Seong-Uk Park

ANTI-INFLAMMATORY EFFECTS OF CROCIN AND CROCETIN IN RAT BRAIN MICROGLIAL CELLS

Microglial cells play critical roles in the immune and inflammatory responses of the central nervous system (CNS). Under pathological conditions, the activation of microglia helps in restoring CNS homeostasis. However, chronic microglial activation endangers neuronal survival through the release of various proinflammatory and neurotoxic factors. Thus, negative regulators of microglial activation have been considered as potential therapeutic candidates to target neurodegeneration, such as that observed in Alzheimers and Parkinsons diseases. Crocin and crocetin, found in the fruits of gardenia and in the stigmas of saffron, have been considered for the treatment of various disorders in traditional oriental medicine. Crocin and crocetin have been reported to have diverse pharmacological functions, such as anti-hyperlipidemic, anti-atherosclerotic, and anti-cancer effects. Specifically, the neuroprotective potential of crocetin derivatives has previously been demonstrated. The specific aim of this study was to examine whether crocin or crocetin represses microglial activation. Crocin and crocetin were shown to be effective in the inhibition of LPS-induced nitric oxide (NO) release from cultured rat brain microglial cells. These compounds reduced the LPS-stimulated productions of tumor necrosis factor-α, interleukin-1β, and intracellular reactive oxygen species. The compounds also effectively reduced LPS-elicited NF-κB activation. In addition, crocin reduced NO release from microglia stimulated with interferon-γ and amyloid-β. In organotypic hippocampal slice cultures, both crocin and crocetin blocked the effect of LPS on hippocampal cell death. These results suggest that crocin and crocetin provide neuroprotection by reducing the production of various neurotoxic molecules from activated microglia.

An fMRI study of neuronal specificity of an acupoint: electroacupuncture stimulation of Yanglingquan (GB34) and its sham point.

The neuronal specificity of acupoints has not been entirely supported by the results of fMRI studies. The objective of this study was to investigate the neuronal specificity of an acupoint with electroacupuncture stimulation (EAS) using functional magnetic resonance imaging (fMRI). Functional MR imaging of the entire brain was performed in 12 normal healthy subjects during EAS of GB34 (Yanglingquan) and its sham point over the left leg in counter-balanced order. Anatomically, both GB34 and its sham point belong to the L5 spinal segment. EAS at the left GB34 specifically activated the right putamen, caudate body, claustrum, thalamus, cerebellum, as well as the left caudate body, ventral lateral thalamus, and cerebellum, all related to motor function. EAS at the sham point of the left GB34 specifically activated the right BA6, BA8, BA40, BA44, thalamus, as well as the left thalamus and cerebellum. Taken together, these findings suggest that EAS at an acupoint and its sham point, in the same spinal segment, induced specific cerebral response patterns. These findings support neuronal specificity of the acupoint studied. EAS at GB34 appears to be more related to motor function than EAS at its sham point, suggesting specificity of the GB34 acupoint. The results of this study provide neurobiological evidence for the existence of acupoint specificity, although further studies are necessary to better understand this phenomenon.

The Acute Effect of Acupuncture on Endothelial Dysfunction in Patients with Hypertension: A Pilot, Randomized, Double-Blind, Placebo-Controlled Crossover Trial

