• Journal of The Korean Society of Emergency Medicine
• /
• v.28 no.5
• /
• pp.457-466
• /
• 2017

Purpose: Traumatic brain injury (TBI) is a significant cause of morbidity and mortality worldwide. Severity of the initial insult is one of the most significant factors affecting outcome following TBI. In order to investigate the mechanisms of cellular injury and develop novel therapeutic strategies for TBI, we designed a standardized animal TBI model and evaluated histological and functional outcomes according to the degree of impact severity. Methods: Male adult C57Bl/6 mice underwent controlled cortical impact (CCI) at varying depths of deflection (1.0-2.0 mm). We performed hematoxylin and eosin staining at 7 days after recovery from TBI. Neurobehavioral characterization after TBI was analyzed by the Barnes maze test, passive avoidance test, open field test, rotarod test, tail suspension test, and light/dark test. Results: We observed a graded injury response according to the degree of deflection depths tested (diameter, 3 mm; velocity, 3 m/s; and duration, 500 ms) compared to sham controls. In the Barnes maze test, the severe TBI (2 mm depth) group showed reduced spatial memory as compared with the sham and mild TBI (1 mm depth) groups at 7 days after TBI. There was a significant difference in the results of the open field test and light/dark test among the three groups. Conclusion: Our findings demonstrate that the graded injury responses following TBI resulted in differential histopathological and behavioral outcomes in a mouse experimental CCI model. Thus, a model of CCI with histologic/behavioral outcome analysis may offer a reliable and convenient design for preclinical TBI research involving mice.

• Journal of the Korean Society of Food Science and Nutrition
• /
• v.43 no.6
• /
• pp.799-806
• /
• 2014

The present study was conducted to evaluate the effects of extract from Eriobotrya japonica leaves (EJE) on cognitive impairment induced by scopolamine, a muscarinic antagonist, in rats. Scopolamine injection (1 mg/kg, i.p.) impaired performance in rats in the passive avoidance test as well as in water maze test and severely reduced cholinergic system reactivity, as indicated by reduced acetylcholine levels and increased acetylcholinesterase activity. Daily administration of EJE significantly increased step-through latency in the passive avoidance test, reduced escape latency, and increased time spent in the platform quadrant in the Morris water maze test. EJE protected against scopolamine-induced cholinergic system deficit, including reduced acetylcholine levels and increased acetylcholinesterase activity in whole brain homogenates. These results suggest that EJE provides a significant anti-amnesic effect against scopolamine-induced cholinergic system deficits and cognitive impairment.

• Biomolecules & Therapeutics
• /
• v.12 no.4
• /
• pp.242-249
• /
• 2004

The main aim of this study was to investigate stress related activities of Sun-ginseng extract as a candidate for anti-stress-related functional supplement by comparing its effect to those of red ginseng, which is also known to alleviate stress. Normal group was not exposed to stress while the control group was exposed to stress. Rats were orally administered once a day with 200 mg red ginseng (RG) extract, 100 or 200 mg Sun-ginseng (SG) extract/kg body weight. Mice were given water containing 400 mg red ginseng extract, 200 or 400 mg SG/100 mL potable water. Rats were given supplements for 5 days without stress, and 5 days with restraint and electroshock stress. After final stress, stress-related behavioral changes of experimental animals were recorded and levels of blood corticosterone were measured. Mice were given supplements for 5 days through drinking water, and then fatigue related motor activity were recorded. SG-supplementation partially blocked stress effect on locomotion and elevated plus maze test in rats, and also partially blocked stress-induced behavioral changes such as freezing, burrowing, smelling, facewashing, grooming and rearing behavior in rats. SG-supplementation decreased blood corticosterone level which is increased by stress in rats. Effects of SG may not be modulated by GABAnergic nervous system. SG-supplementation prolonged swimming time and staying time on the wire and rotarod wheel in mice. These results suggest that SG partially protects living organisms from stress attack in some cases and thus has the potential to be used as a functional food to alleviate stress response.

• Journal of Korean Neurosurgical Society
• /
• v.39 no.2
• /
• pp.130-135
• /
• 2006

Objective : After ischemic stroke, partial recovery of function frequently occurs and may depend on the plasticity of axonal connections. Here, we examine whether blockade of the Nogo/NogoReceptor[NgR] pathway might enhance axonal sprouting and thereby recovery after focal brain infarction. Methods : Adult male Sprague Dawley rats weighing $250{\sim}350g$ were used. Left middle cerebral artery occlusion[MCAO] was induced with a intraluminal filament. An osmotic mini pump [Alzet 2ML4, Alza Scientific Products, Palo Alto, CA] for the infusion of NgR-Ecto[310]-Fc to block Nogo/NgR pathway was implanted 1 week after cerebral ischemia. Prior to induction of ischemia, all animals received training in the staircase and rotarod test. Two weeks after biotin dextran amine injection, animals were perfused transcardially with PBS, followed by 4% paraformadehyde/PBS solution. Brain and cervical spinal cord were dissected. Eight coronal sections spaced at 1mm intervals throughout the forebrain of each animal with cresyl violet acetate for determination of infarction size. Images of each section were digitized and the infarct area per section was measured with image analysis software. Results : Histological examination at 11 weeks post-MCAO demonstrates reproducible stroke lesions and no significant difference in the size of the stroke between the NgR[310]Ecto-Fc protein treated group and the control group. Behavioral recovery is significantly better and more rapid in the NgR-Ecto[310]-Fe treated group. Blockade of NgR enhances axonal sprouting from the uninjured cerebral cortex and improves the return of motor task performance. Conclusion : Pharmacological interruption of NgR allows a greater degree of axonal plasticity in response this is associated with improved functional recovery of complicated motor tasks.

