coriaria-lactone and Epilepsy

Epilepsy is a chronic disease, while epileptogenesis is a latent period where brain will be transformed into an epileptic one. Mechanisms of epileptogenesis remain unclear.. We aim to provide information of hippocampal lipidomic changes related with epileptogenesis in two kindling models. Combining hippocampal structural imaging indices, our study also attempts to assess biochemical alterations as a function of epileptogenesis in a non-invasive way.. We constructed two kinds of chemical kindling models, which have long been used as models of epileptogenesis. Two kindling and one control groups were all subjected to structural imaging acquisition after successfully kindled. Voxel-based morphometry, a postprocessing method for brain imaging data, was used to segment and extract hippocampal gray matter volume for subsequent integrative analysis. LC-MS based lipidomic analysis was applied to identify distinct hippocampal lipidomic profiles between kindling and control groups. Further, we regress hippocampal structural indices on lipids to identify those associated with both epileptogenesis and brain structural changes.. We report distinct lipidomic profiles between kindling groups and control. A total of 638 lipids were detected in all three groups. Among them were 98 individual lipids, showing significant alterations, in particular lipid class of phosphatidylethanolamine (PE), glucosylceramide and phosphatidylcholine. Hippocampal gray matter volumes were found significant different between groups (P = 0.0223). After combining brain imaging data, we demonstrate several individual PE, namely PE(O-18:1_22:3), PE(O-18:1_22:6) and PE(18:1_18:1), are associated with both epileptogenesis and hippocampal gray matter volume.. This study suggests metabolic pathway of PE might involve in epileptogenesis. Also, for the first time, we link level of PE with structural brain imaging indices, in an attempt to potentiate the futuristic application of noninvasive brain imaging techniques to identify epileptogenesis in its latent period.

Topics: Animals; Brain; Disease Models, Animal; Epilepsy; Hippocampus; Kindling, Neurologic; Lactones; Lipidomics; Male; Neuroimaging; Pentylenetetrazole; Phosphatidylethanolamines; Rats

Epilepsy is a chronic and recurrent disease of the central nervous system, with a complex pathology. Recent studies have demonstrated that the activation of glial cells serve an important role in the development of epilepsy. The objective of the present study was to investigate the role of high‑mobility group box‑1 (HMGB1) in mediating the activation of glial cells through the toll‑like receptor 4 (TLR4)/nuclear factor (NF)‑κB signaling pathway in seizure, and the underlying mechanism. The brain tissue of post‑surgery patients with intractable epilepsy after resection and the normal control brain tissue of patients with craniocerebral trauma induced intracranial hypertension were collected. The expression level and distribution pattern of HMGB1, OX42 and NF‑κB p65 were detected by immunohistochemistry. HMGB1, TLR4, receptor for advanced glycation end products (RAGE), NF‑κB p65 and inducible nitric oxide synthase (iNOS) expression levels were detected by western blotting, and serum cytokine levels of interleukin (IL)‑1, IL‑6, tumor necrosis factor (TNF)‑α, transforming growth factor (TGF)‑β and IL‑10 in patients with epilepsy and craniocerebral trauma were detected by ELISA. And cell model of epilepsy was established by coriaria lactone (CL)‑stimulated HM cell, and the same factors were measured. The potential toxic effect of HMGB1 on HM cells was evaluated by MTT and 5‑ethynyl‑2‑deoxyuridine assays. The results demonstrated that compared with the control group, levels of HMGB1, TLR4, RAGE, NF‑κB p65 and iNOS in the brain of the epilepsy group were significantly increased, and increased cytokine levels of IL‑1, IL‑6, TNF‑α, TGF‑β and IL‑10 in patients with epilepsy were also observed. At the same time, the above results were also observed in HM cells stimulated with CL. Overexpression of HMGB1 enhanced the results, while HMGB1 small interfering RNA blocked the function of CL. There was no significant toxic effect of HMGB1 on HM cells. In conclusion, overexpression of HMGB1 potentially promoted epileptogenesis. CL‑induced activation of glial cells may act via up‑regulation of HMGB1 and TLR4/RAGE receptors, and the downstream transcription factor NF‑κB.

Topics: Animals; Biomarkers; Brain; Cell Survival; Disease Models, Animal; Epilepsy; Gene Expression; HMGB1 Protein; Humans; Immunohistochemistry; Lactones; Microglia; NF-kappa B; Signal Transduction; Toll-Like Receptor 4