OBJECTIVES The objective of the study was to test whether acupuncture improves endothelial dysfunction in patients with hypertension and compare the effects of different acupoints to find out which one is the most suitable for the long-term follow-up study. DESIGN This study is a pilot, randomized, double-blind, placebo-controlled crossover trial. Subjects were randomly assigned to a sequence of four acupuncture treatment phases, each for 15 minutes with a 7-day washout period in between. Acupuncture needles were inserted at bilateral ST 36; PC 6; ST 36 plus PC 6; and placebo points. SUBJECTS Fifteen (15) patients with essential hypertension were the subjects. OUTCOME MEASURES Flow-mediated dilation (FMD) and blood pressure were assessed before and after acupuncture treatment. RESULTS FMD significantly improved with the acupuncture treatment at ST 36 (0.266 +/- 0.078 mm to 0.306 +/- 0.077 mm, p = 0.003) and ST 36 plus PC 6 (0.284 +/- 0.098 mm to 0.332 +/- 0.103 mm, p < 0.001). In contrast, FMD was unchanged after the acupuncture treatment at PC 6 or the placebo treatment. The FMD response to the acupuncture treatment at ST 36 plus PC 6 was significantly different from the response to the acupuncture treatment at PC 6 and the placebo treatment (p < 0.05, p < 0.01, respectively). The acupuncture treatment at ST 36 significantly increased FMD compared to the placebo treatment (p < 0.05). CONCLUSIONS This study demonstrates that the acute treatment of acupuncture in hypertensive patients improves endothelial dysfunction. The beneficial effect of acupuncture could be of clinical importance to prevent the progression of cardiovascular diseases in hypertensive patients. However, the potential role of acupuncture treatment for long-term therapy has not been examined. Further studies will be necessary to demonstrate whether long-term acupuncture treatment can sustain the improvement in endothelial dysfunction.

fMRI study of effect on brain activity according to stimulation method at LI11, ST36-painful pressure and acupuncture stimulation of same acupoints

OBJECTIVES The objective of this study was to assess differences in brain responses between pressure and acupuncture stimulation at the same acupoint using functional magnetic resonance imaging (fMRI). SUBJECTS A total of 10 healthy right-handed volunteers were studied. DESIGN fMRI was performed with two different paradigms; namely, pressure and acupuncture stimulation at acupuncture points LI11 and ST36 on the left. fMRI data were analyzed using SPM2. RESULTS In comparison with the left LI11 pressure stimulation, both sides of the parahippocampal gyrus, cerebellum, left side of thalamus, and right side of posterior cingulate regions were more activated by the left LI11 acupuncture stimulation. In comparison with the left ST36 pressure stimulation, the secondary motor cortex, limbic system (cingulate gyrus, posterior cingulate), primary visual cortex, pons, and medulla regions were more activated by left ST36 acupuncture stimulation. In comparison with the left ST36 pressure stimulation, both side of BA 4 and BA 6 were more activated by the LI11 pressure stimulation. In comparison with the left LI11 acupuncture stimulation, left BA 6, BA 8, and anterior cingulate cortex (ACC) were more activated by the left ST36 acupuncture stimulation. CONCLUSIONS In conclusion, brain signal activation patterns according to the stimulation methods and acupoints were observed to differ. Acupuncture stimulation activated more regions than pressure at the same acupoint. In particular, acupuncture stimulation activated the limbic system, such as the parahippocampal gyrus and ACC.

Bee venom acupuncture point injection for central post stroke pain: A preliminary single-blind randomized controlled trial

OBJECTIVE We investigated apipuncture, or acupuncture point injection with diluted bee venom, as a promising new treatment for central post stroke pain (CPSP). METHODS Bee venom, diluted to 0.005% in normal saline, was administered to the treatment group, and normal saline given to control group as twice-weekly injections for three weeks. The points were LI15, GB21, LI11, GB31, ST36 and GB39 of the affected side and the amount of injection was 0.05 ml at each point. RESULTS Eight patients in each group were included in the analysis. After three weeks there were significant decreases in visual analogue pain scores compared with baseline in both groups and the treatment group improved more significantly than the control group (p = 0.009). CONCLUSION Apipuncture significantly improved CPSP in this pilot trial. Further studies of its mechanisms and a larger and long-term follow-up trial will be needed to determine more definitely the efficacy of apipuncture and to elucidate duration of improvement.