• Biomolecules & Therapeutics
• /
• v.14 no.2
• /
• pp.83-89
• /
• 2006

The main aim of this study was to characterize the pharmacological profile of flavonoids utilizing behavioral tests and to investigate how the psychopharmacological activities of wogonin, baicalein and oroxylin A are different. Wogonin, baicalein and oroxylin A were intraperitoneally injected as dosages of 2.5, 5, 10 and 20 mg/kg. In the locomotor activity, Rota-rod test, and elevated plus-maze tests, the behavioral parameters were analyzed by automatic systems. Thiopental induced sleeping time was measured. Water extract of S. baicalensis didn't exhibit sedative effect. Wogonin and bacalein exhibited anxiolytic activity although it was less potent than buspirone. Wogonin and baicalein decreased locomotor activity at a dose of 10 mg/kg. Wogonin also shortened significantly running time on the rota-rod at doses of 5 and 10 mg/kg. Wogonin and baicalein enhanced sleeping at doses of 5 and 10 mg/kg. These results indicate that wogonin produce anxiolysis with sedation and so did bacalein with mild sedation. On the contrary, oroxylin A enhanced running activity on the rotarod and did't depress locomotor activity. Oroxylin A significantly hindered sleeping rather than helped it at doses of 5 and 10 mg/kg. Oroxylin A didn't produce anxiolysis and instead, produce awakening effect. This study demonstrates that wogonin and bacalein exhibited anxiolytic activity with mild sedation, but oroxylin A didn't produce anxiolysis and instead, produce awakening effect. This result indicates that anxiolytic effect without sedation induced by Scutellaria baicalensis is produced by combination of flavonoids.

• Annals of Clinical Neurophysiology
• /
• v.15 no.2
• /
• pp.53-58
• /
• 2013

Background: The autophagy is the major route for lysosomal degradation of misfolded protein aggregates and oxidative cell components. We hypothesized that rapamycin (autophagy enhancer) would prolong the survival of motor neuron and suppress the disease progression in amyotrophic lateral sclerosis (ALS). Methods: A total of 24 transgenic mice harboring the human G93A mutated SOD1 gene were used. The clinical status involving rotarod test and survival, and biochemical study of ALS mice model were evaluated. Results: The onset of symptoms was significantly delayed in the rapamycin administration group compared with the control group. However, after the clinical symptom developed, the rapamycin exacerbated the disease progression and shortened the survival of ALS mice model, and apoptosis signals were up-regulated compared with control group. Conclusions: Even though further detailed studies on the relevancy between autophagy and ALS will be needed, our results revealed that the rapamycin administration was not effective for being novel promising therapeutic strategy in ALS transgenic mice and exacerbated the apoptosis.

• Annals of Clinical Neurophysiology
• /
• v.7 no.2
• /
• pp.101-106
• /
• 2005

Background: There is no currently effective treatment for amyotrophic lateral sclerosis (ALS), although this disorder is a progressive neurodegenerative disease resulting in death within several years. Because recent evidence suggests that homocysteine (HC) is highly related to neurodegenerative disorders with aging, we tried to elucidate the effects of multi-vitamin therapy on G93A SOD1 transgenic mice. Methods: We treated this murine model of ALS with multi-vitamin (folic acid 1.97 mg/day, pyridoxine 0.98 mg/day, cyanocobalamin 0.1 mg/day) from 45 days of age, per oral. We performed the rotarod test from postnatal $10^{th}$ week, weekly. Results: We found that multi-vitamin reinforcement significantly prolonged average lifespan and delayed disease onset with improvement of motor performance. However, it did not significantly slow disease progression and statistical differences of weight loss were not observed between in transgenic mice and controls. Conclusions: These results suggest that multi-vitamin can be a potent therapeutic strategy for familial forms of ALS.