The earliest records of traditional Chinese medicine (TCM) prevention and treatment of epilepsy dated back to famous "Huang Di Nei Jing." TCM "spasmolytic powder" (equal-ratio compatibility of scorpion and centipede) is a famous prescription which was recognized as a useful add-on drug for refractory epilepsy in clinical observations. Multidrug resistance gene (mdr1) product Pgp overexpression in blood-brain barrier and blood-cerebrospinal fluid barrier is well recognized as the drug resistance mechanism of refractory epilepsy. Here, we established the drug-resistant epilepsy Sprague-Dawley rat model induced by Coriaria Lactone and treated these rats with topiramate and verapamil and low dose, middle dose, and high dose of spasmolytic powder by intragastric administration for 1 week. Electroencephalogram, real-time PCR, and immunohistochemistry were respectively used to detect epileptic discharge frequencies and amplitudes and expression of mdrl mRNA and Pgp on hippocampus and temporal lobe of rats. The results showed that the seizure decreases significantly in the high- and middle-dose groups of spasmolytic powder and topiramate group; in addition, mdr1 mRNA and Pgp expressions on hippocampus and temporal lobe of these drug intervention groups were significantly less than the model group (P < 0.05). These findings indicate that inhibition of intracephalic Pgp expression is possibly one of mechanisms of spasmolytic powder treating refractory epilepsy.

Topics: Animals; Anticonvulsants; Arthropods; ATP Binding Cassette Transporter, Subfamily B, Member 1; Disease Models, Animal; Dose-Response Relationship, Drug; Drugs, Chinese Herbal; Electroencephalography; Epilepsy; Fructose; Hippocampus; Kindling, Neurologic; Lactones; Male; Medicine, Chinese Traditional; Rats; Rats, Sprague-Dawley; Temporal Lobe; Tissue Extracts; Topiramate; Verapamil

To investigate the different expression of GluR5 and GluR6 in rat astrocyte induced with Coriaria Lactone (CL) and ATPA and to discuss the possible mechanism of the inducing epileptic model.. Astrocyte of neonate rats was treated with CL and ATPA respectively and the astrocyte treated with normal saline as control. The mRNA and protein levels of GluR5 and GluR6 were detected by RT-PCR and western blotting.. Compared with the control, the expression of GluR5 was increased significantly in the astrocyte induced by ATPA (P < 0.05), however, there was no alteration of GluR6 expression. The expression of GluR5 and GluR6 were decreased significantly in CL-treated group (P < 0.05).. The present study showed ATPA up-regulated mRNA and protein levels of GluR5, but coriaria lactone down-regulated the GluR5 and GluR6 of astrocyte. The results indicate that there are different pathologic mechanisms of GluR5 and GluR6 in different neurotoxicants inducing model of epilepsy. The molecular mechanism need to be studied further in the future.

Topics: Animals; Animals, Newborn; Astrocytes; Epilepsy; GluK2 Kainate Receptor; Isoxazoles; Lactones; Propionates; Rats; Rats, Sprague-Dawley; Receptors, Kainic Acid; RNA, Messenger

We instituted an investigation to elucidate the role of Ca2+ and calcium channels in epileptogenesis and to analyze the mechanism by which coriaria lactone (CL) regulates intracellular Ca2+ concentration. The hippocampal neurons of Sprague-Dawley rats (post natal days 7 to 14) were acutely isolated and loaded with calcium-sensitive fluorescent indicator Fluo-3/AM. Intracellular calcium concentration ([Ca2+]i) changes were measured using laser scanning confocal microscopy. The study included five groups, namely the CL group, the NiCl2 plus CL group, the Nifedipine plus CL group, the NiCl2+ Nifedipine plus CL group, and the control group. The results indicated that 20 microl/ml CL induced a significant increase of [Ca2+]i in hippocampal neurons when compared to the control (P < 0.01), the mean fluorescent intensity of intracellular calcium displaying an increase from 5.46 +/- 2.37 to 34.03 +/- 3.45. Although the increase of relative intracellular fluorescent intensity was delayed by 3 or 4 minutes in the NiCl2 plus CL group, the Nifedipine plus CL group, and the NiCl2+ Nifedipine plus CL group, yet the use to 20 microl/ml CL in these 3 groups caused a significant ascending level of the fluorescent intensities (from 3.94 +/- 1.75 to 30.18 +/- 4.22; from 3.38 +/- 1.11 to 36.39 +/- 3.97; from 3.05 +/- 1.02 to 28.05 +/- 2.71), and the effect was comparable to that observed in the CL group (P > 0.05). So CL can increase [Ca2+]i in acutely isolated rat hippocampal neurons. This effect can be delayed but can not be completely blocked by NiCl2 and Nifedipine. These findings indicate that CL can increase [Ca2+]i by other means besides T- and L-type voltage-gated calcium channels, and that CL can increase the excitability of neurons and play a role in the epileptogenesis process.

