• Korean Journal of Acupuncture
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• v.22 no.3
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• pp.63-81
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• 2005

Herbal acupuncture has been used to prevent and treat the cerebrovascular accident, such as a stroke, and many studies of acupuncture and moxibustion concerning to the stroke have been undertaken in the human and various animals. The main characteristics of herbal acupuncture are a combination of acupuncture and herbal medicine. It was not well known the therapeutic effect and the mechanism of herbal acupuncture on transient forebrain ischemic injury, although it has been used frequently in clinics. In this study, neuroprotective effects of folium artemisiae argyi (艾葉)' herbal acupuncture on the $LR_3$ (Taechung) on the transient forebrain ischemia were investigated in Sprague-Dawely rats. Expressions of cFos, FosB and BDNF protein in the hippocampus and cortex were observed at 2 hrs and 48 hrs after transient forebrain ischemia by immunohistochemistry and ELISA technique. Expression of cFos protein was increased slightly in the hippocampus and cortex at 2 hrs after transient forebrain ischemia, but FosB protein was increased highly comparing to cFos protein. However, pretreatment with folium artemisiae argyi' herbal acupuncture on $LR_3$ significantly increased expression of cFos protein and significantly decreased expression of FosB protein compared to control group. These features were observed in the motor cortex and retrosplenial granular cortex as well as the hippocampus. Also, pretreatment with folium artemisiae argyi' herbal acupuncture on $LR_3$ significantly increased the expression of BDNF protein in the hippocampus ($263.26{\pm}44.56pg/ml$ extracted by water, $275.35{\pm}51.47pg/ml$ extracted by moxa tar)and the cortex ($102.33{\pm}13.65pg/ml$ extracted by water, $109.54{\pm}9.37pg/ml$ extracted by moxa tar) compared to the hippocampus $(134.07{\pm}2.96pg/ml)$ and the cortex $(61.16{\pm}4.11pg/ml)$ in control group at 48 hrs after transient forebrain ischemia. These results suggest that pretreatment with folium artemisiae argyi'herbal acupuncture on $LR_3$ has neuroprotective effect on transient forebrain ischemia and the herbal acupunture on $LR_3$ may be related to antioxidative function of folium artemisiae argyi.

• The Journal of Internal Korean Medicine
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• v.30 no.4
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• pp.674-684
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• 2009

Objectives : In conditions of brain infarction, irreversible axon damage occurs in the central nerve system (CNS), because gliosis becomes a physical and a mechanical barrier to axonal regeneration. Reactive gliosis induced by ischemic injury such as middle cerebral artery occlusion is involved with up-regulation of GFAP and CD81. This study was undertaken to examine the effect of the Gongjin-dan (GJD) on CD81 and GFAP expression and its pathway in the rat brain following middle cerebral artery occlusion (MCAO). Methods : In order to study ischemic injuries on the brain, infarction was induced by MCAO using insertion of a single nylon thread, through the internal carotid artery, into a middle cerebral artery. Cresyl violet staining, cerebral infarction size measurement, immunohistochemistry and microscopic examination were used to detect the expression of CD81 and GFAP and the effect on the infarct size and pyramidal cell death in the brain of the rat with cerebral infarction induced by MCAO. Also, c-Fos and ERK expression were measured to investigate the signaling pathway after GJD administration in MCAO rats. Results : Measuring the size of cerebral infarction induced by MCAO in the rat after injection of GJD showed the size had decreased. GJD administration showed pyramidal cell death protection in the hippocampus in the MCAO rat. GJD administration decreased GF AP expression in the MCAO rat. GJD administration decreased CD81 expression in the MCAO rat. GJD administration induced up-regulation of c-FOS expression compared with MCAO. GJD administration induced down-regulation of ERK expression compared with MCAO. Conclusion : We observed that GJD could suppress the reactive gliosis, which disturbs the axonal regeneration in the brain of a rat with cerebral infarction after MCAO by controlling the expression of CD81 and GFAP. The effect may be modulated by the regulation of c-Fos and ERK. These results suggest that GJD can be a candidate to regenerate CNS injury.

