Epileptic spike is an indicator of hyper-excitability and hyper-synchrony in the neural networks. The inhibitory effects of spikes on theta rhythms (4-8 Hz) might be helpful to understand the mechanism of epileptic damage on the cognitive functions. To quantitatively evaluate the inhibitory effects of spikes on theta rhythms, intracerebral electroencephalogram (EEG) recordings with both sporadic spikes (SSs) and spike-free transient period between adjacent spikes were selected in 4 patients in the status of rapid eyes movement (REM) sleep with temporal lobe epilepsy (TLE) under the pre-surgical monitoring. The electrodes of hippocampal CA3 and entorhinal cortex (EC) were employed, since CA3 and EC built up one of key loops to investigate cognition and epilepsy. These SSs occurred only in CA3, only in EC, or in both CA3 and EC synchronously. Theta power was respectively estimated around SSs and during the spike-free transient period by Gabor wavelet transform and Hilbert transform. The intermittent extent was then estimated to represent for the loss of theta rhythms during the spike-free transient period. The following findings were obtained: (1) The prominent rhythms were in theta frequency band; (2) The spikes could transiently reduce theta power, and the inhibitory effect was severer around SSs in both CA3 and EC synchronously than that around either SSs only in EC or SSs only in CA3; (3) During the spike-free transient period, theta rhythms were interrupted with the intermittent theta rhythms left and theta power level continued dropping, implying the inhibitory effect was sustained. Additionally, the intermittent extent of theta rhythms was converged to the inhibitory extent around SSs; (4) The average theta power level during the spike-free transient period might not be in line with the inhibitory extent of theta rhythms around SSs. It was concluded that the SSs had negative effects on theta rhythms transiently and directly, the inhibitory effects aroused by SSs sustained during the spike-free transient period and were directly related to the intermittent extent. It was indicated that the loss of theta rhythms might qualify exactly the sustained inhibitory effects on theta rhythms aroused by spikes in EEG. The work provided an argumentation about the relationship between the transient negative impact of interictal spike and the loss of theta rhythms during spike-free activity for the first time, offered an intuitive methodology to estimate the inhibitory effect of spikes by EEG, and might be helpful to the analysis of EEG rhythms based on local field potentials (LFPs) in deep brain.
CA3 Region, Hippocampal ; physiopathology ; Electroencephalography ; Entorhinal Cortex ; physiopathology ; Epilepsy, Temporal Lobe ; physiopathology ; Humans ; Male ; Theta Rhythm

OBJECTIVETo explore the effect of recombinant human erythropoietin (rhEPO) on expression of brain-derived neurotrophic factor (BDNF) in different brain regions of aging rats.

METHODSForty male SD rats were randomized equally into negative control group, D-galactose group, EPO treatment group, and positive control group. Rat models of subacute aging were established by continuous subcutaneous injection of 5% D-galactose. Immunohistochemical staining was used to analyze the variation of BDNF expressions in different brain regions of the aging rats with different treatments.

RESULTSSignificant brain region-specific differences in BDNF expression were found among the rats in different groups. Compared with those in the negative control group, the numbers of BDNF-positive cells in the hippocampal CA1 region, CA3 region, dentate gyrus (DG) and frontal cortex were all decreased obviously in D-galactose group (P<0.05) but increased in both EPO group and the positive control group (P<0.05) without significant differences between the latter two groups. In the rats in the same group, the number of BDNF-positive cells varied markedly in different brain regions (P<0.05), and the expression level of BDNF was the highest in the frontal cortex followed by the hippocampal CA3 region and the dentate gyrus, and was the lowest in the hippocampal CA1 region.

CONCLUSIONTreatment with rhEPO enhances the expression of BDNF in rat neural cells, suggesting that rhEPO may protect the nervous system from aging by regulating the BDNF pathway.