Topics: Animals; Animals, Newborn; Calcium; Calcium Channels; Epilepsy; Female; Hippocampus; Lactones; Male; Neurons; Rats; Rats, Sprague-Dawley

The hippocampal neurons of Sprague-Dawley rat (post natal days 7 to 14) were acutely isolated using trypsin and mechanical dissociation. AgNO3 staining was performed to identify them. Voltage-dependent inward calcium currents were recorded by employing the patch-clamp technique in the whole-cell voltage-clamp mode. With different stimulation processes, we studied the changes of low voltage activated (LVA) calcium currents, the transient and sustained components of high voltage-activated calcium currents (HVA) in the hippocampal neuron membrane. The effects of CL on the peak currents in the neuron membrane were assessed and analyzed. The main sustained components ofHVA were L-type calcium currents. The HVA calcium currents were slowly inactivated in 300 ms. The changes of the current amplitude of the sustained components of HVA were insignificant with the holding potential of -100 mV and -50 mV which indicated that the inactivation could be removed with the potential of -50 mV. The HVA calcium currents were evoked by depolarizing voltage steps over the range of -70 mV to +50 mV for 300ms with the holding potential of -50 mV and the threshold potential of -40 mV or so. The HVA and LVA calcium currents were evoked by the same stimulation with the holding potential of -100 mV and the total calcium currents appeared at the potential of -60 mV. The amplitude of peak currents significantly increased (P<0.05). The transient LVA calcium currents as the peak calcium currents were evoked by depolarizing voltage steps over the range of -70 mV to -30 mV with the holding potential of -100 mV. Both HVA and LVA calcium currents appeared over the range of -30 mV to +10 mV. The HVA calcium currents mainly appeared above the membrane potential of +10 mV. There was no obvious borderline between these components. About 3 minutes after the application of CL, the peak density of LVA calcium currents in 20 microl/ml and 40 microl/ml CL group increased respectively (75.56% +/- 23.09% vs. 66.12% +/- 19.09%) (P<0.05). CL increased the peak density of HVA calcium currents in a concentration-dependent way, with enhancement by 18.15% +/- 4.98% (P<0.05) and 32.80% +/- 3.58% (P<0.01) after the application of 20 microl/ml and 40 microl/ml CL. The effects of CL on the calcium currents will contribute to the enhanced excitability of hippocampal neurons, modulate some calcium-dependent processes and boost epileptic discharges. All of them play an important role in the CL-induced epileptogen

Topics: Animals; Animals, Newborn; Calcium; Calcium Channels; Cell Separation; Epilepsy; Female; Hippocampus; Lactones; Male; Neurons; Patch-Clamp Techniques; Rats; Rats, Sprague-Dawley

To explore the effect of coriaria lactone (CL)-activated astrocyte-conditioned medium on the cerebral TNF-alpha of normal rats, the CL-activated astrocyte-conditioned medium (ACM) was injected into the lateral ventricle of SD rats. The rats were observed for behavioral changes, and the changes of the expression of TNF-alpha in the cerebral cortex and hippocampus were immunohistochemically examined by employing SP method. TNF-alpha level was assessed by means of radioimmunoassay in homogenate of cerebral cortex and hippocampus as well as cerebrospinal fluid. Seizure episodes were observed in ACM group 30 min after the ACM injection, but they were not observed in the control group. Immunohistochemical detection showed that the immunoreaction of TNF-alpha in hippocampus and cerebral cortex of rats were stronger than that of the control group 4 h after the ACM injection (P<0. 05). In this group, the concentrations of TNF-alpha in homogenate of cerebral cortex and hippocampus and cerebrospinal fluid were higher than those of the control group (P<0.05). It is suggested that the ACM activated by CL can enhance the expression of TNF-alpha in normal rats, and is related to epileptogenesis.

Topics: Animals; Astrocytes; Cerebral Cortex; Culture Media, Conditioned; Epilepsy; Hippocampus; Immunohistochemistry; Lactones; Male; Radioimmunoassay; Rats; Rats, Sprague-Dawley; Tumor Necrosis Factor-alpha

To detect the expression of Metabotropic Glutamate Receptor 1alpha (MGLUR1alpha) in the different brain areas of the kindled epilepsia models of rats by Coriaria Lactone (CL).. Thirty male SD rats were divided into 3 groups and were given intramuscular injections of 0.75, 1.0 and 1.25 ml/kg Coriaria Lactone respectively. 5 rats in the control group were given intramuscular injection of 1.0 ml/kg saline. After the kindling models were completed, the EcoG of all groups were recorded with the multi-electrophysiology recorder to view whether the EcoG of kindled rats accord with their seizures and to know whether there are differencees in EcoG among the kindled, non-kindled and control groups. The coronary sections of brain tissue were HE stained and MGLUR1alpha immunohistochemistry stained, and were observed under light microscope.. The kindled rats had all grade (Simialowski scale) seizures after CL injection and their seizures accorded with their EcoG features. The MGLUR1alpha expression of kindled rats in hippocampus and temporal cortex outside hippocampus was stronger than that of non-kindled and control rats (P < 0.05); the strong expression was noted to be of no obvious difference between neuron and glia.. The MGLUR1alpha expression of kindled rats in hippocampus and temporal cortex outside hippocampus is stronger than that of non-kindled and control. It is possible that MGLUR1alpha participates in epileptic seizures.

