The chemical constituents and action targets of Acori Tatarinowii Rhizoma and Curcumae Radix were screened by network pharmacological method,and the mechanism of the combination of Acori Tatarinowii Rhizoma and Curcumae Radix in the treatment of epilepsy was analyzed. All chemical constituents of Acori Tatarinowii Rhizoma and Curcumae Radix were retrieved by TCMSP,and their action targets were screened. Component target PPI network was constructed. Epilepsy-related genes were retrieved from PharmGkb database,and PPI networks of disease targets were drawn by Cytoscape software. Cytoscape software was used to merge the network,screen the core network,and further analyze the gene GO function and KEGG pathway enrichment,which was verified by experimental research. One hundred and five chemical constituents of Acori Tatarinowii Rhizoma and 222 chemical constituents of Curcumae Radix were retrieved. Nineteen compounds were selected as candidate compounds according to OB and DL values. Among them,4 chemical constituents of Acori Tatarinowii Rhizoma and 15 chemical constituents of Curcumae Radix were found. A total of 88 target proteins were retrieved by retrieving TCMSP data,and PPI network was constructed. Through PharmGkb database,29 epilepsy-related genes were retrieved and disease target network was established. Cytoscape software and plug-ins were used for network merging and core network screening,and 69 genes were screened out. Through GO function analysis and KEGG pathway analysis,the mechanism of anti-epilepsy is related to prolactin signaling pathway,HTLV-Ⅰ infection signaling pathway,MAPK signaling pathway and herpes simplex infection signaling pathway. Further experimental verification showed that the serum prolactin level in epileptic rats was significantly increased. The neurons in hippocampal CA1 area degenerated,necrotized and lost 24 hours after epileptic seizure,and some neuron interstitial edema occurred. The possible mechanism of compatibility of Acori Tatarinowii Rhizoma and Curcumae Radix is related to serum prolactin level,MAPK signaling pathway,HTLV-Ⅰ infection and herpes simplex infection. The analysis may be related to viral encephalitis caused by HTLV-Ⅰ virus and herpes simplex infection,which damages nerve cells and causes seizures.
Acorus ; chemistry ; Animals ; CA1 Region, Hippocampal ; drug effects ; pathology ; Curcuma ; chemistry ; Drugs, Chinese Herbal ; pharmacology ; Epilepsy ; drug therapy ; Hippocampus ; Plant Roots ; chemistry ; Rats ; Rhizome ; chemistry

The aim of this paper was to investigate the effect of total saponins from Panax japonicus( SPJ) on cognitive decline of natural aging rats and its mechanism. Thirty male SD rats of eighteen month old were randomly divided into three groups: aged group,10 mg·kg~(-1) SPJ-treated group and 30 mg·kg~(-1) SPJ-treated group. The SPJ-treated groups were given SPJ at the dosages of 10 mg·kg~(-1) and 30 mg·kg~(-1),respectively,from the age of 18 to 24 months. Aged group were lavaged the same amount of saline,10 six-month-old rats were used as control group,with 10 rats in each group. The open field test,novel object recognition and Morris water maze were performed to detect the changes of cognitive function in each group. The changes of synaptic transmission of long-term potentiation( LTP) in hippocampal CA1 region were detected by field potential recording. Western blot was used to detect the protein levels of NLRP3,ASC,caspase-1 and the changes of Glu A1,Glu A2,CAMKⅡ,CREB and phosphorylation of CAMKⅡ,CREB in each group.The results showed that SPJ could improve the decline of cognitive function in aging rats,reduce the damage of LTP in the hippocampal CA1 region of aged rats,and decrease the expression of NLRP3,ASC,caspase-1 in aging rats. At the same time,SPJ could enhance the membrane expression of AMPA receptor( Glu A1 and Glu A2),and increase the expression of p-CAMKⅡand p-CREB in aging rats.SPJ could improve cognitive decline of natural aging rats,and its mechanism may be related to regulating NLRP3 inflammasome,thus regulating the membrane expression of AMPA receptor,and enhancing the expression phosphorylation of CAMKⅡ and CREB.
Aging ; Animals ; CA1 Region, Hippocampal ; physiology ; Cognition ; drug effects ; Inflammasomes ; metabolism ; Long-Term Potentiation ; Male ; NLR Family, Pyrin Domain-Containing 3 Protein ; metabolism ; Panax ; chemistry ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Saponins ; pharmacology