Aging ; Animals ; Brain-Derived Neurotrophic Factor ; metabolism ; CA1 Region, Hippocampal ; metabolism ; CA3 Region, Hippocampal ; metabolism ; Dentate Gyrus ; metabolism ; Erythropoietin ; pharmacology ; Frontal Lobe ; metabolism ; Galactose ; Humans ; Male ; Neurons ; drug effects ; metabolism ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Recombinant Proteins ; pharmacology

Pioglitazone (PGZ), a synthetic peroxisome proliferator-activated receptor gamma agonist, is known to regulate inflammatory process and to have neuroprotective effects against neurological disorders. In the present study, we examined the effects of 30 mg/kg PGZ on excitotoxic neuronal damage and glial activation in the mouse hippocampus following intracerebroventricular injection of kainic acid (KA). PGZ treatment significantly reduced seizure-like behavior. PGZ had the neuroprotective effect against KA-induced neuronal damage and attenuated the activations of astrocytes and microglia in the hippocampal CA3 region. In addition, MPO and NFkappaB immunoreactivities in the glial cells were also decreased in the PGZ-treated group. These results indicate that PGZ had anticonvulsant and neuroprotective effects against KA-induced excitotocix injury, and that neuroprotective effect of PGZ might be due to the attenuation of KA-induced activation in astrocytes and microglia as well as KA-induced increases in MPO and NFkappaB.
Animals ; Astrocytes ; CA3 Region, Hippocampal ; Hippocampus* ; Kainic Acid ; Mice* ; Microglia ; Nervous System Diseases ; Neuroglia ; Neurons* ; Neuroprotective Agents ; PPAR gamma

We have previously reported that the intracerebroventricular (i.c.v.) administration of kainic acid (KA) results in significant neuronal damage on the hippocampal CA3 region. In this study, we examined possible changes in the blood glucose level after i.c.v. pretreatment with KA. The blood glucose level was elevated at 30 min, began to decrease at 60 min and returned to normal at 120 min after D-glucose-feeding. We found that the blood glucose level in the KA-pretreated group was higher than in the saline-pretreated group. The up-regulation of the blood glucose level in the KA-pretreated group was still present even after 1~4 weeks. The plasma corticosterone and insulin levels were slightly higher in the KA-treated group. Corticosterone levels decreased whereas insulin levels were elevated when mice were fed with D-glucose. The i.c.v. pretreatment with KA for 24 hr caused a significant reversal of D-glucose-induced down-regulation of corticosterone level. However, the insulin level was enhanced in the KA-pretreated group compared to the vehicle-treated group when mice were fed with D-glucose. These results suggest that KA-induced alterations of the blood glucose level are related to cell death in the CA3 region whereas the up-regulation of blood glucose level in the KA-pretreated group appears to be due to a reversal of D-glucose feeding-induced down-regulation of corticosterone level.
Animals ; Blood Glucose* ; CA3 Region, Hippocampal ; Cell Death ; Corticosterone ; Down-Regulation ; Glucose ; Insulin ; Kainic Acid ; Mice* ; Neurons ; Plasma ; Up-Regulation

The purpose of the present study is to explore the relationship of spatial learning ability and specific electrical activities of neural oscillations in the rat. The fast and general avoidance response groups were selected on the basis of the animals' responses to the electric shock in Y type maze, and their local field potentials (LFPs) of hippocampal CA3 area were recorded by wireless telemetry before and after shock avoidance training, respectively. The components of neural oscillations related to spatial identifying and learning ability were analyzed. The results showed that, compared with the general avoidance response group, the fast avoidance response group did not show any differences of LFPs in hippocampal CA3 area before electric shock avoidance trial, but showed significantly increased percentages of 0-10 Hz and 30-40 Hz rhythm in right hippocampal CA3 area after the shock avoidance training (P < 0.01 or P < 0.05). Fast Fourier transform showed that percentage increase of 0-10 Hz band occurred mainly in θ (3-7 Hz) frequency, and 30-40 Hz frequency change was equivalent to the γ1 band. Furthermore, compared with those before training, only the percentages of β, β2 (20-30 Hz) and γ1 rhythm increased (P < 0.01 or P < 0.05) in fast avoidance response rats after training, while the θ rhythm percentage remained unchanged. In contrast, θ rhythm percentage and the large amplitude (intensity: +2.5 - -2.5 db) θ waves in right CA3 area of general avoidance response rats were significantly reduced after training (P < 0.01). These results suggest that the increased percentages of β2 and γ1 rhythm and high-level (unchanged) percentage of θ rhythm in the right hippocampus CA3 area might be related to strong spatial cognition ability of fast avoidance response rats.
Animals ; Avoidance Learning ; Beta Rhythm ; CA3 Region, Hippocampal ; physiology ; Electroshock ; Gamma Rhythm ; Rats ; Spatial Learning ; Theta Rhythm

OBJECTIVETo observe the expression of p38 MAPK and HSP 70 in CA3 and dentate gyrus (DG) regions of the hippocampus of rats induced by limb ischemic preconditioning (LIP).