Effects of Scalp Acupuncture Versus Upper and Lower Limb Acupuncture on Signal Activation of Blood Oxygen Level Dependent (BOLD) fMRI of the Brain and Somatosensory Cortex

OBJECTIVE The objective of this article is to investigate brain activity of scalp acupuncture (SA) as compared to upper and lower limb acupuncture (ULLA) using functional magnetic resonance imaging (fMRI). SUBJECTS AND METHODS Ten (10) healthy right-handed female volunteers aged 20-35 were divided into 2 groups: a SA group and an ULLA group. The SA group had needles inserted at the left Sishencong (HN1), GB18, GB9, TH20, and the ULLA group at the right LI1, LI10, LV3, ST36 for 20 minutes, respectively. Both groups had tactile stimulation in the order of the right LI1, LI10, LV3, ST36 before and after acupuncture for a block of 21 seconds repeated 3 times. The blood oxygen level dependent (BOLD) fMRI was used to observe the brain and somatosensory cortex signal activation. RESULTS We compared the signal activation before and after acupuncture needling, and the images showed signal activation after removing the acupuncture needles and the contralateral somatosensory association cortex, the postcentral gyrus, and the parietal lobe were more activated in the SA group. The right occipital lobe, the lingual gyrus, the visual association cortex, the right parahippocampal gyrus, the limbic lobe, the hippocampus, the left anterior lobe, the culmen, and the cerebellum were activated in the ULLA group. CONCLUSIONS We concluded that there were different signal activations of BOLD fMRI before and after SA versus ULLA, which can be thought to be caused by the sensitivity of acupoints and the different sensory receptors to acupuncture needling.

Can the Neutrophil-to-Lymphocyte Ratio Appropriately Predict Carotid Artery Stenosis in Patients with Ischemic Stroke?-A Retrospective Study.

BACKGROUND Carotid stenosis is a risk factor in ischemic stroke. Although C-reactive protein, interleukin-6, and tumor necrosis factor-alpha are known to predict carotid atherosclerosis, they are difficult to obtain in clinical practice. By studying the association between neutrophil-to-lymphocyte ratio (NLR) and carotid artery intima-media thickening (IMT) in patients with ischemic stroke, we determined that the NLR can predict carotid stenosis. METHODS We selected 252 patients with acute to subacute ischemic stroke who underwent carotid ultrasonography and complete and differential blood cell count tests. We collected data on sex, age, body mass index (BMI), alcohol consumption, smoking, hypertension, diabetes mellitus, dyslipidemia, and heart disease. Male and female patients were analyzed separately. We divided the subjects into 2 groups according to carotid IMT, and compared baseline characteristics and NLR between the 2 groups. The regression analysis was adjusted for confounding factors such as age, BMI, NLR, smoking, alcohol consumption, and a medical history of hypertension, diabetes mellitus, dyslipidemia, or heart disease. RESULTS Carotid IMT tended to significantly increase with NLR and age in men and with age in women. In men, multiple linear regression analyses adjusted for confounding factors showed that NLR (P < 0.001) and age (P = 0.001) had a significant positive association with carotid IMT (adjusted R(2) = 0.185, root mean squared error [MSE] = 0.152). However, no parameters showed significant positive associations in women. CONCLUSION NLR can be a clinically significant predictor of the degree of carotid stenosis in male patients with ischemic stroke. However, additional studies are required to obtain more concrete results.

Effects of GV20 Acupuncture on Cerebral Blood Flow Velocity of Middle Cerebral Artery and Anterior Cerebral Artery Territories, and CO2 Reactivity During Hypocapnia in Normal Subjects

