• The Journal of Korean Medicine
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• v.30 no.1
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• pp.64-75
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• 2009

Objective: This study was designed to investigate the effect of Samultang (SMT) under hippocampus cells ischemia both in vitro and in vivo. Methods: In the in vitro study, HT22 cells, predominantly detected in the cytoplasm, which coincides with the location of the mitochondria, were used as indicators. In the in vivo study, permanent middle cerebral artery occlusion (MCAO) was induced on rats. SMT was given orally 2 h before induction of permanent focal brain ischemic injury. Result: In the in vitro study, SMT had protective effects in glutamate-induced cytotoxicity, which was revealed as apoptosis characterized by chromatic condensation and the loss of mitochondrial membrane potential in HT22 cells. In the in vivo study, TTC (2,3,5-triphenyltetrazolium chloride) staining showed a marked ischemic injury in blood supply territory of the middle cerebral artery (MCA) such as the cerebral cortex and striatum. However, treatment with SMT significantly reduced infarcted volume. SMT increased marked survival of HT22 cells against glutamate-induced cytotoxicity in MTT assay. Conclusion: These results suggest that water extract of SMT provides neuroprotection against ischemic or oxidative injury by inhibition of apoptotic cell death.

• Journal of Physiology & Pathology in Korean Medicine
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• v.19 no.2
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• pp.416-425
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• 2005

This study demonstrated neuroprotective and anti-oxidative effects of Puerariae Radix for cerebral ischemia. Neuroprotective effects were studied by using oxygen/glucous deprivation of the organotypic hippocampal slice cultures to complement limitations of in vivo and in vitro models for cerebral ischemia study. Anti-oxidative effects were studied on BV-2 microglia cells damaged by $H_2O_2$ and nitric oxide. The results obtained are as follows; The groups treated with 0.5 and $5{\mu}g/m{\ell}$ of Puerariae Radix revealed significant decreases of neuronal cell death area and cell death area percentages in CA1 region of ischemic damaged hippocampus cultures during whole 48 hours of the experiment. The groups treated with 0.5 and $5{\mu}g/m{\ell}$ of Puerariae Radix revealed significant decreases of neuronal cell death area and cell death area percentages in DG region of ischemic damaged hippocampus cultures during whole 48 hours of the experiment. The groups treated with 0.5 and $5{\mu}g/m{\ell}$ of Puerariae Radix revealed significant decreases of TUNEL-positive cells in both CA1 region and DG region of ischemic damaged hippocampus cultures. The group treated with $50\;{\mu}g/m{\ell}$ of Puerariae Radix demonstrated significant decrease of TUNEL-positive cells in CA1 region. The groups treated with 0.5 and $5{\mu}g/m{\ell}$ of Puerariae Radix revealed significant decreases of LDH concentrations in culture media of ischemic damaged hippocampus cultures. The groups treated with 0.5 and $5{\mu}g/m{\ell}$ of Puerariae Radix revealed significant increases of cell viabilities of BV-2 microglia cells damaged by $H_2O_2$. The group treated with $5{\mu}g/m{\ell}$ of Puerariae Radix revealed significant increase of cell viability of BV-2 microglia cells damaged by nitric oxide. These results suggested that Puerariae Radix of cerebral ischemic revealed neuroprotective effects through the control effect of apoptosis and oxidative damages.

• The Korean Journal of Physiology and Pharmacology
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• v.17 no.1
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• pp.15-21
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• 2013

Aspirin (acetylsalicylic acid) is one of the most widely used therapeutic agents based on its pharmacological actions, including anti-inflammatory, analgesic, anti-pyretic, and anti-thrombotic effects. In this study, we investigated the effects of aspirin on seizure susceptibility and hippocampal neuropathology following pilocarpine-induced status epilepticus (SE). SE was induced by pilocarpine hydrochloride (280 mg/kg, i.p.) administration in C57BL/6 mice (aged 8 weeks). Aspirin was administered daily (15 mg/kg or 150 mg/kg, i.p.) for 10 days starting 3 days before SE, continuing until 6 days after SE. After pilocarpine injection, SE onset time and mortality were recorded. Neuronal cell death was examined using cresyl violet and Fluoro-Jade staining, and glial responses were observed 7 days post SE using immunohistochemistry. In the aspirin-treated group, the onset time of SE was significantly shortened and mortality was markedly increased compared to the control group. However, in this study, aspirin treatment did not affect SE-induced neuronal cell death or astroglial and microglial responses in the hippocampus. In conclusion, these results suggest that the safety of aspirin should be reevaluated in some patients, especially with neurological disorders such as temporal lobe epilepsy.