To examine the effects of Populus tomentiglandulosa (PT) extract on the expressions of antioxidant enzymes and neurotrophic factors in the cornu ammonis 1 (CA1) region of the hippocampus at 5 min after inducing transient global cerebral ischemia (TGCI) in gerbils, TGCI was induced by occlusion of common carotid arteries for 5 min. Before ischemic surgery, 200 mg·kg PT extract was orally administrated once daily for 7 d. We performed neuronal nuclear antigen immunohistochemistry and Fluoro-Jade B staining. Furthermore, we determined in situ production of superoxide anion radical, expression levels of SOD1 and SOD2 as antioxidant enzymes and brain-derived neurotrophic factor (BDNF) and insulin-like growth factor I (IGF-I) as neurotrophic factors. Pretreatment with 200 mg·kg PT extract prevented neuronal death (loss). Furthermore, pretreatment with 200 mg·kg PT extract significantly inhibited the production of superoxide anion radical, increased expressions of SODs and maintained expressions of BDNF and IGF-I. Such increased expressions of SODs were maintained in the neurons after IRI. In summary, pretreated PT extract can significantly increase levels of SODs and protect the neurons against TGCI, suggesting that PT can be a useful natural agent to protect against TGCI.
Animals ; Brain-Derived Neurotrophic Factor ; genetics ; metabolism ; CA1 Region, Hippocampal ; drug effects ; metabolism ; Gerbillinae ; Humans ; Insulin-Like Growth Factor I ; genetics ; metabolism ; Male ; Neuroprotective Agents ; administration & dosage ; Plant Extracts ; administration & dosage ; Populus ; chemistry ; Pyramidal Cells ; drug effects ; metabolism ; Reperfusion Injury ; drug therapy ; genetics ; metabolism ; Superoxide Dismutase ; genetics ; metabolism ; Up-Regulation ; drug effects

This paper was aimed to investigate the effect of gastrodin( GAS) on hippocampal neurogenesis after cerebral was chemic and to explore its mechanism of action related to NO. The cerebral ischemia model of C57 BL/6 mice was established by bilateral common carotid artery occlusion. The pathological changes in hippocampal CA1 region and the cognitive function of mice were assessed by HE staining and Morris water maze test,respectively. The count of Brd U/Neu N positive cells in dentate gyrus was detected by immunofluorescence assay. The NOS activity and the NO content were determined by colorimetric and nitrate reduction methods,respectively.The level of c GMP was measured by ELISA kit,and the PKG protein expression was tested by Western blot. On postoperative day 8,the hippocampal CA1 pyramidal neurons of mice showed irregular structure,with obvious nuclear pyknosis,loose cell arrangement and obvious decrease in the number of neurons. On postoperative day 29,the spatial learning ability and memory were decreased. These results indicated cerebral ischemia in mice. Meanwhile,the Brd U/Neu N positive cells were increased significantly in ischemic mice,indicating that neurogenesis occurred in hippocampus after cerebral ischemia. Treatment with different doses of gastrodin( 50 and 100 mg·kg-1) significantly ameliorated the pathological damages in the CA1 region,improved the ability of learning and memory,and promoted hippocampal neurogenesis. At the same time,both the NOS activity and the NO concentration were decreased in model group,but the c GMP level was increased,and the PKG protein expression was up-regulated. Gastrodin administration activated the NOS activity,promoted NO production,further increased c GMP level and up-regulated PKG protein expression. These results suggested that gastrodin can promote hippocampal neurogenesis after cerebral ischemia and improve cognitive function in mice,which may be related to the activation of NO-cGMP-PKG signaling pathway.
Animals ; Benzyl Alcohols/therapeutic use* ; Brain Ischemia/drug therapy* ; CA1 Region, Hippocampal/drug effects* ; Cognition ; Glucosides/therapeutic use* ; Mice ; Mice, Inbred C57BL ; Neurogenesis ; Signal Transduction