OBJECTIVES Acupuncture has been gaining popularity among practitioners of modern medicine as an alternative and complementary treatment. However, the mechanism of its therapeutic effect still remains uncertain. The present study chose the GV20 acupoint to evaluate acupoint effectiveness, hypothesizing that its stimulation induces cerebrovascular responses. DESIGN AND SETTING The effects of GV20 acupuncture treatment on middle cerebral artery (MCA) and anterior cerebral artery (ACA) blood flow velocities, and CO(2) reactivity during hypocapnia were evaluated in 10 healthy male subjects (mean age 25.6 ± 0.8 years). Measurements were done at rest and during hypocapnia, and were repeated four times each at different cerebral artery territories with an interval of 1 week. MCA and ACA blood flow velocities were measured with a transcranial Doppler flowmeter. Blood flow velocity was corrected to 40 mm Hg of end-tidal CO(2) partial pressure (P(ETCO2)), and was expressed as CV40. CO(2) reactivity was measured as percent change in mean blood flow velocity/mm Hg P(ETCO2). RESULTS Mean MCA and ACA blood flow velocities at rest, CV40, and CO(2) reactivity during hypocapnia increased significantly after GV20 acupuncture treatment, whereas mean arterial blood pressure and pulse rate at rest did not change significantly. The increases in MCA and ACA blood flow velocity were associated with improved CO(2) reactivity after GV20 acupuncture treatment. CONCLUSIONS The data suggest that GV20 acupuncture treatment increases cerebral blood flow. The results of this small-scale study provide preliminary evidence for acupuncture effectiveness.

A comparison of brain activity between healthy subjects and stroke patients on fMRI by acupuncture stimulation

ObjectiveTo investigate brain activity patterns during acupuncture in stroke patients, and to compare the result with normal subjects using functional magnetic resonance imaging (fMRI).MethodsA total of 11 stroke patients with motor weakness and 10 healthy subjects were studied. fMRI was performed during acupuncture on the left side at points Quchi (LI11) and Zusanli (ST36). Data were analyzed using statistical parametric maps of brain activation induced by acupuncture stimulation.ResultsThe results showed that stimulation of both LI11 and ST36 produced significantly different brain activation patterns between the two groups. The normal group showed a greater overall activation than the stroke group. In the normal group, parts of the frontal lobe, parietal lobe, sub-lobar, cerebellum and midbrain regions were activated by acupuncture at the left LI11. On the other hand, only the right side of the inferior parietal lobule region was activated in the stroke patients. When the left ST36 was stimulated in the normal group, both sides of the frontal lobe, parietal lobe, temporal lobe, and sub-lobar, and the left side of occipital lobe, and the right side of cerebellum and midbrain regions were activated. For the same stimulation in the stroke group, only both sides of the inferior parietal lobule and cerebellum regions were activated (P<0.05, cluster level). Deactivation pattern was not noted during any acupuncture stimulation in both groups.ConclusionBrain signal activations during the same acupuncture were different between the healthy and the stroke patients, and the effects showed a correlation of different acupuncture points.

A Preliminary Study on the Inhibitory Effect of Chunghyul-dan on Stroke Recurrence in Patients with Small Vessel Disease

Abstract Objective: Chunghyul-dan is a combinatorial herbal medicine, and previous works reported that it had therapeutic effects for microangiopathy, which is a major part in the progression of small vessel disease, as having anti-hypertensive, anti-hyperlipidemic, anti-apoptotic, anti-oxidative and anti-inflammatory activities. Therefore, we examined the inhibitory effect of Chunghyul-dan on stroke recurrence in patients with small vessel disease. Methods: We prescribed Chunghyul-dan 600 mg a day to the patients with small vessel disease, and monitored stroke recurrence, drug compliances and adverse effect for 2 years. And then we performed follow-up brain MRI to find new vascular lesion after 2 years of Chunghyul-dan medication. As for the control, we recruited the subjects who had been managed with antiplatelet agents from a western medical hospital, and compared the rate of stroke recurrence. Results: There were 148 subjects who had been treated with Chunghyul-dan for 2 years, and new vascular events were found in three subjects. On the other hand, 208 subjects were managed with anti-platelet agents for 2 years in a Western medical hospital, and 17 of them had stroke recurrence. Therefore, 2 years of Chunghyul-dan medication reduced the odds ratio of stroke recurrence by 77% compared to the anti-platelet agents managed control. The inhibition rate increased to 79%, when adjusted for other relevant risk factors for stroke occurrence. During the study, no adverse effect was detected. Conclusion: We suggest that Chunghyul-dan could be useful for inhibition of stroke recurrence by preventing the progression of microangiopathy. Further study with a randomized controlled trial is needed to confirm this suggestion.