• Journal of Oriental Neuropsychiatry
• /
• v.21 no.1
• /
• pp.109-124
• /
• 2010

Objectives: This experiment was designed to investigate the effect of the InSamYangYoung-tang(Renshenyangrongtang) extract on $A{\beta}$-induced AD model. Methods: The effects of the InSamYangYoung-tang(Renshenyangrongtang) extract on neural damages of cultured PC12 cells induced by $A{\beta}$ were investigated. The effects of the InSamYangYoung-tang(Renshenyangrongtang) extract on neural damages of hippocampal and cortical neurons in the mouse induced by $\beta$-amyloid were investigated. Results: 1. $A{\beta}$ treatment into neuronal cells activated cell death pathway when analyzed by MTT assay and by histological analysis. Then InSamYangYoung-tang(Renshenyangrongtang) treatment improved cell survival to a similar level as in normal group. 2. $A{\beta}$ treatment increased caspase 3 protein levels but decreased phospho-Erk1/2 in neuronal cells. InSamYangYoung-tang(Renshenyangrongtang) treatment reversed the production levels of two proteins close to those in normal group. 3. $A{\beta}$ treatment induced the atrophy of neuronal cells in terms of neuronal processes and cell body shrinkage, but InSamYangYoung-tang(Renshenyangrongtang) greatly improved their morphology. 4. Neuroprotective activity, as observed in InSamYangYoung-tang(Renshenyangrongtang)-treated groups, was similarly observed in cells treated with galantamine which was used as a positive control. Moreover, overall recovery pattern by InSamYangYoung-tang(Renshenyangrongtang) was similar between cultured PC12 cells and in vivo hippocampal and cerebral cortical neurons in the mouse brain. Conclusions: This experiment shows that the InSamYangYoung-tang(Renshenyangrongtang) may play a protective role in neural tissues damaged by cytotoxic substances. Since neuronal damage seen in degenerative brains such as AD are largely unknown, the current data may provide possible insight into therapeutic strategies for AD treatments. InSamYangYoung-tang(Renshenyangrongtang) might be effective for the treatment of AD. Investigation into the clinical use of the InSamYangYoung-tang(Renshenyangrongtang) for AD is suggested for future research.

• Journal of Korean Neurosurgical Society
• /
• v.29 no.7
• /
• pp.877-885
• /
• 2000

Objective : The NOS inhibitors exhibit antinociceptive activity in rat model of neuropathic pain. NOS activity increases in the dorsal root ganglia(DRG) in neurop-athic pain. However, NOS activity decreases in the dorsal horn of spinal cord in the nerve injury models of neuropathic pain. To investigate whether the mechanism of decrease of NOS expression in the dorsal horn is related to a secondary effect resulting from increased NO production and likewise in the spinal DRG in the spinal nerve ligation model of neuropathic pain. Methods : We conducted behavioral tests for neuropathic pain, and nNOS immunohistochemistry and NADPH-diaphorase histochemistry after tight ligation of the 5th lumbar(L5) and 6th lumbar(L6) spinal nerves and L5 dorsal rhizotomy. Results : Typical neuropathic pain behaviors occurred 7 days after post-ligation in the neuropathic surgery group, but neuropathic pain behaviors in the dorsal rhizotomy group were absent or weak 7 days after post-operation. There was a decrease in the number of nNOS immunoreactive dorsal horn neurons on the both side(especially ipsilateral side) 7 days after post-ligation. The number of nNOS immunoreactive neurons in both side of the dorsal horn was not decreased 7 days after L5 dorsal rhizotomy. Conclusion : These data indicate that the changes in the injured DRG is essential for development and maintenance of neuropathic pain, and mechanism of decrease of nNOS expression in the dorsal horn is a secondary effect against the changes in the DRG including increased NO production in the spinal nerve ligation model of neuropathic pain.