Topics: Animals; Brain; Electroencephalography; Epilepsy; Hippocampus; Kindling, Neurologic; Lactones; Male; Rats; Rats, Sprague-Dawley; Receptors, Metabotropic Glutamate; Temporal Lobe

This research sought to disclose the regulatory effect of Coriaria lactone (CL) on the Ca(2+)-activated K+ channel in hippocampal pyrimidal neurons of Wistar rats in epileptogenesis.. Cell-attached and inside-out methods of patch clamp technique were used to record the activity of single channel. The sample data were stored in a computer and analyzed by the application of Pclamp softwares.. 1. By means of inside-out method, the KCa channels (120.34 +/- 25.12) pS on the membrane of hippocampal pyrimidal neurons showed a distinct dependence on calcium concentration (n = 6) and on voltage (n = 17), and the channels could be blocked by TEA. 2. With the use of cell-attached method, the KCa channels could be activated by CL apparently (n = 25, P < 0.01). 3. In the conditions where the neuronal membranous voltage was kept at 20 mV and the [Ca2+]i at 10(-8) mol/L in bath solution, the CL at concentrations from 0 microliter/ml to 1.0 microliter/ml could make the open state probability of KCa to increase from 0.025 to 0.553 (P < 0.01), the mean opening time (ms) to prolong from 1.875 +/- 0.412 to 6.829 +/- 0.136, and the mean closing time (ms) to decrease from 179.342 +/- 13.831 to 6.412 +/- 1.383 (n = 25, P < 0.01).. The membranous KCa activation induced by CL may play an important negative feedback regulating role in the mechanism of epileptogenesis.

Topics: Animals; Animals, Newborn; Cells, Cultured; Epilepsy; Female; Hippocampus; Lactones; Male; Membrane Potentials; Patch-Clamp Techniques; Potassium Channels, Calcium-Activated; Pyramidal Cells; Rats; Rats, Wistar

To acquire knowledge about the effect of Coriaria lactone (CL) on ATP-sensitive potassium channels (KATP) in cultured pyrimidal neurons of rats and the role of KATP in epileptogenesis.. Experiments were conducted by the use of cell culture technique and single channel patch clamp technique.. The reversion potential of neuron KATP was nearly 0 mV under the condition of the same high K+ level in both bath solution and pole solution. The channel could be blocked by TEA, and the channel current could be induced by 30 mumol/L DNP but inhibited by 0.5 mol/L ATP. The conductance of KATP channel current was 78.23 +/- 12.04 pS, and this KATP channel could be remarkably activated by CL and specifically blocked by Glibenclamide.. The activation of neuron KATP may play a role of decreasing the action potential and thus protecting the neurons from the seizure induced by CL.

Topics: Adenosine Triphosphate; Animals; Animals, Newborn; Brain; Cells, Cultured; Epilepsy; Female; Lactones; Male; Neurons; Patch-Clamp Techniques; Potassium Channels; Pyramidal Tracts; Rats; Rats, Wistar

Intracellular recording method of electrophysiology was used to study the effect of microinjection of coriaria lactone (CL) into hippocampus on membrane potential of hippocampal neurons in rats. The membrane potential in 34 neurons of 12 rats were recorded. The results showed that CL induced depolarization of all of 34 neurons examined. Among the 34 neurons, 15 had paroxysmal depolarization accompanied by spike discharge in cluster and spike discharge in cluster ceased when membrane was hyperpolarized, 7 showed continuous depolarization accompanied by continuous spike discharge and 12 had only depolarizing response. The results suggest that injection of CL into hippocampus may lead to an increase of excitability of local neurons accompanied by different patterns of epileptioform discharge.

Topics: Animals; Electroencephalography; Epilepsy; Female; Hippocampus; Lactones; Male; Membrane Potentials; Microelectrodes; Microinjections; Neurons; Rats; Rats, Wistar

To investigate the exact mechanism of epileptogenesis induced by coriaria lactone (CL), the effect of CL on NMDA receptor mediated current (IAsp) in rat hippocampal CA1 neurons was investigated by using nystatin perforated whole-cell patch clamp. 10(-6)-10(-4) mol/L Asp acted on NMDA receptors and elicited an inward current (IAsp) at a holding potential (VH) of -40 mV in presence of 10(-6) mol/L glycine and absence of Mg2+ extracellularly. CL enhanced NMDA receptor mediated current induced by Asp, but had no effect on threshold concentration, EC50, Hill coefficient as well as maximal-effect concentration and reversal potential of IAsp. The effect had no relationship with holding potential. These results showed that CL could enhance NMDA receptor mediated current to increase [Ca2+]i of neurons by acting on Gly site, thereby inducing epilepsy.