• Journal of Oriental Neuropsychiatry
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• v.18 no.3
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• pp.55-82
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• 2007

Ohjective: This research investigates the effect of the DJR on Alzheimer's disease. Method: 1.The effects of the DJR extract on IL.-$1{\beta}$, IL-6, TNF-${\alpha}$, cox-2, and NOS-II mRNA of BV2 microglia cell line treated with LPS; 2. the behavior: 3. the infarction area of the hippocampus, and brain tissue injury in Alzheimer's diseased mice induced with ${\beta}$A were investigated. Result: 1. The DJR extract suppressed the expression of IL-$1{\beta}$, IL-6 and TNF-${\alpha}$ mRNA in BV2 microglia cell line treated with LPS. 2. The DJR extract suppressed the expression of IL-$1{\beta}$, IL-6, and TNF-${\alpha}$ protein production in BV2 microglia cell line treated with LPS. 3. For the DJR extract group a significant inhibitory effect on the memory deficit was shown for the mice with Alzheimer's disease induced by .${\beta}$A in the Moms water maze experiment, which measured stop-through latency, and distance movement-through latency. 4. The DJR extract suppressed the over-expression of IL-$1{\beta}$ protein, TNF-${\alpha}$ protein and CD68/CD11b, in the mice with Alzheimer's disease induced by ${\beta}$A 5. The DJR extract reduced the infarction area of hippocampus, and controlled the injury of brain tissue in the mice with Alzheimer's disease induced by ${\beta}$A. 6. The DJR extract reduced the tau protein, GFAP protein, and presenilin1/2 protein (immunohistochemistry) of hippocampus in the mice with Alzheimer's disease induced by ${\beta}$A. Conclusion: These results suggest that the DJR extract may he effective for the prevention and treatment of Alzheimer's disease. Investigation into the clinical use of the DJR extract for Alzheimer's disease of suggested for future research.

• Journal of Ginseng Research
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• v.47 no.3
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• pp.390-399
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• 2023

Background: Gintonin (GT), a Panax ginseng-derived lysophosphatidic acid receptor (LPAR) ligand, has positive effects in cultured or animal models for Parkinson's disease, Huntington's disease, and so on. However, the potential therapeutic value of GT in treating epilepsy has not yet been reported. Methods: Effects of GT on epileptic seizure (seizure) in kainic acid [KA, 55mg/kg, intraperitoneal (i.p.)]-induced model of mice, excitotoxic (hippocampal) cell death in KA [0.2 ㎍, intracerebroventricular (i.c.v.)]-induced model of mice, and levels of proinflammatory mediators in lipopolysaccharide (LPS)-induced BV2 cells were investigated. Results: An i.p. injection of KA into mice produced typical seizure. However, it was significantly alleviated by oral administration of GT in a dose-dependent manner. An i.c.v. injection of KA produced typical hippocampal cell death, whereas it was significantly ameliorated by administration of GT, which was related to reduced levels of neuroglial (microglia and astrocyte) activation and proinflammatory cytokines/enzymes expression as well as increased level of the Nrf2-antioxidant response via the upregulation of LPAR 1/3 in the hippocampus. However, these positive effects of GT were neutralized by an i.p. injection of Ki16425, an antagonist of LPA1-3. GT also reduced protein expression level of inducible nitric-oxide synthase, a representative proinflammatory enzyme, in LPS-induced BV2 cells. Treatment with conditioned medium clearly reduced cultured HT-22 cell death. Conclusion: Taken together, these results suggest that GT may suppress KA-induced seizures and excitotoxic events in the hippocampus through its anti-inflammatory and antioxidant activities by activating LPA signaling. Thus, GT has a therapeutic potential to treat epilepsy.

• Journal of Physiology & Pathology in Korean Medicine
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• v.33 no.1
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• pp.10-16
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• 2019

In order to investigate the effects of Eucomiae Cortex extracts on the depression caused by aging, histochemistry and immunohistochemistry were performed on the hippocampus of aged rats and the following results were obtained. Experimental animals were divided into three groups as follows: 8 week old ICR male mice, Aging-elicited group (AE group) and Eucomiae Cortex treatment group (EC group) 50 week old male ICR mice were used. The control group and AE group did not take any treatment and did not restrict diets and negatives. In the EC group, 0.51g/kg of Eucomiae Cortex extract was dissolved in distilled water once a day for 6 months. The Eucomiae Cortex extract reduced pyramidal neuronal damage in C3 hippocampus and dentate gyrus, increased DJ-1, SHH positive responses in aged mouse hippocampus, and 8-OHdG positivity was reduced, ${\beta}$-endorphin positivity was reduced in aged mouse substantia nigra. Therefore, based on the above results, Eucomiae Cortex extract reduces damage of pyramidal neurons in the hippocampus caused by aging, inhibits neuronal cell death, induces proliferation and differentiation of stem cells in the hippocampus, reduces DNA damage-induced oxidative stress, so improves the reduction of hippocampus volume. It is also thought to improves depression due to aging through ${\beta}$-endorphin which enhances mood through the inhibition of pain.

