action Potentials ; physiology ; Biomarkers ; metabolism ; Cell Culture Techniques ; Embryoid Bodies ; cytology ; metabolism ; Gene Expression ; Humans ; Induced Pluripotent Stem Cells ; cytology ; metabolism ; Lateral Ventricles ; cytology ; growth & development ; metabolism ; Microcephaly ; genetics ; metabolism ; pathology ; Models, Biological ; Mutation ; Neocortex ; cytology ; growth & development ; metabolism ; Nerve Tissue Proteins ; deficiency ; genetics ; Neurogenesis ; genetics ; Neurons ; cytology ; metabolism ; Organoids ; cytology ; metabolism ; PAX6 Transcription Factor ; genetics ; metabolism ; Patch-Clamp Techniques ; SOXB1 Transcription Factors ; genetics ; metabolism ; Zonula Occludens-1 Protein ; genetics ; metabolism

The basic changes are to transform the levels of many genes' transcriptions and translations when methamphetamine is injected into the organism. Those genes enclose four classes: genes intermediating the damages or death of neurons,genes involving circadian rhythms of activity, genes concerning the abnormality of behaviors and some genes difficult to be classified. The transformations of the transcriptions or translations of these genes cooperate to produce many clinic syndromes of methamphetamine-addictors. Moreover, the study of these genes can provide testimonies to forensic identification.
Animals ; Circadian Rhythm/genetics* ; Forensic Medicine ; Gene Expression Regulation/drug effects* ; Humans ; Methamphetamine/pharmacology* ; Neocortex/metabolism* ; Neurons/pathology* ; Proto-Oncogene Proteins c-bcl-2/metabolism* ; Proto-Oncogene Proteins c-fos/metabolism* ; Substance-Related Disorders ; Transcription, Genetic/drug effects* ; Translocation, Genetic/drug effects*

AIMTo investigat the effects of donepezil on delayed rectifier-like potassium currents (IK) in rat hippocampus and neocortex.

METHODSWhole cell configuration of the patch-clamp techniques were used to characterize IK in acutely isolated rat hippocampal and neocortical pyramidal neurons.

RESULTSThe slowly inactivating outward currents (IK) were recorded in all cells under investigation. Donepezil in micromolar concentrations were shown to supress the IK of all cells in a dose-dependent and voltage-dependent manner. The steady-state activation curves of IK were characterized by half-activation potentials of -15.5 mV in hippocampal and -4.1 mV in neocortical pyramidal neurons and were changed to -26.2 mV and -18.6 mV, respectively, after perfusion with donepezil (10 mumol.L-1).

CONCLUSIONAt concentrations as low as 1 mumol.L-1, donepezil was found to block the IK in a voltage-dependent manner in hippocampus and neocortex. This effect may be synergistic with the anticholinesterase activity of donepezil to increase its therapeutic effectiveness.

Animals ; Cholinesterase Inhibitors ; pharmacology ; Delayed Rectifier Potassium Channels ; Hippocampus ; cytology ; In Vitro Techniques ; Indans ; pharmacology ; Male ; Neocortex ; cytology ; Neurons ; drug effects ; metabolism ; Patch-Clamp Techniques ; Piperidines ; pharmacology ; Potassium Channels ; drug effects ; physiology ; Potassium Channels, Voltage-Gated ; Pyramidal Cells ; drug effects ; metabolism ; Rats ; Rats, Wistar