• The Journal of Korean Medicine
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• v.24 no.2
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• pp.204-212
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• 2003

Current therapy for acute ischemic stroke is highly focused on neuroprotective agents, and many herbal medicines have been challenged for experimental models. The aim of this study is to investigate whether Angelicae gigantis Radix can protect nerve cells against ischemic neural damage of middle cerebral artery occlusion (MCAO) in rats' brains. Rats were treated with Angelicae gigantis Radix immediately after 2 hours of MCAO for 7 days. On the 7th day, the brains of the rats were sliced through the hippocampus and dyedby c-Fos immunohistochemistry stain and cresyl violet stain for microscopic examination. The number of viable neurons and c-Fos immunoreactive cells in CA1 regions was counted. MCAO caused significant decrease in density of neurons and c-Fos immunoreactive cells compared to those of sham-operated rats. Administration of Angelicae gigantis Radix significantly elevated MCAO-induced decrease in density of neurons and c-Fos immunoreactive cells. These results suggest that the neuroprotective effect of Angelicae gigantis Radix against focal cerebral ischemia is related to c-Fos gene expression. Thus, these findings indicate that Angelicae gigantis Radix can be used for treatment and prevention of cerebral ischemia.

• The Korean Journal of Physiology and Pharmacology
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• v.15 no.6
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• pp.437-443
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• 2011

Salt signals in tongue are relayed to the nucleus of the solitary tract (NST). This signaling is very important to determine whether to swallow salt-related nutrition or not and suggests some implications in discrimination of salt concentration. Salt concentration-dependent electrical responses in the chorda tympani and the NST were well reported. But salt concentration-dependency and spatial distribution of c-Fos in the NST were not well established. In the present study, NaCl signaling in the NST was studied in urethane-anesthetized rats. The c-Fos immunoreactivity in the six different NST areas along the rostral-caudal axis and six subregions in each of bilateral NST were compared between applications of distilled water and different concentrations of NaCl to the tongue of experimental animals. From this study, salt stimulation with high concentration (1.0 M NaCl) induced significantly higher c-Fos expression in intermediate NST and dorsal-medial and dorsal-middle subregions of the NST compared to distilled water stimulation. The result represents the specific spatial distribution of salt taste perception in the NST.

• The Korean Journal of Physiology and Pharmacology
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• v.17 no.2
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• pp.121-125
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• 2013

The purpose of this study is to investigate the antinociceptive effects of ginsenosides on toothache. c-Fos immunoreactive (IR) neurons were examined after noxious intrapulpal stimulation (NS) by intrapulpal injection of 2 M KCl into upper and lower incisor pulps exposed by bone cutter in Sprague Dawley rats. The number of Fos-IR neurons was increased in the trigeminal subnucleus caudalis (Vc) and the transitional region between Vc and subnucleus interpolaris (Vi) by NS to tooth. The intradental NS raised arterial blood pressure (BP) and heart rate (HR). The number of Fos-IR neurons was also enhanced in thalamic ventral posteromedial nucleus (VPMN) and centrolateral nucleus (CLN) by NS to tooth. The intradental NS increased the number of Fos-IR neurons in the nucleus tractus solitarius (NTS) and rostral ventrolateral medulla (RVLM), hypothalamic supraoptic nucleus (SON) and paraventricular nucleus (PVN), central cardiovascular regulation centers. Ginsenosides reduced the number of c-Fos-IR increased by NS to tooth in the trigeminal Vc and thalamic VPMN and CLN. Naloxone, an opioid antagonist, did not block the effect of ginsenoside on the number of Fos-IR neurons enhanced by NS to tooth in the trigeminal Vc and thalamic VPMN and CLN. Ginsenosides ameliorated arterial BP and HR raised by NS to tooth and reduced the number of Fos-IR neurons increased by NS to tooth in the NTS, RVLM, hypothalamic SON, and PVN. These results suggest that ginsenosides have an antinociceptive effect on toothache through non-opioid system and attenuates BP and HR increased by NS to tooth.