• Journal of Korean Neurosurgical Society
• /
• v.49 no.1
• /
• pp.1-7
• /
• 2011

Objective: Glutamate is a key excitatory neurotransmitter in the brain, and its excessive release plays a key role in the development of neuronal injury. In order to define the effect of nimodipine on glutamate release, we monitored extracellular glutamate release in real-time in a global ischemia rat model with eleven vessel occlusion. Methods: Twelve rats were randomly divided into two groups: the ischemia group and the nimodipine treatment group. The changes of extracellular glutamate level were measured using microdialysis amperometric biosensor, in coincident with cerebral blood flow (CBF) and electroencephalogram. Nimodipine (0.025 ${\mu}g$/100 gm/min) was infused into lateral to the CBF probe, during the ischemic period. Also, we performed Nissl staining method to assess the neuroprotective effect of nimodipine. Results: During the ischemic period, the mean maximum change in glutamate concentration was $133.22{\pm}2.57\;{\mu}M$ in the ischemia group and $75.42{\pm}4.22\;{\mu}M$ (p<0.001) in the group treated with nimodipine. The total amount of glutamate released was significantly different (P<0.001) between groups during the ischemic period. The %cell viability in hippocampus was $47.50{\pm}5.64$ (p<0.005) in ischemia group, compared with sham group. But, the %cell viability in nimodipine treatment group was $95.46{\pm}6.60$ in hippocampus (p<0.005). Conclusion: From the real-time monitoring and Nissl staining results, we suggest that the nimodipine treatment is responsible for the protection of the neuronal cell death through the suppression of extracellular glutamate release in the 11-VO global ischemia model of rat.

• International Journal of Oral Biology
• /
• v.42 no.4
• /
• pp.175-181
• /
• 2017

The aim of this study was to provide a basis for the molecular mechanism underlying the pharmacological action of ethanol. We studied the effects of 1-propanol on the location of n-(9-anthroyloxy)palmitic acid or stearic acid (n-AS) within the phospholipids of synaptosomal plasma membrane vesicles (SPMV). The SPMV were isolated from the bovine cerebral cortex and liposomes of total lipids (SPMVTL) and phospholipids (SPMVPL). 1-Propanol increased the rotational mobility of inner hydrocarbons, while decreasing the mobility of membrane interface, in native and model membranes. The degree of rotational mobility varied with the number of carbon atoms at positions 16, 12, 9, 6 and 2 in the aliphatic chain of phospholipids in the neuronal and model membranes. The sensitivity of increasing or decreasing rotational mobility of hydrocarbon interior or surface by 1-propanol varied with the neuronal and model membranes in the following order: SPMV, SPMVPL and SPMVTL.

• Biomolecules & Therapeutics
• /
• v.28 no.2
• /
• pp.152-162
• /
• 2020

Cerebral ischemia exhibits a multiplicity of pathophysiological mechanisms. During ischemic stroke, the reactive oxygen species (ROS) concentration rises to a peak during reperfusion, possibly underlying neuronal death. Recombinant human erythropoietin (EPO) supplementation is one method of treating neurodegenerative disease by reducing the generation of ROS. We investigated the therapeutic effect of PEGylated EPO (P-EPO) on ischemic stroke. Mice were administered P-EPO (5,000 U/kg) via intravenous injection, and middle cerebral artery occlusion (MCAO) followed by reperfusion was performed to induce in vivo ischemic stroke. P-EPO ameliorated MCAO-induced neurological deficit and reduced behavioral disorder and the infarct area. Moreover, lipid peroxidation, expression of inflammatory proteins (cyclooxygenase-2 and inducible nitric oxide synthase), and cytokine levels in blood were reduced by the P-EPO treatment. In addition, higher activation of nuclear factor kappa B (NF-κB) was found in the brain after MCAO, but NF-κB activation was reduced in the P-EPO-injected group. Treatment with the NF-κB inhibitor PS-1145 (5 mg/kg) abolished the P-EPO-induced reduction of infarct volume, neuronal death, neuroinflammation, and oxidative stress. Moreover, P-EPO was more effective than EPO (5,000 U/kg) and similar to a tissue plasminogen activator (10 mg/kg). An in vitro study revealed that P-EPO (25, 50, and 100 U/mL) treatment protected against rotenone (100 nM)-induced neuronal loss, neuroinflammation, oxidative stress, and NF-κB activity. These results indicate that the administration of P-EPO exerted neuroprotective effects on cerebral ischemia damage through anti-oxidant and anti-inflammatory properties by inhibiting NF-κB activation.

