• Investigative Magnetic Resonance Imaging
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• v.21 no.2
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• pp.65-70
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• 2017

Purpose: To optimize the saturation time and maximizing the pH-weighted difference between the normal and ischemic brain regions, on 3-tesla amide proton transfer (APT) imaging using an in vivo rat model. Materials and Methods: Three male Wistar rats underwent middle cerebral artery occlusion, and were examined in a 3-tesla magnetic resonance imaging (MRI) scanner. APT imaging acquisition was performed with 3-dimensional turbo spin-echo imaging, using a 32-channel head coil and 2-channel parallel radiofrequency transmission. An off-resonance radiofrequency pulse was applied with a Sinc-Gauss pulse at a $B_{1,rms}$ amplitude of $1.2{\mu}T$ using a 2-channel parallel transmission. Saturation times of 3, 4, or 5 s were tested. The APT effect was quantified using the magnetization-transfer-ratio asymmetry at 3.5 ppm with respect to the water resonance (APT-weighted signal), and compared with the normal and ischemic regions. The result was then applied to an acute stroke patient to evaluate feasibility. Results: Visual detection of ischemic regions was achieved with the 3-, 4-, and 5-s protocols. Among the different saturation times at $1.2{\mu}T$ power, 4 s showed the maximum difference between the ischemic and normal regions (-0.95%, P = 0.029). The APTw signal difference for 3 and 5 s was -0.9% and -0.7%, respectively. The 4-s saturation time protocol also successfully depicted the pH-weighted differences in an acute stroke patient. Conclusion: For 3-tesla turbo spin-echo APT imaging, the maximal pH-weighted difference achieved when using the $1.2{\mu}T$ power, was with the 4 s saturation time. This protocol will be helpful to depict pH-weighted difference in stroke patients in clinical settings.

• Journal of Korean Neurosurgical Society
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• v.29 no.7
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• pp.853-860
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• 2000

Objective : The purpose of our experimental study was to analysis the advantages and disadvantages in the reversible and irreversible cerebral ischemic models with rats by staining with Neutral Red(NR) solusion, 2% 2,3,5-triphenyltetrazolium chloride(TTC) and Hematoxylin & Eosin(H & E). Methods : We have measured the range of cerebral infarction in the rat to get a suitable ischemic model along the object of study with and without craniectomy. With craniectomy, 9 rats were sacrificed for irreversible cerebral ischemic model by means of ligation at proximal(group I) and distal(group II), and coagulation at proximal(group III) middle cerebral artery. Also, 6 rats were sacrificed for irreversible(group IV) and reversible(group V) cerebral ischemic model using nylon thread without craniectomy. The sizes of infarction were measured by staining the coronal sections of the brain with NR solusion, TTC and H & E. Results : There are no difference of physiological parameters comparing the each group. Cerebral infarction was not observed in group II, but it's volume was largest in group IV. Disadvantages of craniectomy group(I, II, III) are the long duration of operation and cortical damage by procedure. It's advantage is confirmation of the middle cerebral artery occlusion and cessation of blood flow through the operative microscope. In case of ischemic models using nylon thread (group IV, V), it is hard to identify the interruption or recirculation of blood flow through the middle cerebral artery, but the advantage is the simplicity of operative technique which reduces the operation time and minimizes the cerebral damage due to craniectomy. Therefore, it seems important to set up the reversible and irreversible ischemic models by carefully considering advantages and disadvantages listed above. Conclusion : TTC staining seems to be effective since it reflects the histological damage sufficiently and quickly. It is hoped that researches focused on ischemic penumbra, which became popular recently, will be further carried on with use of NR staining, optical microscope and electron microscope.

• Analytical Science and Technology
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• v.28 no.6
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• pp.361-369
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• 2015

The precise mechanism underlying the therapeutic efficacy of an extraction powder of Angelica gigas (AGE) for the treatment of degenerative osteoarthritis was investigated in primary cultured rabbit chondrocytes and in a monosodium-iodoacetate (MIA)-induced osteoarthritis rat model. The treatment with AGE (50 μg/mL) effectively inhibited NF-B activation. The anti-inflammatory mechanism was clarified by gelatin zymography and western blotting measurements of matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9) activities. The AGE (50 μg/mL) treatment significantly reduced MMP-9 activity. The constituents of AGE— decursinol, decursin, and decursinol angelate—were determined by LC-MS/MS after a 24 hr treatment of rabbit chondrocytes. The contents of the major products, decursin and decursinol angelate, were 3.62±0.47 and 2.14 ±0.36 μg/mg protein, respectively in AGE-treated (50 μg/mL) rabbit chondrocytes. An in vivo animal study on rats fed a diet containing 25, 50, and 100 mg/kg AGE for 3 weeks revealed a significant inhibition of the MMPs in the MIA-induced rat articular cartilage. The genetic expression of arthritic factors in the articular cartilage was examined by RT-PCR of collagen Type I, collagen Type II, aggrecan, and MMP (MMP3, MMP-9, MMP13). Specifically, AGE up-regulated the expression of collagen Type I, collagen Type II, and aggrecan and inhibited MMP levels at all tested concentrations. Collectively, AGE showed a strong specific site of action on MMP regulation and protected against the degeneration of articular cartilage via cellular regulation of MMP expression both in vitro and in vivo.