• The korean journal of orthodontics
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• v.28 no.3 s.68
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• pp.441-452
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• 1998

The c-fos is known as neuronal marker of second neurons which is activated by noxious peripheral stimulation. To investigate the changes of c-fos el(pression in the trigeminal nucleus complex during tooth movement, immunohistochemical study was performed. Experimental rats(9 weeks old, 210 gm 21 rats) were divided into seven groups(normal, 1 hour group, 3 hour group, 6 hour group, 12 hour group, 1 day group,3 day group). Rats in the normal group were anesthesized without orthodontic force. Rats in the experimental groups were applied orthodontic force (approximately 30 gm) to upper right maxillary molar. Frozen sections of brain stem were immunostained using rabbit antisera. The changes of c-fos expression were observed with respect to rostrocaudal distribution, laminar organization, md duration of orthodontic force application. The study results were as follows $\cdot$The c-fos nuclei in the dorsal part were observed from ipsilateral transition zone of subnucleus interpolaris and subnucleus caudalis to $C_1$ cervical dorsal horn rostrocaudally. The maximal peak point was the rostral part of subnucleus caudalis. The greatest proportion of c-fos cells were located within lamina I and II. $\cdot$The c-fos nuclei in the dorsal Part were observed from the most caudal part of subnucleus interpolaris to the middle part of the subnucleus caudalis. $\cdot$The number of c-fos immunoreactive dot increased at 1 hour group, reached its maximum at the 3 and 6 hour groups, and showed a decreasing trend after 12 hours. These results imply that nociceptive stimulation caused by continuous orthodontic force might be modulated by transition zone of subnucleus interpolaris and subnucleus caudalis, subnucleus caudalis, $C_1$ spinal dorsal hem.

• Journal of Acupuncture Research
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• v.26 no.1
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• pp.39-47
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• 2009

Objectives : The mesolimbic dopamine system is believed to play a major role in the reinforcing effect and behavioral hyperactivity of abused drugs including methamphetamine. In the present study, the effect of acupuncture on methamphetamine-induced locomotor activity and c-Fos expression in the striatum and nucleus accumbens of rats were examined. Methods : Male Sprague-Dawley rats received acupuncture at bilateral Yanggu($SI_5$) point for 30seconds immediately before the subcutaneous injection of saline or methamphetamine(0.5mg/kg). The total amount of locomotor activity for 90min were measured just before brain samples were taken for immunohistochemistry. Results : Results showed that acupuncture at the specific point $SI_5$, but not control point(Kunlun, $BL_{60}$) significantly reduced locomotor activity and c-Fos expression in the striatum and nucleus accumbens induced by acute administration of methamphetamine. Conclusions : These results suggest that acupuncture may be effective in suppressing the reinforcing effect of methamphetamine by regulating neuronal activity.

• The Journal of Korean Medicine
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• v.23 no.2
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• pp.97-107
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• 2002

Objective : Acupuncture is a method used to treat many kinds of pain in oriental cultural medicine. Especially when hetero-segmental area acu-points are stimulated, the therapeutic effects of pain control have more critical properties than other methods of acupuncture. However, the mechanism of pain control by acupuncture is contradictory so far. The present study examined the effects of electroacupuncture (EA) applied to the acu-point of the hetero-segmental area on modulation of formalin-induced pain in Sprague-Dawley rats. Methods : In order to apply EA to acu-points in the plantar area of right forepaws, a pair of Teflon-coated stainless steel wires were implanted in HT 7 (Shin-Moon) and PC 7 (Dae-Reung) 7 days before the behavioral test. A behavioral test was performed by means of video camera after injection of 5% formalin ($50{\;}\mu\textrm{l}$) into the lateral plantar region of the left hind paw. EA was delivered by a constant DC current stimulator at 4~5 mA, 2 ms, and 10 Hz for 30 min. c-Fos protein expression was measured in the lumbar spinal cord at 2 hr and 4 hr after formalin injection. Results : Behavioral responses including favoring, flinching and biting occurred in the biphasic pattern, such as the 1st phase (0~5 min) and the 2nd phase (20~45 min) after formalin injection. However, EA (4~5 mA, 2 ms, 10 Hz) significantly inhibited the behavioral responses. Injection of formalin expressed c-Fos protein on the ipsilateral dorsal horn neurons in L3 - L5 and the expression was sustained more than 4 hrs after formalin injection. However, EA decreased c-Fos protein expression at dorsal horn neurons in the lumbar spinal cord till 4hrs after formalin injection. Conclusions : These results suggest that EA modulates formalin-induced pain and this inhibitory action may be elicited by the descending inhibitory system.