METHODSNinety-six rats were randomly divided into sham and LIP groups. And the animals in the LIP group were further divided into LIP 6 h, LIP 12 h, LIP 1 d, LIP 2 d, LIP 3 d, LIP 4 d and LIP 5 d subgroups according to the time of reperfusion after LIP. Immunohistochemical staining and Western blot were used to observe the expression of p38 MAPK and HSP 70 in CA3 and DG regions of the hippocampus.

RESULTSThe results of the immunohistochemical staining and Western blot were consistent, which indicated that there were fluctuation in the p-p38 MAPK and HSP 70 expression in CA3 and DG regions after LIP compared with those of the sham group. The expression of p-p38 MAPK began to be up-regulated 1d after LIP and reached its peak at 3 d and lasted for 4 d after LIP. However, the expression of HSP 70 was significantly up-regulated 2 d after LIP compared to the sham group, reached its peak at 3 d and lasted until the 4 d after LIP.

CONCLUSIONLIP up-regulates the expression of p38 MAPK and HSP 70 in the CA3 and DG regions of the hippocampus of rats.

Animals ; CA3 Region, Hippocampal ; metabolism ; Dentate Gyrus ; metabolism ; Extremities ; blood supply ; HSP70 Heat-Shock Proteins ; metabolism ; Ischemic Preconditioning ; Male ; Rats ; Rats, Wistar ; p38 Mitogen-Activated Protein Kinases ; metabolism

OBJECTIVE: To observe the effect of Naoling decoction on the learning and memory behaviors and the expression of microglia and IL-6 in hippocampal CA3 region of rats with Alzheimer's disease (AD), and to elucidate the potential mechanism. METHODS: Thirty SD rats were randomly divided into 5 groups: a normal group, a sham-operation group, an AD group, a Naoling decoction group and a Naofukang group. The spatial learning and memory behaviors of the rats were investigated by water maze and Y-maze. The Alzheimer's disease model was established by injecting Aβ1-42 into the hippocamal of the rats. Expression of OX-42 (one of the microglia specific markers) and IL-6 in the CA3 region of hippocamal was measured by immunohistochemical stain. RESULTS: Morris water maze experiment showed that the escape latency of hidden platform in the AD group was significantly delayed (P<0.05) and the average times of passing was decreased (P<0.05). Y-maze test showed that the times needed to the learn how to evade the electrical stimulation in the AD group was most than in other groups (P<0.05). Compared with the AD group, the Morris water maze test and Y-maze test of the Naoling decoction group were significantly different (P<0.05). The expression of OX-42 and IL-6 in the CA3 region of hippocamal in the Naoling decoction group was decreased (P<0.05). CONCLUSION Naoling decoction can improve learning and memory, and weaken the expression of OX-42 and IL-6 in hippocampal CA3 of AD rats, which may partly be the therapeutic mechanism of Naoling decoction for AD.
Alzheimer Disease ; drug therapy ; metabolism ; Animals ; CA3 Region, Hippocampal ; metabolism ; pathology ; Disease Models, Animal ; Drugs, Chinese Herbal ; therapeutic use ; Female ; Interleukin-6 ; genetics ; metabolism ; Learning ; drug effects ; Male ; Memory ; drug effects ; Microglia ; pathology ; Rats ; Rats, Sprague-Dawley

OBJECTIVEDivision of the CA1, CA3 and dentate gyrus (DG) regions of the hippocampus of Wistar rat under the stereomicroscope.

METHODSTwenty-four Wistar rats were randomly assigned to three groups. (1) The brain was sectioned coronally (n = 6). The sections were stained with thionin and the morphology of cells in each region of the hippocampus was observed under microscopy. (2) The hippocampus was dissected out and observed on the whole. Then, the CA1, CA3 and DG regions of the hippocampus were divided. Every region divided was sectioned, and the morphology of cells was observed. (3) Rats with brain ischemia or not were also decapitated and the HSP 70 expressions were observed in CA1, CA3 + DG regions by Western blot and immunohistochemical staining (n = 12).