• Journal of Physiology & Pathology in Korean Medicine
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• v.21 no.5
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• pp.1194-1199
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• 2007

Osteoarthritis(OA) is a degenerative joint disease characterized by fibrillation and erosion in cartilage tissue, chondrocyte proliferation and osteophyte formation at the joint margins, and sclerotis of subchondral bone. We investigated the effects of Acyranthes Radix administration and Cervi Cornu Parvum aqua-acupuncture in monosodium iodoacetate(MIA) induced experimental osteoarthritis model. Sprague-Dawley 60 rats of 7-8 weeks, weight $240{\pm}10\;g$ were divided into two groups including the sham operation group(15 rats) and ostoarthritis group(45 rats). Histopathological examination, Mankin's score, and the measurement of inflammation factor were performed. Histological findings that are similar to those observed in human osteoarthritis, such as disorganization of chondrocytes, erosion and fibrillation of cartilage surface, and subchondral bone exposure were observed in a MIA-induced osteoarthritis model. Saflanin-O fast green staining revealed that marked diffuse reduction of proteoglycans treated with MIA. The Mankin's score were closely correlated to the grade of histological findings. The level of prostaglandin E2 and C-reactive protein were decreased experimental groups. We conclude that Acyranthes Radix administration and Cervi Cornu Parvum aqua-acupuncture, and combination treatment exerts a beneficial influence on the cartilage lesion in osteoarthritis rat.

• Journal of Veterinary Science
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• v.21 no.1
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• pp.6.1-6.12
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• 2020

Currently, the optimal resuscitation fluid remains debatable. Therefore, in the present study, we designed a trometamol-balanced solution (TBS) for use as a resuscitation fluid for hemorrhagic shock. Hemorrhagic shock was induced in 18 male Wistar-Kyoto rats, which were assigned to normal saline (NS), Ringer's solution (RS), and TBS groups. During the hemorrhagic state, their hemodynamic parameters were recorded using an Abbott i-STAT analyzer with the CG4+ cartridge (for pH, pressure of carbon dioxide, pressure of oxygen, total carbon dioxide, bicarbonate, base excess, oxygen saturation, and lactate), the CG6+ cartridge (for sodium, potassium, chloride, blood glucose, blood urea nitrogen, hematocrit, and hemoglobin), and enzyme-linked immunosorbent assay kits (calcium, magnesium, creatinine, aspartate aminotransferase, alanine aminotransferase, bilirubin, and albumin). Similar trends were found for the parameters of biochemistries, electrolytes, and blood gas, and they revealed no significant changes after blood withdrawal-induced hemorrhagic shock. However, the TBS group showed more effective ability to correct metabolic acidosis than the NS and RS groups. TBS was a feasible and safe resuscitation solution in this study and may be an alternative to NS and RS for resuscitation in hemorrhagic shock patients without liver damage.

• The Korean Journal of Food And Nutrition
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• v.33 no.6
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• pp.614-623
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• 2020

The objective of this study was to produce a nutrient delivery system (NDS) using sialic acid extracted from edible bird's nest (EBN), which improves brain function in patients with Alzheimer's disease and Parkinson's disease, by affinity bead technology (ABT). The inhibitory activity of acetylcholinesterase (AChE) and pyramidal cells in the dentate gyrus of the hippocampus were analyzed to investigate the effect of a sialic acid NDS on Alzheimer's disease. Also, the effect of a sialic acid NDS on Parkinson's disease was evaluated by rota-rod test and pole test in an animal model. Among the groups treated with donepezil, EBN, and sialic acid NDS, the AChE activity was the lowest in the sialic acid NDS-treated group. The results of the hippocampus analysis of the rat model confirmed that the sialic acid NDS inhibited amyloid-beta accumulation depending upon the concentration. Also, the sialic acid NDS group showed more improvement in motor deterioration than the1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced group in both the rota-rod test and pole test. Therefore, the sialic acid NDS had an effect of protecting not only Alzheimer's disease by inhibiting AChE and amyloid-beta accumulation, but Parkinson's disease by preventing neurotoxicity induced by MPTP.

• Journal of Biomedical Engineering Research
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• v.33 no.3
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• pp.148-154
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• 2012

Hemorrhagic shock is a primary cause of deaths resulting from injury in the world. Although many studies have tried to diagnose accurately hemorrhagic shock in the early stage, such attempts were not successful due to compensatory mechanisms of humans. The objective of this study was to construct a survival prediction model of rats in acute hemorrhagic shock using a random forest (RF) model. Heart rate (HR), mean arterial pressure (MAP), respiration rate (RR), lactate concentration (LC), and peripheral perfusion (PP) measured in rats were used as input variables for the RF model and its performance was compared with that of a logistic regression (LR) model. Before constructing the models, we performed 5-fold cross validation for RF variable selection, and forward stepwise variable selection for the LR model to examine which variables were important for the models. For the LR model, sensitivity, specificity, accuracy, and area under the receiver operating characteristic curve (ROC-AUC) were 0.83, 0.95, 0.88, and 0.96, respectively. For the RF models, sensitivity, specificity, accuracy, and AUC were 0.97, 0.95, 0.96, and 0.99, respectively. In conclusion, the RF model was superior to the LR model for survival prediction in the rat model.