• Biomolecules & Therapeutics
• /
• v.27 no.2
• /
• pp.178-184
• /
• 2019

Parkinson's disease is a neurodegenerative disease characterized by the progressive loss of dopaminergic neurons within the substantia nigra pars compacta. In the present study, we investigated whether ${\beta}-Lapachone$ (${\beta}-LAP$), a natural naphthoquinone compound isolated from the lapacho tree (Tabebuia avellanedae), elicits neuroprotective effects in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced Parkinson's disease mouse model. ${\beta}-LAP$ reduced the tyrosine hydroxylase (TH)-immunoreactive fiber loss induced by MPTP in the dorsolateral striatum, and alleviated motor dysfunction as determined by the rotarod test. In addition, ${\beta}-LAP$ protected against MPTP-induced loss of TH positive neurons, and upregulated B-cell lymphoma 2 protein (Bcl-2) expression in the substantia nigra. Based on previous reports on the neuroprotective role of nuclear factor-E2-related factor-2 (Nrf2) in neurodegenerative diseases, we investigated whether ${\beta}-LAP$ induces upregulation of the Nrf2-hemeoxygenae-1 (HO-1) signaling pathway molecules in MPTP-injected mouse brains. Western blot and immunohistochemical analyses indicated that ${\beta}-LAP$ increased HO-1 expression in glial fibrillary acidic protein-positive astrocytes. Moreover, ${\beta}-LAP$ increased the nuclear translocation and DNA binding activity of Nrf2, and the phosphorylation of upstream adenosine monophosphate-activated protein kinase (AMPK). ${\beta}-LAP$ also increased the localization of p-AMPK and Nrf2 in astrocytes. Collectively, our data suggest that ${\beta}-LAP$ exerts neuroprotective effect in MPTP-injected mice by upregulating the p-AMPK/Nrf2/HO-1 signaling pathways in astrocytes.

• The Korea Journal of Herbology
• /
• v.21 no.2
• /
• pp.151-158
• /
• 2006

Objectives : The purpose of the present study is to observe the neuroprotective effect of the $NeuBo153^{\circledR}$ on transient focal cerebral ischemia in rats. Methods : $NeuBo153^{\circledR}$ was made by mixing the herbs, mainly the root of Panax ginseng, the root of Rehmannia glutinosa and Poria cocos, the stem bark of Acanthopanax senticosus, the root of Scutellaria baicalensis and Mel, and heating for 96 hours. Transient Focal cerebral ischemia (2 h of ischemia, 22 h of reperfusion) was induced by intraluminal suture method with SD rats. Sensory motor function was tested by rotarod test, prehensile traction test, beam balance test and foot fault test at 24 h after ischemia. The brain slices were stained by 2% 2, 3, 5-triphenyltetrazolium chloride and the infarct volume was measured by graphic analyzer at 24 h after ischemia. Results : $NeuBo153^{\circledR}$ treated group did not show significant differences compared with vehicle treated group in body temperature. Oral administration of $NeuBo153^{\circledR}$ reduced brain infarct volume by 29.7% compared with vehicle treated group. $NeuBo153^{\circledR}$ also showed protective effects on sensory motor functional deficits. Conclusion : $NeuBo153^{\circledR}$ treatment reduced brain damage and improved functional deficits induced by MCAo. It showed neuroprotective effects even when treatment was relayed 2 h after injury. Further research is required to evaluating long term functional recovery am accurate therapeutic range and mechanisms.

• Toxicological Research
• /
• v.23 no.1
• /
• pp.11-17
• /
• 2007

This study was carried out to investigate the effect of LAB (Lactic acid bacteria: Lactobacillus acidophilus, Bifidobacterium bifidum and Streptococcus thermophilus) on detoxication of damaged liver in carbon tetrachloride ($CCl_4$) and ethanol (25%)-treated rats. Rats had been daily (twice a day) pre-treated with saline (0.5 ml/kg: untreated group), $CCl_4$ (0.5 ml/kg: other groups) for 6 days. At seventh day, after treating rat with $CCl_4$ and then, mixture of LAB ($10^{11}$/0.5 ml: LAB group), saline (0.5 ml/kg: untreated group, $CCl_4$ group), and biphenyl dimethyl dicarboxylate (DDB) (50 mg/kg: DDB group) were treated orally with $CCl_4$ for 8 days. Ethanol is treated as the same manner instead of $CCl_4$. To investigate the hepatoprotective effect, rats treated with $CCl_4$ and ethanol were analyzed with serum GOT and GPT level. The GOT and GPT levels of LAB group was lower than the level of $CCl_4$ and DDB group. Especially, compared with data of $CCl_4$ group, GPT activity showed statistically significant result in the significance level of p < 0.05. The LAB group treated with ethanol also showed lower level of GOT and GPT than the other control groups treated with ethanol. The triglyceride level of serum decreased more in a group treated special materials (DDB and LAB group) than ethanol group. As well, the effect of LAB on the antifatigue has been investigated. The animals (10/group) were divided into 4 groups (untreated group, Carrier group, Red-ginseng group, LAB group). Each group was given carrier (0.9 mg/0.2 ml), red ginseng extract (200 mg/kg), and mixture of LAB ($10^{11}$/0.2 ml). Special materials were given for three weeks. After finishing treating through oral, horizontal wire test, rotarod test, and forced swimming test were performed. The time of resistance to fatigue of the group, fed with mixture of LAB, was longer than the time when mice treated with red-ginseng that the effect was already revealed. The result of this study revealed that LAB could decrease hepatocelluar injury compared with rats treated orally with $CCl_4$ and ethanol, and could also decrease fatigue.