RESULTS(1) The CA1, CA3 and DG regions of the hippocampus could be clearly observed in coronal section of the brain stained by thionin. (2) Under the stereomicroscope, the CA1 and DG regions of the hippocampus could be separated along the hippocampal fissure between them in ventral surface of the hippocampus. The CA3 and DG regions of the hippocampus could be separated along a fissure between them. The appearance of cells in the sections of the divided CA1, CA3 and DG specimens is consistent with that in the brain coronal sections, respectively. (3) The results of Western blot indicated that the HSP 70 expression of the brain ischemia group was up-regulated significantly in CA3 + DG regions compared with the sham group. However, HSP 70 expression has no significant changes in CA1 region. The above results were consistent with those of the immunohistochemical staining.

CONCLUSIONThe CA1, CA3 and DG regions of the hippocampus of Wistar rat could be divided under stereomicroscope, and the divided each region was sensible for detection of protein using Western blot.

Animals ; CA1 Region, Hippocampal ; anatomy & histology ; metabolism ; CA3 Region, Hippocampal ; anatomy & histology ; metabolism ; Dentate Gyrus ; anatomy & histology ; metabolism ; Male ; Rats ; Rats, Wistar

OBJECTIVE: To evaluate the effect of "Shuganjieyu" (SGJY) capsules on neuronal apoptosis in hippocampal CA3 area and the expression of caspase-3 in the brain of rat depression model, and to investigate its pharmacological mechanisms in depression treatment. METHODS: Adult male SD rats were randomly divided into 4 groups: a control, a model, a SGJY and a fluoxetine group. The rat depression model was established under chronic unpredictable mild stress (CUMS) and separate feeding. The behaviors were measured by open-field test, sucrose consumption and forced swimming test. We observed the neuronal morphology structure and neuronal apoptosis in the hippocampal CA3 area. We detected the rat caspase-3 expression level of medial prefrontal cortex ( mPFC) and hippocampal CA3 area by Western blot. RESULTS: After 21-day stress, compared with the model group, spontaneous activity and sucrose consumption and preference percentage of the rats in the SGJY group significantly increased, while the immobility time in forced swimming test, the number of apoptotic cells and the protein levels of caspase-3 significantly reduced (P<0.01 or 0.05). There was no significant difference between the SGJY group and the fluoxetine group (P>0.05). CONCLUSION SGJY capsules can reduce the depression symptoms of CUMS and help to increase hippocampal neuron generation, survival and neogenesis, reduce the protein levels of caspase-3, and reverse neurocyte apoptosis in the rat depression model with the same efficacy as fluoxetine.
Animals ; Apoptosis ; drug effects ; CA3 Region, Hippocampal ; enzymology ; pathology ; Capsules ; Caspase 3 ; metabolism ; Depression ; drug therapy ; enzymology ; pathology ; Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; Male ; Neurons ; pathology ; Rats ; Rats, Sprague-Dawley

AIMTo study the effects of yi-zhi II (a compond of Chinese Traditional Medicine) on the alteration of synaptic structure in hippocampal CA3 and maintenance of memoy.

METHODSBy using the method of oral administration of yi-zhi II, the step-through test and electron microscopy, the latency of step-through and synaptic structure in hippocamal CA3 were tested.

RESULTS(1) The mice which had been given yi-zhi II prolong significantly the latency of step through (P < 0.05 or P < 0.01) on the 1st, 6th and 12th day after learning. (2) On the 6th and 12th day after learning, the length of synaptic active zone were markly improved in yi-zhi II and control, but that of yi-zhi II was better than that of control. (On the 6th day after learning, the number of perforated synapses and axo-dendrite synapses were significantly improved by the yi-zhi II (P < 0.05).

CONCLUSIONThe yi-zhi II could improve the learning and memory in mice. It migth improve the memory by increasing the length of synaptic active zone and the number of perforated synapses and axo-dendrite synapses in hippocampal CA3.

Animals ; Avoidance Learning ; drug effects ; CA3 Region, Hippocampal ; drug effects ; physiology ; Chromosome Pairing ; drug effects ; Drugs, Chinese Herbal ; pharmacology ; Male ; Memory ; drug effects ; Mice ; Neuroprotective Agents ; pharmacology