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

OBJECTIVETo explore the effect of diallyl disulfide (DADS) on hippocampal synapses and learning and memory abilities in a mouse model of A1zheimer's disease (AD).

METHODSMouse models of AD established by agglutinated Aβ1-42 injection in the lateral cerebral ventricle were randomized into 4 groups and treated with DADS at the daily doses of 0, 10, 50 and 100 mg/kg by gavage for 30 consecutive days. The learning and memory abilities of the mice were assessed with Morris water maze test; the structures of the dendritic spines and synapses in CA1 region of the hippocampus were observed under transmission electron microscope with silver staining; PSD95 and SYP protein and mRNA expressions in the hippocampus were detected with Western blotting and RT-PCR.

RESULTSCompared with the AD model mice, the mice treated with 50 and 100 mg/kg DADS showed enhanced learning and memory abilities in Morris water maze test. The dendritic spines and synapses in CA1 region of the hippocampus increased obviously and hippocampal expressions of PSD95 and SYP were enhanced in mice treated with 50 and 100 mg/kg DADS.

CONCLUSIONDADS at the daily doses of 50 and 100 mg/kg can improve the learning and memory abilities and increase the number of dendritic spines and synapses in the hippocampus in mouse models of AD.

Allyl Compounds ; pharmacology ; Alzheimer Disease ; drug therapy ; Animals ; CA1 Region, Hippocampal ; drug effects ; Disease Models, Animal ; Disulfides ; pharmacology ; Learning ; Male ; Memory ; Mice ; Synapses ; drug effects

BACKGROUNDPropofol and etomidate are the most important intravenous general anesthetics in the current clinical use and that mediate gamma-aminobutyric acid's (GABAergic) synaptic transmission. However, their long-term effects on GABAergic synaptic transmission induced by neonatal propofol or etomidate exposure remain unclear. We investigated the long-term GABAergic neurotransmission alterations, following neonatal propofol and etomidate administration.

METHODSSprague-Dawley rat pups at postnatal days 4-6 were underwent 6-h-long propofol-induced or 5-h-long etomidate-induced anesthesia. We performed whole-cell patch-clamp recording from pyramidal cells in the cornus ammonis 1 area of acute hippocampal slices of postnatal 80-90 days. Spontaneous and miniature inhibitory GABAergic currents (spontaneous inhibitory postsynaptic currents [sIPSCs] and miniature inhibitory postsynaptic currents [mIPSCs]) and their kinetic characters were measured. The glutamatergic tonic effect on inhibitory transmission and the effect of bumetanide on neonatal propofol exposure were also examined.

RESULTSNeonatal propofol exposure significantly increased the frequency of mIPSCs (from 1.87 ± 0.35 Hz to 3.43 ± 0.51 Hz, P< 0.05) and did not affect the amplitude of mIPSCs and sIPSCs. Both propofol and etomidate slowed the decay time of mIPSCs kinetics (168.39 ± 27.91 ms and 267.02 ± 100.08 ms vs. 68.18 ± 12.43 ms; P< 0.05). Bumetanide significantly blocked the frequency increase and reversed the kinetic alteration of mIPSCs induced by neonatal propofol exposure (3.01 ± 0.45 Hz and 94.30 ± 32.56 ms).

CONCLUSIONSNeonatal propofol and etomidate exposure has long-term effects on inhibitory GABAergic transmission. Propofol might act at pre- and post-synaptic GABA receptor A (GABAA) receptors within GABAergic synapses and impairs the glutamatergic tonic input to GABAergic synapses; etomidate might act at the postsynaptic site.

