• Journal of Korean Neurosurgical Society
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• v.29 no.10
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• pp.1296-1302
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• 2000

Objective : Traumatic brain injury including diffuse axonal injury has been shown to result in a decrease in brainfree magnesium concentration, an endogenous inhibitor of calcium entry into neuron, that is associated with the development of neurological motor deficits. The goal of this study is to establish the therapeutic window during which the therapy with $MgSO_4$ and/or hypothermia improve damaged neurons by TUNEL stain. Method : Moderate brain injury was induced in 64 adult Sprague-Dawley rats, weighing 350 to 450gm each, by using a simple weight-drop device(Marmarou model). The animals were randomly assigned to four groups(sixteen rats each, a control group, a group treated with $MgSO_4$, a group treated with hypothermia, and a group treated with $MgSO_4$ and hypothermia) and the rats in each group were sacrificed and studied after 12 hrs, 24 hrs, 1 wk, and 2 wks after insult. In hypothermic group, these rats were subjected to hypothermia after injury, with their rectal temperatures maintained at $32^{\circ}C$ for 1 hour. After 1-hour period of hypothermia, rewarming to normothermic level was accomplished over 30-minute period. In the groups treated $MgSO_4$, hypothermia and $MgSO_4$ were subsequently treated with $MgSO_4$($750{\mu}moles/kg$) infused intra-muscularly at 30 minutes after trauma. Result : In all treated groups, a significant reduction in TUNEL positive cells was found in comparison with the control group each time(p<0.001). Between treatment groups, No differnce was seen 12hrs, 24hrs, and 1wk. However, hypothermic group treated with or without $MgSO_4$ showed more significant reduction in apoptotic cells than group treated with $MgSO_4$ 2 weeks after trauma(p<0.05). However, hypothermic group treated with $MgSO_4$ showed no significant reduction in apoptotic cells compared with hypothermic group(p>0.05). Conclusion : These findings suggest that both hypothermia and $MgSO_4$ significantly improve pathological changes. Otherwise simultaneously $MgSO_4$ and hypothermia treatment groups is failed to provide additional neuroprotection. These results may be relevant to the design of future clinical trials of therapeutic hypothermia and $MgSO_4$ for traumatic brain injury.

• Journal of Acupuncture Research
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• v.29 no.5
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• pp.187-195
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• 2012

Objectives : Amyotrophic lateral sclerosis(ALS) is a progressive and incurable disease that causes degeneration of the motor neurons of the brain stem and spinal cord. The purpose of this study was to report the effectiveness of Sa-am acupuncture treatment on ALS patient. Methods : Following the stabilization period, a ALS patient respiratory figures(Et $C_{O2}$, Sp $_{O2}$, RR, pulse) were measured by using capnography & pulse oximetry for 30 minutes before acupuncture treatment. Acupuncture treatment such as lung tonification($SP_3(+){\cdot}LU_9(+){\cdot}HT_8(-){\cdot}LU_{10}(-)$), heart tonification($HT_9(+){\cdot}LR_1(+){\cdot}SI_8(-){\cdot}KI_{10}(-)$), liver tonification ($KI_{10}(+){\cdot}LR_8(+){\cdot}LU_8(-){\cdot}LR_4(-)$) were conducted for 5 days. Each Sa-am acupuncture treatment conducted at AM 7 : 00, AM 11 : 00, PM 4 : 30 of the day. During acupuncture treatment, the patient respiratory figures were measured equally for 30 minutes. The patient was treated by using Dong-bang acupuncture needles($0.30{\times}4.0$) and also stimulated using infra red. Results : The value of Et $C_{O2}$ has decreased more after Sa-am acupuncture lung tonification treatment than others. The value of pulse has decreased more after Sa-am acupuncture heart tonification treatment than others. The value of raspiration rate has decreased more after Sa-am acupuncture liver tonification treatment than others. And the value of Sp $O_2$ has increased more after Sa-am acupuncture liver tonification treatment than others. Conclusions : Although this study was subject to a few limitations, but it shows that Sa-am acupuncture treatment for ALS patients has a meaningful effect. This study needs to be developed further using a larger sample size to obtain more valuable and meaningful data.

• Molecules and Cells
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• v.43 no.4
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• pp.360-372
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• 2020

The basal ganglia network has been implicated in the control of adaptive behavior, possibly by integrating motor learning and motivational processes. Both positive and negative reinforcement appear to shape our behavioral adaptation by modulating the function of the basal ganglia. Here, we examined a transgenic mouse line (G2CT) in which synaptic transmissions onto the medium spiny neurons (MSNs) of the basal ganglia are depressed. We found that the level of collaterals from direct pathway MSNs in the external segment of the globus pallidus (GPe) ('bridging collaterals') was decreased in these mice, and this was accompanied by behavioral inhibition under stress. Furthermore, additional manipulations that could further decrease or restore the level of the bridging collaterals resulted in an increase in behavioral inhibition or active behavior in the G2CT mice, respectively. Collectively, our data indicate that the striatum of the basal ganglia network integrates negative emotions and controls appropriate coping responses in which the bridging collateral connections in the GPe play a critical regulatory role.