• The Korean Journal of Physiology and Pharmacology
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• v.8 no.2
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• pp.77-81
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• 2004

The loss of neurons and synaptic contacts following cerebral ischemia may lead to a synaptic plastic modification, which may contribute to the functional recovery after a brain lesion. Using synapsin I and GAP-43 as markers, we investigated the neuronal cell death and the synaptic plastic modification in the rat hippocampus of a middle cerebral artery occlusion (MCAO) model. Cresyl violet staining revealed that neuronal cell damage occurred after 2 h of MCAO, which progressed during reperfusion for 2 weeks. The immunoreactivity of synapsin I and GAP-43 was increased in the stratum lucidum in the CA3 subfield as well as in the inner and outer molecular layers of dentate gyrus in the hippocampus at reperfusion for 2 weeks. The immunoreactivity of phosphosynapsin was increased in the stratum lucidum in the CA3 subfield during reperfusion for 1 week. Our data suggest that the increase in the synapsin I and GAP-43 immunoreactivity probably mediates either the functional adaptation of the neurons through reactive synaptogenesis from the pre-existing presynaptic nerve terminals or the structural remodeling of their axonal connections in the areas with ischemic loss of target cells. Furthermore, phosphosynapsin may play some role in the synaptic plastic adaptations before or during reactive synaptogenesis after the MCAO.

• Korean Journal of Biological Psychiatry
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• v.7 no.2
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• pp.164-173
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• 2000

This study was carried out to investigate the direct neurotoxicity of alcohol on CNS and the effects of piracetam or vitamins on ultrastructural changes of the rat cerebellar and hippocampal neurons during long-term alcohol treatment. To evaluate the results, quantitative analysis were done for light and electronic microscopic findings. On the light microscopy, red degeneration of pyramidal cells and Purkinje cells was found more apparently in the alcohol only treated group than in the control group. On the electron microscopy, increased lipofuscin pigments were found in cerebellum and hippocampus. In quantitative analysis, vitamins significantly reduced red degeneration in both hippocampus and cerebellum. However, piracetam significantly reduced red degeneration in cerebellum but not in hippocampus. Lipofuscin pigments in Purkinje cells and pyramidal cells were significantly reduced in the alcohol with piracetam treated group than the alcohol only treated group. However, vitamins had no significant reducing effect of lipofuscin pigments in Purkinje cells and pyramidal cells. According to the results, it is concluded that vitamins deficiency might cause red degeneration of pyramidal cell after long-term alcohol treatment, but increment of lipofuscin pigments in pyramidal and Purkinje cell may be caused by alcohol itself or its metabolite rather than vitamins deficiency. Piracetam seems to improve cognitive function impairment caused by alcohol consumption.

• The Korean Journal of Physiology and Pharmacology
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• v.10 no.4
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• pp.167-172
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• 2006

In the present study, we developed a simple method to predict the neuronal cell death in the mouse hippocampus and striatum following transient global forebrain ischemia by evaluating both cerebral blood flow and the plasticity of the posterior communicating artery (PcomA). Male C57BL/6 mice were anesthetized with halothane and subjected to bilateral occlusion of the common carotid artery (BCCAO) for 30 min. The regional cerebral blood flow (rCBF) was measured by laser Doppler flowmetry. The plasticity of PcomA was visualized by intravascular perfusion of India ink solution. When animals had the residual cortical microperfusion less than 15% as well as the smaller PcomA whose diameter was less than one third compared with that of basilar artery, neuronal damage in the hippocampal subfields including CA1, CA2, and CA4, and in the striatum was consistently observed. Especially, when mice met these two criteria, marked neuronal damage was observed in CA2 subfield of the hippocampus. In contrast, after transient BCCAO, neuronal damage was consistently produced in the striatum, dependent more on the degree of rCBF reduction than on the plasticity of PcomA. The present study provided simple and highly reproducible criteria to induce the neuronal cell death in the vulnerable mice brain areas including the hippocampus and striatum after transient global forebrain ischemia.

• Journal of Physiology & Pathology in Korean Medicine
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• v.19 no.5
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• pp.1303-1310
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• 2005

This study was performed to investigate the effect of Bunsimgieumgagam on the stress due to the maternal separation in rat. In this study, we researched in 'the behavioral observation', 'the changes of body weight', 'quantitative analysis of the number of BrdU-positive cells per section in dentate gyrus of hippocampus', 'free radical scavenging assay' and 'MTT-based cytotoxicity assay of SK-N-SH cell line', in order to figure out the effect on which Bunsimgieumgagam has the increase of neuron in dentate gyrus of hippocampus damaged by the stress due to the maternal separation. In the behavioral Observation, Bunsimgieumgagam was also efficacious against the decline of one's behavior and anorexia derived from the stress by the maternal separation. In the change of body weight, it showed that the Bunsimgieumgagam is effective in the recovery of weight loss caused by heavy stress(p<0.05). Also, Bunsimgieumgagam had an increasing effect, which is similar to a normal state, on DG's neuron in hippocampus (P<0.001). In free radical scavenging assay, Bunsimgieumgagam had a superior free radical scavenging effect. And it showed a significant result with the high cell proliferation effect in MTT-based cytotoxicity assay(P<0.01, p<0.001) This result suggest that Bunsimgieumgagam has an anti-stress effect and a proliferation effect of neuron in dentate gyrus of hippocampus, and it shows the potential of Bunsimgieumgagam in the treatment for the various disorders derived from children's stress.