• The Korea Journal of Herbology
• /
• v.21 no.4
• /
• pp.189-195
• /
• 2006

Objectives : It has been reported previously that the roots of Scutellaria baicalensis (known as Huang-Gum in Korean, henceforth referred to as S. baicalensis) could prevent neuronal cell death after global cerebral ischemia. In Genuine Korean medicine, S. baicalensis is known to relieve fever in upper body, and it was thus thought to be able to alleviate deteriorations in brain function. Methods : The protective effects of S. baicalensis against post-stroke memory retardation using 4-vessel occlusion model were examined in the present study. Results : S. baicalensis was shown to significantly alleviate the deficits in learning and memory by increasing the fraction of time spent in the quadrant in which the platform was initially placed ($34.9\;{\pm}\;3.2%$, p < 0.05) compared to that of the ischemia group ($28.0\;{\pm}\;2.5%$). The cytoprotective effect of S. baicalensis on CA1 hippocampal neurons was evaluated by measuring the neuronal cell density. Neuronal cell density in S. baicalensis extracts-treated ischemia group ($138.0\;{\pm}\;13.6\;cells/mm^2$) was significantly increased compared to saline-treated ischemia group ($22.1 \;{\pm}\;9.3\;cells/mm^2$, p < 0.05). In the study of OX-42 immunohistochemistry, S. baicalensis could decrease the micrgial activation in hippocampus after brain ischemia. Conclusion : These results may provide experimental support for the use of S. baicalensis in treating post-stroke memory impairment.

• The Journal of Korean Medicine
• /
• v.24 no.2
• /
• pp.179-192
• /
• 2003

Objectives : Boyanghwanoh-tang (Buyanhaiwu-tang) has been used as a prescription for stroke, senile and vascular dementia, ischemic brain and heart damage in Oriental traditional medicine. However, there is little known about the mechanism by which the water extracts of Boyanghwanoh-tang (Buyanhaiwu-tang) rescue cells fromthese damages, and little is known about the protective mechanisms of Boyanghwanoh-tang (Buyanhaiwu-tang) on oxidative stress in neuronal cells. Therefore, we have investigated the role of Boyanghwanoh-tang (Buyanhaiwu-tang) on serum and glucose deprived apoptosis in PC12 cells. Methods : PC12 Cells have been used extensively as a model for studying the cellular and molecular effects of neuronal cells. The viability of cells was measured by MIT assay. We used DNA fragmentation and caspase 1, 2, 3, 6, 9-likeproteases activation assay. Transcriptional activation of NF-kB was assessed by using electrophoretic mobility shift assay. Results : Boyanghwanoh-tang (Buyanhaiwu-tang) rescued PC12 cells from apoptotic death by serum and glucose deprivation in a dose-dependent manner. The nuclear staining of PC12 cells clearly showed that Boyanghwanoh-tang (Buyanhaiwu-tang) attenuated nuclear condensation and fragmentation, which represent typical neuronal apoptotic characteristics. Boyanghwanoh-tang (Buyanhaiwu-tang) also prevents fragmentation of genomic DNA and activation of caspase 3-like protease in serum and glucose deprived PC12 cells. Furthermore, Boyanghwanoh-tang (Buyanhaiwu-tang) reduced the activation of NF-kB by serum and glucose-deprived apoptosis. Conclusions : These findings suggest that serum and glucose deprivation induces reduced glutathione (GSH) depletion, and consequently, apoptosis through endogenously produced reactive oxygen species in PC12 cells. Also, our data indicated that Boyanghwanoh-tang (Buyanhaiwu-tang) has protective effects against the serum and glucose deprived deaths of PC12 cells, which are mediated by the generation of GSH that, in turn, can reduce oxidative stress caused by reactive oxygen species (ROS) such as hydrogen peroxide.