Topics: Animals; Animals, Newborn; Biological Transport, Active; Calcium; Drugs, Chinese Herbal; Electrophysiology; Epilepsy; Hippocampus; Lactones; Neurons; Patch-Clamp Techniques; Rats; Rats, Sprague-Dawley; Receptors, N-Methyl-D-Aspartate

The effects of coriaria lactone (CL) on gamma-aminobutyric acid (GABA) secretion, glutamic acid decarboxylase (GAD) activity and glutamate (Glu) receptor binding were studied by using cultured neurons, P2 component and synaptic membranes from rat cerebral cortex. It was found that GABA secretion was depressed by CL, the depression rate was 8.3%, 10.6%, 14.5% at 12h 24h 48h respectively. GAD activity was depressed by CL in concentration of 0.15-150 mumol/L. The depression rate was 1.32%, 5.96%, 13.24%, 18.76% respectively. The Glu receptor binding capability was decreased by CL with obvious dose-effect relation in the extent of 2.8-350 mumol/L; the decrease rate was 4.4%, 12.7%, 15.2%, 19.5% respectively. The difference was significant as compared to control (P < 0.01).

Topics: Animals; Cerebral Cortex; Depression, Chemical; Drugs, Chinese Herbal; Epilepsy; gamma-Aminobutyric Acid; Glutamate Decarboxylase; Lactones; Rats; Receptors, Glutamate; Synaptic Membranes

The immune adherence function of red blood cells in 17 rats was studied. It was found that the rosette rate of red blood cell C3b receptor (RBC-C3bRR) was 7.45 +/- 1.36% in the epilepsy group (8 rats), and 10.84 +/- 1.77% in the control group (9 rats); and that the rosette rate of red blood cell immune complex (RBC-ICR) was 7.42 +/- 2.62% in the epilepsy, and 10.80 +/- 1.72% in the control. As compared with the control group, the rosette rate of red blood cell C3b receptor was remarkably decreased in the epilepsy group (P < 0.05). There was no significant difference between the two groups in RBC-ICR. The results from this study demonstrated that the CL-induced seizures might result in decrease in red blood cell immune adherence function of the epilepsy rats.

Topics: Animals; Antigen-Antibody Complex; Drugs, Chinese Herbal; Epilepsy; Erythrocytes; Immune Adherence Reaction; Lactones; Male; Rats; Rats, Sprague-Dawley; Receptors, Complement 3b; Rosette Formation

Ten male Wistar rats were divided into two groups. The experimental rats were injected with subconvulsive dosage of coriaria lactone (1 mg/kg) intramuscularly every 3.5 days to induce kindling seizures. The controls were injected with normal saline. Cerebral motor cortex of kindling rats was taken at the time between seizures and layer V was compared morphologically with that of the control. The number of neurons and neuroglias was counted from light micrographs. The numerical density and length fraction of boutons on the surface of pyramidal somata were measured from electron micrographs with MIAS 300 type image analyser. The number of synapses in neuropil was counted directly and the areal fraction of various constitute in neuropil was measured stereologically from EM photos. In the experimental rats, the number of neurons remained unchanged and the numerical density and length fraction of boutons on the surface of pyramidal somata showed no change, either. The number of synapses (or presynaptic terminals) decreased significantly in neuropil, but the areal fraction of synaptic terminals had no change and the areal fraction of dendrites and unmyelinated fibers decreased. The areal fraction of myelinated fibers increased significantly. The number of neuroglias and the areal fraction of neuroglial processes increased significantly in the experimental rats. The data suggest that the major morphological changes are manifested as a decline in the pyramidal dendritic components, especially dendritic spines, and the axons with its terminals from superficial neurons in motor cortex layer V of the kindling rats induced by coriaria lactone, besides the neurogliosis which is similar to that occurring in other long-term seizures.

Topics: Animals; Epilepsy; Kindling, Neurologic; Lactones; Male; Motor Cortex; Random Allocation; Rats; Rats, Wistar

Twenty nine adult SD rats in the experiment were randomly separated into two groups. Nineteen rats of them were intramuscularly injected (i.m.) with Coriaria lactone (CL, 2.5 mg/kg for female rat; 30 mg/kg for male rat) two days a time, continued 28 times, to induce repeated seizures, as the experimental group. The control group (n = 10) was injected with normal saline (N.S.) in the same volume as that of CL. The rats of experimental group were subdivided into a treatment group (n = 9) with SC1001Na (200 mg/kg) and a placebo group (n = 10) receiving N.S. in the same volume as that of SC1001 Na. All rats of repeated seizure were administered once every day for a week. The results indicated that SC1001Na (200 mg/kg) could inhibit in some degree the growth of immune organs (spleen and thymus) and significantly decrease the ADA activity of thymus, cerebrum and cerebellum, suggesting that the antiepileptic mechanism of SC1001Na is probably related with the decreased activity of ADA and the increased adenosine level in brain.