• The Journal of Pediatrics of Korean Medicine
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• v.15 no.1
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• pp.77-104
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• 2001

The effects of the oriental herbal medicine Saenghyetang(SHT, 生慧湯), which consists of Rehmanniae Radix (熟地黃 九蒸: was made by 9th steam) 40g, Corni Fructus(山茱黃) 16g, Polygalae Radix(遠志) 8g, Zizyphi Spinosae Semen(酸棗仁) 2g, Biotae Semen(柏子仁 去油: oil ingredient was removed) 20g, Poria Cocos(茯笭) 12g, Ginseng Radix(人蔘) 12g, Acori Graminei Rhizoma(石菖蒲) 2g, Sinapis Semen(白芥子) 8g, on learning ability and memory were investigated. Hot water extract(HWE) and ethanol extract(EE) from SHT were used for the studies. Learning ability and memory are related to modifications of synaptic strength among neurons that interactive. Enhanced synaptic coincidence detection leads to improved learning ability and memory. If the NMDA receptor, a synaptic coincidence detector, acts as a graded switch for memory formations, enhanced signal detection by NMDA receptors should enhance learning ability and memory. It was shown that NR2B was increased in the forebrains of oriental medicine-administrated mice, leading to enhanced activation of NMDA receptors and facilitating synaptic potentiation in response to stimulation at 10-100 Hz. These HWE-SHT treated mice exhibited that superior ability in learning and memory when performing various behavioral tasks, showing that NR2B is enhanced by HWE-SHT treatment and also is critical in gating the age-dependent threshold for plasticity and memory formation. NMDA receptor-dependent modifications, which were mediated in part by HWE administration, of synaptic efficacy, therefore, represent a mechanism for associative learning ability and memory. Results suggest that oriental medical enhancement of NR2B contributes to increase intelligence and memory in mammals On the other hand, to examine the effects of EE-SHT on the learning ability and memory in experimental mice, EE-SHT was tested on passive and active avoidance responses. The EE-SHT ameliorated the memory retrieval deficit induced by ethanol in mice, but not other memory impairments. EE-SHT(10, 20mg/100 g, p.o.) did not affect the passive avoidance responses of normal mice in the step through and step down tests, the conditioned and unconditioned avoidance responses of normal mice in the shuttle box, lever press performance tests and the ambulatory activity of normal mice in a normal condition. However, EE-SHT at 20 mg/kg significantly decrease the spontaneous motor activity during the shuttle box test, and also to extend the sleeping time induced by pentobarbital in mice. These results suggest that SHT has an ameliorating effect on memory retrieval impairments and a weak tranquilizing action.

• Journal of Life Science
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• v.29 no.2
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• pp.191-197
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• 2019

Parkinson's disease (PD) is a progressive neurodegenerative disease that mainly affects motor system with clinical features such as bradykinesia, rigidity, tremor and abnormal posture. PD is characterized by the death of dopaminergic neurons in the substantia nigra pars compacta, which is associated with accumulation of oxidative stress and dysregulation of intracellular signaling pathway. Quercetin-3-O-glucuronide (Q3GA), a major metabolite of quercetin, has been reported to have neuroprotective effects. In this study, we examined the neuroprotective effect of Q3GA against 1-methyl-4-phenyl pyridinium ($MPP^+$)-induced neurotoxicity of PD and the underlying molecular mechanisms in SH-SY5Y cells. MTT and LDH assay showed that Q3GA significantly decreased $MPP^+$-induced cell death, which is accompanied by a reduction in poly (ADP-ribose) polymerase (PARP) cleavage. Furthermore, it attenuated $MPP^+$-induced intracellular reactive oxygen species (ROS) with the reduction of Bax/ Bcl-2 ratio. Moreover, Q3GA significantly increased the phosphorylation of Akt and cAMP response element binding protein (CREB), but it has no effects on the phosphorylation of extracellular signal-regulated kinase (ERK). Taken together, these results demonstrate that Q3GA significantly attenuates $MPP^+$-induced neurotoxicity through ROS reduction and Akt/CREB signaling pathway in SH-SY5Y cells. Our findings suggest that Q3GA might be one of the potential candidates for the prevention and/or treatment of PD.

• Molecules and Cells
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• v.45 no.3
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• pp.134-147
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• 2022

The anti-oxidant enzyme heme oxygenase-1 (HO-1) is known to exert anti-inflammatory effects. From a library of pyrazolo[3,4-d]pyrimidines, we identified a novel compound KKC080096 that upregulated HO-1 at the mRNA and protein levels in microglial BV-2 cells. KKC080096 exhibited anti-inflammatory effects via suppressing nitric oxide, interleukin1β (IL-1β), and iNOS production in lipopolysaccharide (LPS)-challenged cells. It inhibited the phosphorylation of IKK and MAP kinases (p38, JNK, ERK), which trigger inflammatory signaling, and whose activities are inhibited by HO-1. Further, KKC080096 upregulated anti-inflammatory marker (Arg1, YM1, CD206, IL-10, transforming growth factor-β [TGF-β]) expression. In 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridinetreated mice, KKC080096 lowered microglial activation, protected the nigral dopaminergic neurons, and nigral damage-associated motor deficits. Next, we elucidated the mechanisms by which KKC080096 upregulated HO-1. KKC080096 induced the phosphorylation of AMPK and its known upstream kinases LKB1 and CaMKKbeta, and pharmacological inhibition of AMPK activity reduced the effects of KKC080096 on HO-1 expression and LPS-induced NO generation, suggesting that KKC080096-induced HO-1 upregulation involves LKB1/AMPK and CaMKKbeta/AMPK pathway activation. Further, KKC080096 caused an increase in cellular Nrf2 level, bound to Keap1 (Nrf2 inhibitor protein) with high affinity, and blocked Keap1-Nrf2 interaction. This Nrf2 activation resulted in concurrent induction of HO-1 and other Nrf2-targeted antioxidant enzymes in BV-2 and in dopaminergic CATH.a cells. These results indicate that KKC080096 is a potential therapeutic for oxidative stress-and inflammation-related neurodegenerative disorders such as Parkinson's disease.