• The Korean Journal of Physiology and Pharmacology
• /
• v.14 no.5
• /
• pp.279-283
• /
• 2010

Urushinol, a plant allergen, has significantly restricted the medical application of $Rhus$ $verniciflua$, although it has been reported to possess a wide variety of biological activities such as anti-inflammatory, antioxidant, and anti-cancer actions. To reduce the urushinol content while maintaining the beneficial biological activities, mushroom-mediated fermentation of $Rhus$ $verniciflua$ was carried out and this method resulted in significantly attenuated allergenicity [1]. In the present study, to examine the neuroprotective properties of mushroom-fermented stem bark of $Rhus$ $verniciflua$, two constituents were isolated from mushroom-fermented bark and their neuroprotective properties were examined in a mouse model of kainic acid (KA)-induced excitotoxicity. KA resulted in significant apoptotic neuronal cell death in the CA3 region of mouse hippocampus. However, seven daily administrations of RVH-1 or RVH-2 prior to KA injection significantly attenuated KA-induced pyramidal neuronal cell death in the CA3 region. Furthermore, pretreatment with RVH-1 and RVH-2 also suppressed KA-induced microglial activation in the mouse hippocampus. The present study demonstrates that RVH-1 and RVH-2 isolated from $Rhus$ $verniciflua$ and detoxified using mushroom species possess neuroprotective properties against KA-induced excitotoxicity. This leads to the possibility that detoxified $Rhus$ $verniciflua$ can be a valuable asset in herbal medicine.

• Journal of Oriental Neuropsychiatry
• /
• v.20 no.2
• /
• pp.121-131
• /
• 2009

Objectives : From Scrophularia buergeriana water extract(SBW), has been used in vivo test for its beneficial effects on neuronal survival and neuroprotective functions, particularly in connection with APP-related dementias and Alzheimer's disease(AD). $A{\beta}$ oligomer derived from proteolytic processing of the ${\beta}$-amyloid precursor protein(APP), including the amyloid-${\beta}$ peptide($A{\beta}$), play a critical role in the pathogenesis of Alzheimer's dementia. Methods : Using drosophila APP model on APP-induced neuronal cytotoxicity, we demonstrated that SBW prevents neurotoxicity of $A{\beta}$ oligomer, which are the behavior, and possibly causative, feature of AD. We investigated the neuroprotective effects of SBW against the effects of oligomeric $A{\beta}$ and fly behaveior and life span by UAS-GRIM/APP-GAL within transgenic flies. Results and Conclusions : SBW repaired damage leading to the behaveior of APP-induced fly and delayed life span. These results suggest that neuronal damage in AD might be due to two factors: a direct $A{\beta}$ oligomer toxicity and multiple cellular and molecular neuroprotective mechanisms, including attenuation of apoptosis and direct inhibition of $A{\beta}$ oligomer, underlie the neuroprotective effects of SBW.

• IMMUNE NETWORK
• /
• v.11 no.6
• /
• pp.342-347
• /
• 2011

Background: Glial cells are involved in immune and inflammatory responses in the central nervous system (CNS). Glial cells such as microglia and astrocytes also provide structural and functional support for neurons. Migration and morphological changes of CNS cells are associated with their physiological as well as pathological functions. The secreted protein lipocalin-2 (LCN2) has been previously implicated in regulation of diverse cellular processes of glia and neurons, including cell migration and morphology. Methods: Here, we employed a zebrafish model to analyze the role of LCN2 in CNS cell migration and morphology in vivo. In the first part of this study, we examined the indirect effect of LCN2 on cell migration and morphology of microglia, astrocytes, and neurons cultured in vitro. Results: Conditioned media collected from LCN2-treated astrocytes augmented migration of glia and neurons in the Boyden chamber assay. The conditioned media also increased the number of neuronal processes. Next, in order to further understand the role of LCN2 in the CNS in vivo, LCN2 was ectopically expressed in the zebrafish spinal cord. Expression of exogenous LCN2 modulated neuronal cell migration in the spinal cord of zebrafish embryos, supporting the role of LCN2 as a cell migration regulator in the CNS. Conclusion: Thus, LCN2 proteins secreted under diverse conditions may play an important role in CNS immune and inflammatory responses by controlling cell migration and morphology.