Topics: Adenosine Deaminase; Animals; Anticonvulsants; Brain; Epilepsy; Female; Lactones; Male; Rats; Rats, Sprague-Dawley; Sodium; Spleen; Thymus Gland

Eighteen fully kindled rabbits, whose epilepsy had been produced by intrahippocampal (i.h.) injections of 2 microliters of diluted solution containing 0.32 or 0.55 micrograms of coriaria lactone (CL), were separated into three groups. One of them was used as the control group. For seizure, all animals were given CL (0.6-1 micrograms/2 microliter i.h.). Ten minutes later, the verapamil (VR) group of six rabbits was treated with VR (1.5 or 2 mg/kg i.m. 2.5 or 5 micrograms/2 microliters i.h.); the normal saline (NS) group (six rabbits) received 0.8 ml/kg (i.m., in the same volume as that of the VR 2 mg/kg injection) or 2 microliters (i.h.) of NS; the control group of six received neither VR nor NS. The experiments were made once every eight days. Hippocampal EEGs of all animals were recorded by telemetric method and their behavior after injection was observed continuously in 4-7 hours. The results of the experiment indicated that the i.h. administration of 2.5 or 5 micrograms/2 microliters of VR is effective on hippocampal kindled seizures induced by CL in rabbits, but the curative effects of the i.m. administration of 1.5 or 2 mg/kg of VR were less notable than those of the i.h. administration.

Topics: Animals; Electroencephalography; Epilepsy; Female; Hippocampus; Injections, Intraventricular; Kindling, Neurologic; Lactones; Male; Rabbits; Verapamil

Fourteen male Wistar rats were divided into two groups. The experimental rats were injected with subconvulsive dosage of coriaria lactone (1 mg/kg) intramuscularly per 3.5 days. The controls were injected with normal saline. After 26 injections, the loci coeruleus of kindling rats were studied with the noradrenaline (NA) fluorescence histochemical technique at the time between seizures. The NA fluorescence could be clearly visualized under fluorescent microscope. The intensity of fluorescence was reflected by autoexposure-meter of the fluorescent microscope. The brighter the fluorescence, the shorter the autoexposure time. The intensity of NA fluorescence in the locus coeruleus of experimental animals was weaker than that of the controls. Since NA plays an inhibitory role in cerebral cortex, the decrease of NA, either induced by repeated injections of coriaria lactone or due to the time of sample taken after seizure, needs further study.

Topics: Animals; Epilepsy; Histocytochemistry; Kindling, Neurologic; Lactones; Locus Coeruleus; Male; Microscopy, Fluorescence; Norepinephrine; Rats; Rats, Wistar

The ultrastructural changes of hippocampus and cerebral cortex neurons were derived from the rabbits kindled by coriaria lactone and from the kindled rabbits after treatment with SC1001 Na. The results of experiment showed that the hippocampus and cerebral cortex neurons in the kindled group had some degenerative changes, such as the swelling mitochondria, dilated rough endoplasmic reticulum and Golgi complexes when the injuries of neurons were not serious, but the seriously injured neurons were subjected to rupture of the cell membrane and solution of most organella, with only a small amount of degenerative organella. In the group treated with SC1001 Na, the ultrastructure of brain neurons demonstrated a tendency of recreation to normal which showed that SC1001 Na had cured many of the degenerative brain cells. This suggested that active treatment is very important for the epileptic patients.

Topics: Animals; Anticonvulsants; Brain; Cerebral Cortex; Epilepsy; Female; Hippocampus; Kindling, Neurologic; Lactones; Male; Neurons; Rabbits; Sodium

Kindling model of epilepsy induced by intraperitoneal injection of Coriaria lactone (CL) was used in the experiment. The dose of CL was 1.25 mg/kg. Thirty rats in various periods of kindling were killed and the materials of cerebral cortex, hippocampus and cerebellum were drawn. The enzyme activities of AchE, NADHD, CCO, LDH, SDH, AcP, ANAE and AkP of these areas were observed with enzyme histochemical techniques. In another three kindled rats, two blank control rats and two NS control rats, the ultrastructure of neurons in hippocampus were observed. The results of experiments showed an increased activity of enzymes related to saccharometabolism and energy metabolism, indicating that the metabolism of brain in rats was increased by repeated kindling seizures. The mechanism of kindling seizure induced by CL may be related to inhibitory effect of CL on AchE activity of brain. The degeneration damage of brain neurons in kindled rats may result from using CL for a long time.

Topics: Acetylcholinesterase; Animals; Brain; Epilepsy; Hippocampus; Histocytochemistry; Injections, Intraperitoneal; Kindling, Neurologic; Lactones; Male; Rats; Rats, Inbred Strains

Healthy rabbits weighing 1.7-2.4 kg were used. According to Sawyer's atlas the stainless steel cannula and recording electrode were implanted into the left hippocampus of each animal. The kindling experiments were started one week after the surgical operation. For kindling, all animals received injection of 2 microliters of diluted solution containing 0.55 or 0.32 microgram of coriaria lactone (CL) every second day, through the single stainless steel cannula previously implanted in the hippocampus. Hippocampal EEG of all the animals was recorded by telemetric method and the behavior of them was observed at the same time. Eighteen fully kindled rabbits were separated into three groups. The SC1001 Na group of six rabbits was treated with SC1001 Na (100 mg/kg, i.m.), the PB Na group (six rabbits) received phenobarbital Na (30 mg/kg, i.m.), and the control group of six was treated with placebo (normal saline, i.m., in the same volume as that of the SC1001 Na injection); injections were administered once a day for two courses of treatment (one course of treatment was 1 week). The results of the experiment indicated that SC1001 Na (100 mg/kg) had certain effects on hippocampal kindled seizures induced by CL, but its curative effects were not more notable than those of PB Na (30 mg/kg).