Animals ; CA1 Region, Hippocampal ; drug effects ; metabolism ; Electrophysiology ; Etomidate ; pharmacology ; Hippocampus ; drug effects ; metabolism ; Neurons ; drug effects ; metabolism ; Propofol ; pharmacology ; Rats ; Rats, Sprague-Dawley ; Receptors, GABA-A ; metabolism ; Synaptic Transmission ; drug effects ; gamma-Aminobutyric Acid ; metabolism

OBJECTIVETo observe the effect of Yangxue Qingnao Granule (YQG) on the expression of CD11b in CA1 region of hippocampus of vascular dementia rats, and to explore its regulation on microglias.

METHODSTotally 144 SD rats were randomly divided into the sham-operation group, the vascular dementia model group (model), and the YQG treated group (treated). The vascular dementia rat model was prepared by modified Pulsinelli's four-vessel occlusion. Rats in the sham-operation group and the model group were administered with normal saline -(at the daily dose of 10 mL/kg) by gastrogavage, while those in the treated group were administered with YQG (0.32 g/mL, at the daily dose of 10 mL/kg) by gastrogavage. All administration was performed once per day for 8 successive weeks. The expression of CD11b in CA1 region of hippocampus of vascular dementia rats was detected at week 1, 2, 4, and 8, respectively.

RESULTSCompared with the sham-operation group, the expression of CD11b in CA1 region of hippocampus of vascular dementia rats were significantly enhanced in the model group at each time point (P < 0.01). Compared with the model group, the expression of CD11b in CA1 region of hippocampus of vascular dementia rats significantly decreased in the treated group at each time point (P < 0.01), especially at week 2.

CONCLUSIONObvious activation and proliferation of microglias could be seen in CA1 region of hippocampus of vascular dementia rats, and YQG could inhibit activation and proliferation of microglias.

Animals ; CA1 Region, Hippocampal ; drug effects ; metabolism ; CD11b Antigen ; metabolism ; Dementia, Vascular ; drug therapy ; Disease Models, Animal ; Drugs, Chinese Herbal ; pharmacology ; Microglia ; drug effects ; Random Allocation ; Rats ; Rats, Sprague-Dawley

OBJECTIVETo explore the protection of high intensity microwave radiation on hypothalamo-pituitary-adrenal axis (HPAA) activity and hippocampal CA1 structure in rats and the protectiveeffect of Qindan Granule (QG) on radiation injured rats.

METHODSTotally 48 Wistar rats were randomlydivided into 8 groups, i.e., the normal control group, post-radiation day 1, 7, and 10 groups, 7 and 10days prevention groups, day 7 and 10 treatment groups, 6 in each group. Rats in prevention groups wererespectively administered with QG liquid (1 mL/100 g, 4. 75 g crude drugs) for 7 days and 10 days bygastrogavage and then microwave radiation. Then preventive effect for radiation injury was statisticallycalculated with the normal control group and the post-radiation day 1 group. Rats in treatment groupswere firstly irradiated, and then administered with QG liquid (1 mL/100 g, 4.75 g crude drugs). Finally preventive effect for radiation injury was statistically calculated with the normal control group, post-radiation day 7 and 10 groups. Contents of corticotrophin releasing hormone (CRH), beta endorphin (beta-EP), adrenocorticotropic hormone (ACTH), and heat shock protein 70 (HSP70) were detected. Morphological changes and structure of hippocampal CA1 region were observed under light microscope.