• Journal of Korean Medicine Rehabilitation
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• v.21 no.2
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• pp.143-158
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• 2011

Objectives : Peripheral nerve injuries are commonly encountered clinical problem and often result in severe functional deficits. The aim of this study is to evaluate the effects of aqueous extract of Achyranthes japonica(AJ) on functional recovery in sciatic nerve after crushed sciatic nerve injury. Methods : In the present study, the animals in the AJ-treated groups received the aqueous extract of AJ at the respective doses orally for 13 consecutive days. In order to assess the effects of the aqueous extract of AJ on function recovery in crushed sciatic nerve injury, sciatic functional index(SFI) was performed. c-Fos expression in the paraventricular nucleus(PVN) and ventrolateral periaqueductal gray(vIPAG), and neurofilament, and the expressions of brain-derived neurotrophic factor(BDNF), nerve growth factor(NGF) following crushed sciatic nerve injury in rats were investigated. For this, immunohistochemistry and western blot were performed. Results : In the present study, crushed sciatic nerve injury showed characteristic gait changes showing decrease of SFI value and treatment with the aqueous extract of AJ significantly enhanced the SFI value. Neurofilament expression in the sciatic nerve was decreased by crushed sciatic nerve injury and treatment with the AJ increased neurofilament expression. The expressions of BDNF and NGF in the sciatic nerve were increased following crushed sciatic nerve injury and treatment with the AJ significantly controlled the sciatic nerve injury-induced increment of BDNF and NGF expressions. c-Fos expressions in the PVN and vIPAG were increased following crushed sciatic nerve injury and treatment with the AJ significantly suppressed the sciatic nerve injury-induced increment of c-Fos expressions. Conclusions : These results suggest that AJ treatment after crushed sciatic nerve injury is effective in the functional recovery by enhancing axonal regeneration and suppressing of pain.

• The Korean Journal of Physiology and Pharmacology
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• v.19 no.3
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• pp.275-281
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• 2015

Orthostatic hypotension is most common in elderly people, and its prevalence increases with age. Attenuation of the vestibulo-sympathetic reflex (VSR) is commonly associated with orthostatic hypotension. In this study, we investigated the role of glutamate on the vestibulo-solitary projection of the VSR pathway to clarify the pathophysiology of orthostatic hypotension. Blood pressure and expression of both pERK and c-Fos protein were evaluated in the nucleus tractus solitarius (NTS) after microinjection of glutamate into the medial vestibular nucleus (MVN) in conscious rats with sodium nitroprusside (SNP)-induced hypotension that received baroreceptor unloading via sinoaortic denervation (SAD). SNP-induced hypotension increased the expression of both pERK and c-Fos protein in the NTS, which was abolished by pretreatment with glutamate receptor antagonists (MK801 or CNQX) in the MVN. Microinjection of glutamate receptor agonists (NMDA or AMPA) into the MVN increased the expression of both pERK and c-Fos protein in the NTS without causing changes in blood pressure. These results indicate that both NMDA and AMPA receptors play a significant role in the vestibulo-solitary projection of the VSR pathway for maintaining blood pressure, and that glutamatergic transmission in this projection might play a key role in the pathophysiology of orthostatic hypotension.