Topics: Animals; Anticonvulsants; Epilepsy; Female; Hippocampus; Kindling, Neurologic; Lactones; Male; Phenobarbital; Rabbits; Sodium

In order to create chemical kindling effect model of epilepsy, fifty-six adult male SD rats were used in this experiment, and randomly divided into five groups. An intramuscular injection of various subthreshold dose of CL (0.50, 0.75, 1.00, 1.25 mg/kg) was given repeatedly per 3.5 days in the I-IV groups, V group received injections of normal saline of the same volume as control. ECoG and EHG were recorded by telemetric method through electrodes chronically implanted in the cortex and hippocampus. The behavior of them was observed at the same time. The results of experiments showed that: 1. CL can lead to the typical behavior, ECoG and EHG of epilepsy. So it is an effective chemical kindling agent of causing epilepsy, and hippocampus was more than cortex to CL. 2. The relationship between the seizure stages induced by CL various dose groups and the mean injection times had a linear correlation through linear regressive processing (r value: 0.9276-0.99732). The difference comparison of linear regressive intercept of various groups was significant (P less than 0.05), respectively. It is indicated that the more the dose of CL increase, the less the injection times of reaching seizure stages. 3. 24 rats of the experimental groups 46 rats had reached kindling criterion through 40 times injection of CL. The difference comparison between I, II and III, IV groups of kindling rats was quite significant (P less than 0.01), respectively. 4. The mean persistence time of all kindled rats was 113.42 days. The longest persistence time of them was 224 days.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Animals; Brain; Disease Models, Animal; Dose-Response Relationship, Drug; Drugs, Chinese Herbal; Electrophysiology; Epilepsy; Kindling, Neurologic; Lactones; Rats; Rats, Inbred Strains

In our present study we build up a new experimental model in the rat for epilepsy by intracerebroventricular injection of Coriaria Lactone (CL) and examine the effects of electroacupuncture on epileptiform hippocampal unit activity. Three types of hippocampal units responding to CL were observed: a) positive units b) negative units and c) indifferent units. The activity of positive units may be the typical epileptiform hippocampal activity. The positive units can be inhibited by electroacupuncture (EA), while the negative units can be exhilarated by EA. No changes were observed in indifferent units. Inhibitory effects of positive units are different because of using different "acupoints". EA of Du-Mo and Taichong Kunlun in the other side of drug injection were significatively better than Taichong, Kunlun in the same side of drug injection. Effects of Du-Mo was significantly better than the effects of the points on the limb. Parameters of EA are significantly different in other side of limb points for inhibition of positive units: 5 V 1 Hz, 5 V 5 Hz greater than 1 V 5 Hz greater than 1 V 1 Hz. These data indicate that effects of EA are depend on amplitude of EA, and seem not to be concern with frequencies of EA. The amplitude and frequency of hippocampal EEG spikes can be inhibited by EA. The inhibitory role of EA on epileptiform discharges is also discussed in this paper.

Topics: Animals; Electroacupuncture; Electroencephalography; Epilepsy; Hippocampus; Injections, Intraventricular; Lactones; Male; Rats; Rats, Inbred Strains

Reserpine injection (1 mg/kg i.p.) could not only significantly reduce cAMP levels in both cerebral cortex and hippocampus in naive WC1 mice, but also potentiate the degree of seizures elicited by CL. Reserpine injection could significantly shorten CL-seizures latency and decrease its threshold, too. Reserpine pretreatment could also diminish CL seizure-induced accumulation of cAMP. These results indicated the cAMP level elevated by seizure activity was associated with monoamine neurotransmitter activity, and the seizure-induced accumulation of cAMP might take part in the process which eliminated the spread of seizure discharges and speeded up the termination of seizures.

Topics: Animals; Brain; Cyclic AMP; Epilepsy; Female; Lactones; Male; Mice; Mice, Inbred Strains; Reserpine

To study the relationship between cAMP and epilepsy, we investigated the effects of coriaria lactone (CL) on the levels of cAMP in cerebral cortex and hippocampus. Fifty normal WC1 mice were divided into 5 groups. All groups were injected with CL (2.5 mg/kg, i.m.), except the control group which was injected with NS. The concentrations of cAMP were measured after the animals had been immersed in liquid nitrogen to die at different phases of seizure development induced by CL (before seizures, in mild seizures, during severe seizures, and after severe seizures). The results indicated that the levels of cAMP in both cerebral cortex and hippocampus were significantly increased (1.73-fold and 1.33-fold) in severe seizure, and they continuously increased (1.85-fold and 1.45-fold) after severe seizures. On the other hand, no changes of cAMP were observed in mild seizures and before seizures. These data suggested that accumulation of cAMP is probably the result of seizure activity rather than the cause of seizure.