RESULTSCompared with the normal control group, contents of CRH and beta-EP significantly decreased in each radiation group. Serum contents of ACTH and beta-EP significantly increased in post-radiation day 1 and 7 groups (P < 0.05). Compared with radiation groups, beta-EP content in serum and pituitary significantly increased, and serum ACTH content significantly decreased in prevention groups (P < 0.05). Pituitary contents of CRH and beta-EP significantly increased in prevention groups. Serum contents of ACTH, beta-EP, and HSP70 were significantly lower in day 7 treatment group than post-radiation day 7 group (P < 0.05). Morphological results showed that pyramidal neurons in the hippocampal CA1 region arranged in disorder, with swollen cells, shrunken and condensed nucleus, dark dyeing cytoplasm, unclear structure. Vessels in partial regions were dilated with static blood; tissues were swollen and sparse. In prevention and treatment groups pathological damage of hippocampal CA1 region was obviously attenuated; neurons were arranged more regularly; swollen, pycnotic, or deleted neuron number were decreased; vascular dilatation and congestion was lessened.

CONCLUSIONQG could affect HPAA function and activity of high intensity microwave radiated rats, showing certain preventive and therapeutic effects of microwave radiated rats by adjusting synthesis and release of partial bioactive peptides and hormones in HPAA, improving pathological injury in hippocampal CA1 region.

Adrenocorticotropic Hormone ; blood ; Animals ; CA1 Region, Hippocampal ; drug effects ; pathology ; radiation effects ; Corticotropin-Releasing Hormone ; metabolism ; Drugs, Chinese Herbal ; pharmacology ; HSP70 Heat-Shock Proteins ; blood ; Hypothalamo-Hypophyseal System ; drug effects ; radiation effects ; Microwaves ; adverse effects ; Pituitary-Adrenal System ; drug effects ; radiation effects ; Random Allocation ; Rats ; Rats, Wistar ; beta-Endorphin ; blood ; metabolism

OBJETIVETo investigate the neuroprotective effects and underlying mechanisms of salvianolic acid B (Sal B) extracted from Salvia miltiorrhiza on hippocampal CA1 neurons in mice with cerebral ischemia reperfusion injury.

METHODSForty male National Institute of Health (NIH) mice were randomly divided into 4 groups with 10 animals each, including the sham group, the model group, the SalB group (SalB 22.5 mg/kg) and the nimodipine (Nim) group (Nim 1 mg/kg). A mouse model of cerebral ischemia and reperfusion injury was established by bilateral carotid artery occlusion for 30 min followed by 24-h reperfusion. The malondialdehyde (MDA) content, the nitric oxide synthase (NOS) activity, the superoxide dismutase (SOD) activity and total antioxidant capability (T-AOC) of the pallium were determined by biochemistry methods. The morphologic changes and Bcl-2 and Bax protein expression in hippocampal CA1 neurons were observed by using hematoxylineosin staining and immunohistochemistry staining, respectively.

RESULTSIn the SalB group, the MDA content and the NOS activity of the pallium in cerebral ischemia-reperfusion mice significantly decreased and the SOD activity and the T-AOC significantly increased, as compared with the model group (P<0.05 or P<0.01). The SalB treatment also rescued neuronal loss (P<0.01) in the hippocampal CA1 region, strongly promoted Bcl-2 protein expression (P<0.01) and inhibited Bax protein expression (P<0.05).

CONCLUSIONSSalB increases the level of antioxidant substances and decreases free radicals production. Moreover, it also improves Bcl-2 expression and reduces Bax expression. SalB may exert the neuroprotective effect through mitochondria-dependent pathway on hippocampal CA1 neurons in mice with cerebral ischemia and reperfusion injury and suggested that SalB represents a promising candidate for the prevention and treatment of ischemic cerebrovascular disease.

Animals ; Antioxidants ; pharmacology ; therapeutic use ; Benzofurans ; chemistry ; pharmacology ; therapeutic use ; Brain Ischemia ; complications ; drug therapy ; CA1 Region, Hippocampal ; pathology ; Cell Count ; Immunohistochemistry ; Male ; Malondialdehyde ; metabolism ; Mice ; Neurons ; drug effects ; pathology ; Nitric Oxide Synthase ; metabolism ; Reperfusion Injury ; complications ; drug therapy ; Superoxide Dismutase ; metabolism ; bcl-2-Associated X Protein ; metabolism