• Journal of the Korean Society of Physical Medicine
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• v.8 no.1
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• pp.79-89
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• 2013

PURPOSE: To identify the effects of single trial transcutaneous electrical nerve stimulation (TENS) application on chronic neuropathic pain and the repeated TENS application to development of neuropathic pain following peripheral nerve injury. METHODS: First, 20 rats were given the median nerve ligation to induce chronic neuropathic pain. After the ligation, neuropathic pain was assessed by measuring the forepaws withdrawal threshold to von Frey filaments for 3 weeks. Afterward, rats were randomly divided into TENS group and placebo-TENS group. TENS (frequency 100Hz, pulse width $200{\mu}s$) was applied to the forearm for 20 minutes. Second, 34 rats were randomly allocated into two group after median nerve ligation: TENS group and placebo-TENS group. Both interventions were applied to the forearm for 20 minutes from 1 day to 3 weeks after injury. Neuropathic pain to mechanical was measured on each rat for 3 weeks. RESULTS: Exeprimental rats showed a clear neuropathic pain-like behaviors, such as reduced forepaw withdrawal threshold to mechanical stimulation for 3 weeks, after median nerve ligation. And, TENS decreased effectively the chronic neuropathic pain originated from median nerve injury. TENS also diminished the development of neuropathic pain after nerve injury. CONCLUSION: Our animal model studying for neuropathic pain following median nerve injury may be useful to investigate peripheral neuropathic pain in human. Also, TENS may be used to mediate chronic neuropathic pain and to prevent the development of neuropathic pain following median nerve injury.

• BMB Reports
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• v.47 no.12
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• pp.679-684
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• 2014

GM-CSF plays a role in the nervous system, particularly in cases of injury. A therapeutic effect of GM-CSF has been reported in rat models of various central nervous system injuries. We previously showed that GM-CSF could enhance long-term recovery in a rat spinal cord injury model, inhibiting glial scar formation and increasing the integrity of axonal structure. Here, we investigated molecular the mechanism(s) by which GM-CSF suppressed glial scar formation in an in vitro system using primary astrocytes treated with TGF-${\beta}$. GM-CSF repressed the expression of chondroitin sulfate proteoglycan (CSPG) core proteins in astrocytes treated with TGF-${\beta}$. GM-CSF also inhibited the TGF-${\beta}$-induced Rho-ROCK pathway, which is important in CSPG expression. Finally, the inhibitory effect of GM-CSF was blocked by a JAK inhibitor. These results may provide the basis for GM-CSF's effects in glial scar inhibition and ultimately for its therapeutic effect on neural cell injuries.

• Archives of Pharmacal Research
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• v.24 no.6
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• pp.572-577
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• 2001

The feasibility of skin penetration was studied for aspalatone (AM, acetylsalicylic acid maltol ester), a novel antithrombotic agent. In this studys hairless mouse dorsal skins were used as a model to select composition of vehicle and AM. Based on measurements of solubility and partition coefficient, the concentration of PC that showed the highest flux for AM across the hairless mouse skin was found to be 40%. The cumulative amount permeated at 48 h, however, appear inadequate, even when the PC concentration was employed. To identify a suitable absorption enhancer and its optimal concentration for AM, a number of absorption enhancers and a variety of concentration were screened for the increase in transdermal flux of AM. Amongst these, linoleic acid (LOA) at the concentration of 5% was found to have the largest enhancement factor (i.e., 132). However, a further increase in AM flux was not found in the fatty acid concentration greater than 5%, indicating the enhancement effect is in a bell-shaped currie. In a study of the effect of AM concentration on the permeation, there was no difference in the permeation rate between 0.5 and 1% for AM, below its saturated concentration. At the donor concentration of 2%, over the saturated condition, the flux of AM was markedly increased. A considerable degradation of AM was found during permeation studies, and the extent was correlated with protein concentrations in the epidermal and serosal extracts, and skin homogenates. In rat dorsal skins, the protein concentration decreased in the rank order of skin homogenate > serosal extract > epidermal extract. Estimated first order degradation rate constants were $6.15{\pm}0.14,{\;}0.57{\pm}0.02{\;}and{\;}0.011{\pm}{\;}0.004{\;}h^{-1}$ for skin homogenate, serosal extract and epidermal extract, respectively. Therefore, it appeared that AM was hydrolyzed to some extent into salicylmaltol by esterases in the dermal and subcutaneous tissues of skin. taken together, our data indicated that transdermal delivery of AM is feasible when the combination of PC and LOA is used as a vehicle. However, since AM is not metabolically stable, acceptable degradation inhibitors may be nervessary to fully realize the transdermal delivery of the drug.