Topics: Animals; Cerebral Cortex; Cyclic AMP; Epilepsy; Female; Hippocampus; Lactones; Male; Rats; Rats, Inbred Strains

Fifty adult male Sprague-Dawley rats were divided into five groups. Intraperitoneal injections of various doses of coriaria lactone (CL, 0.75, 1.25, 1.75, and 2.0 mg/kg) and normal saline were given respectively per 2 days. The behavior of the rats was observed and the ECoG was recorded by telemetric method. The results of experiments show that a kindling model of epilepsy can be established by intraperitoneal injection of CL in rats. This chronic experimental model is of value for application because it is easily established and the rate of being kindled is relatively high, but the mortality is low, and the kindling effect can last well. The model can avert the pathological change caused by artificial injury to brain, so it is advantageous to the research on neurochemistry and ultrastructure. In our experimental condition, it is optimal to select 1.25 mg/kg or 1.75 mg/kg as the dosage of CL for establishing kindling model.

Topics: Animals; Disease Models, Animal; Epilepsy; Injections, Intraperitoneal; Kindling, Neurologic; Lactones; Male; Rats; Rats, Inbred Strains

Coriaria lactone (CL) is an active constituent of a medicinal herb used as psychosolytic in traditional Chinese medicine. Recently it has been found that CL appears to act as a convulsant agent. Subsequently both acute and chronic epilepsy models caused by CL have been established successfully. In order to observe further the epileptogenic effects of CL in vitro, the hippocampal slice technique was used in experiments with 36 slices. The results are as follows: Addition of CL to the perfusion bathing the slices of rat hippocampus increased evoked-response in body layer of CA1 in a dose-dependent manner, and induced epileptiform burst. CL augmented population spike of CA1 pyramidal neurons triggered by either orthodromic stimulus (through synapses) or antidromic stimulus (direct effect on the axon of CA1 pyramidal cells) without alteration of presynaptic fiber volley and field-EPSP, and there was no significant change in latency of burst. Finally GABA had a weak effect on CL-induced epileptiform activity. These observations suggest that CL probably has a direct effect on the soma of pyramidal neurons, CL-induced epileptiform burst may be a result of altering the innate capacity of burst and increasing the intrinsic excitability of pyramidal cell membranes.

Topics: Animals; Electrophysiology; Epilepsy; Female; Hippocampus; In Vitro Techniques; Lactones; Male; Rats; Rats, Inbred Strains

In this experiment, the calmative and anti-epileptic effects of SC1001A were observed in fifty-five tupaias (Tupaia belangeri Yunalis), both male and female, were divided into four groups. The animals of the first group were perfused with SC1001A (400mg/kg) into their stomach. The animals of the second group were injected with coriaria lactone (5mg/kg, i.m.) for inducing seizures. The remaining two groups received SC1001A 100 and 400 mg/kg respectively by the same way as that of the first group, and 1 min later, they were injected immediately with coriaria lactone (5 mg/kg, i.m.). After the drug being perfused, the behaviors of all the experimental animals were observed continuously for 2-3 h. The results of the experiment indicated that SC1001A was possessed of a calmative effect which appeared shortly after drug (mean 12.88 min) and did not sustain a long time (mean 98 min). In addition, SC1001A was obviously effective on epilepsy induced by coriaria lactone in tupaias, in reducing the seizure rate, the times of petit mal and grand mal, as well as the duration of grand mal.

Topics: Animals; Anticonvulsants; Cinnamates; Epilepsy; Female; Lactones; Male; Tupaia

Topics: Animals; Anticonvulsants; Avoidance Learning; Electroshock; Epilepsy; Lactones; Male; Memory; Mice

Topics: Animals; Avoidance Learning; Benzofurans; Epilepsy; Female; Hippocampus; Lactones; Memory; Rats; Rats, Inbred Strains

Topics: Animals; Anticonvulsants; Benzofurans; Brain; Epilepsy; Female; Lactones; Rats; Rats, Inbred Strains

Topics: Animals; Disease Models, Animal; Epilepsy; Injections, Intramuscular; Kindling, Neurologic; Lactones; Male; Medicine, Chinese Traditional; Medicine, East Asian Traditional; Plants, Medicinal; Rats; Rats, Inbred Strains

Topics: Animals; Disease Models, Animal; Epilepsy; Female; Hippocampus; Kindling, Neurologic; Lactones; Male; Medicine, Chinese Traditional; Medicine, East Asian Traditional; Microinjections; Plants, Medicinal; Rabbits