[Show abstract][Hide abstract] ABSTRACT: Ulinastatin is a urinary trypsin inhibitor, originally extracted and purified from human urine. Ulinastatin has cytoprotective effects against ischemic injury in several organs. In the present study, the neuroprotective effects of ulinastatin following ischemic cerebral injury in the hippocampus of gerbils was investigated. To induce transient global ischemia in gerbils, the common carotid arteries were occluded using aneurysm clips for 5 min, and the clips were then removed. Ulinastatin was subcutaneously injected into the gerbils once a day for 7 days at doses of 50,000 or 100,000 U/kg. The gerbils were confronted with a step‑down avoidance task, following which tissue samples from the gerbils were examined using terminal deoxynucleotidyl transferase‑mediated dUTP nick end labeling (TUNEL) staining, western blot analysis for B‑cell lymphoma (Bcl‑2) and Bcl‑2‑associated X protein (Bax), immunohistochemistry for caspase‑3 and immunofluorescence for 5‑bromo‑2'‑deoxyuridine. The numbers of TUNEL‑positive and caspase‑3‑positive cells in the hippocampal CA1 region increased following cerebral ischemia. The expression of Bax in the hippocampus increased, while the expression of Bcl‑2 in the hippocampus decreased following cerebral ischemia. These results confirmed that apoptosis in the hippocampus was enhanced following cerebral ischemia in gerbils. The levels of cell proliferation in the hippocampal dentate gyrus were also enhanced by ischemia, which is possibly an adaptive mechanism to compensate for excessive levels of apoptosis. Ulinastatin treatment inhibited ischemia‑induced apoptosis by suppressing apoptosis‑associated molecules, and thus ameliorated ischemia‑induced short‑term memory impairment. The cell proliferation in the hippocampus was also suppressed following ulinastatin treatment. These results suggested the use of ulinastatin as a therapeutic agent for patients with cerebral stroke.
Preview · Article · Apr 2015 · Molecular Medicine Reports
[Show abstract][Hide abstract] ABSTRACT: Exercise-induced muscle damage (EIMD), which is commonly associated with eccentric exercise, unaccustomed exercise, and resistance training, may lead to delayed-onset muscle soreness, swelling, decreased muscle strength, and range of motion. Many researchers have evaluated various interventions to treat the signs and symptoms of EIMD. However, the effects of massage after EIMD are unclear. Here, we investigated the effect of massage on muscle strength and proprioception following EIMD. All subjects randomly were divided into a EIMD-treated control group (n = 10) and an massage-treated after EIMD experimental group (n = 11). EIMD was induced by repeated exercise. Massage treatment was provided by physiotherapist for a 15 min. It consists of light stroking, milking, friction, and skin rolling. Lactate was evaluated by lactate pro analyzer in pre and post exercise. Surface electromyography (muscle activity) and sonography (muscle thickness) were used to confirm the muscular characteristics. Proprioception was investigated by dual inclinometer. As a result, massage treatment on the gastrocnemius after EIMD increased activation of the medial gastrocnemius during contraction (p < 0.05). In the lateral and medial gastrocnemius, the θs which is angle between muscle fibers and superficial aponeurosis showed a significant change (p < 0.05). However, there are no differences in the θd which is angle between muscle fibers and deep aponeurosis. We also found that proprioceptive acuity in the ankle joint was significantly greater in the massage-treated experimental group compared to that in the control group (p < 0.05). These findings suggest that massage of the gastrocnemius after EIMD can improve muscle strength and proprioception by influencing the superficial layer of the gastrocnemius.
No preview · Article · Sep 2014 · The Journal of Strength and Conditioning Research
[Show abstract][Hide abstract] ABSTRACT: During pregnancy, diabetes mellitus exerts detrimental effects on the development of the fetus, especially the central nervous system. In the current study, we evaluated the effects of postnatal treadmill exercise on short-term memory in relation with cell proliferation and apoptosis in the hippocampus of rat pups born to streptozotocin (STZ)-induced diabetic maternal rats. Adult female rats were mated with male rats for 24 h. Two weeks after mating, the pregnant female rats were divided into two groups: control group and STZ injection group. The pregnant rats in the STZ injection group were administered 40 mg/kg of STZ intraperitoneally. After birth, the rat pups were divided into the following four groups: control group, control with postnatal exercise group, maternal STZ-injection group, and maternal STZ-injection with postnatal exercise group. The rat pups in the postnatal exercise groups were made to run on a treadmill for 30 min once a day, 5 times per week for 2 weeks beginning 4 weeks after birth. The rat pups born to diabetic rats were shown to have short-term memory impairment with suppressed cell proliferation and increased apoptosis in the hippocampal dentate gyrus. Postnatal treadmill exercise alleviated short-term memory impairment by increased cell proliferation and suppressed apoptosis in the rat pups born to diabetic rats. These findings indicate that postnatal treadmill exercise may be used as a valuable strategy to ameliorate neurodevelopmental problems in children born to diabetics.
[Show abstract][Hide abstract] ABSTRACT: Prenatal environmental conditions affect the development of the fetus. In the present study, we investigated the effects of exposure to music and noise during pregnancy on neurogenesis and thickness in the motor and somatosensory cortex of rat pups.
The pregnant rats in the music-applied group were exposed to 65 dB of comfortable music for 1 hour, once per day, from the 15th day of pregnancy until delivery. The pregnant rats in the noise-applied group were exposed to 95 dB of sound from a supersonic sound machine for 1 hour, once per day, from the 15th day of pregnancy until delivery. After birth, the offspring were left undisturbed together with their mother. The rat pups were sacrificed at 21 days after birth.
Exposure to music during pregnancy increased neurogenesis in the motor and somatosensory cortex of rat pups. In contrast, rat pups exposed to noise during pregnancy showed decreased neurogenesis and thickness in the motor and somatosensory cortex.
Our study suggests that music and noise during the developmental period are important factors influencing brain development and urogenital disorders.
Full-text · Article · Sep 2013 · International neurourology journal
[Show abstract][Hide abstract] ABSTRACT: We investigated whether a hippotherapy simulator has influence on symmetric body weight bearing during gait in patients with stroke.
Stroke patients were divided into a control group (n = 10) that received conventional rehabilitation for 60 min/day, 5 times/week for 4 weeks and an experimental group (n = 10) that used a hippotherapy simulator for 15 min/day, 5 times/week for 4 weeks after conventional rehabilitation for 45 min/day. Temporospatial gait assessed using OptoGait and trunk muscles (abdominis and erector spinae on affected side) activity evaluated using surface electromyography during sit-to-stand and gait. Prior to starting the experiment, pre-testing was performed. At the end of the 4-week intervention, we performed post-testing.
Activation of the erector spinae in the experimental group was significantly increased compared to that in the control group (p < 0.01), whereas activation of the rectus abdominis decreased during sit-to-stand. Of the gait parameters, load response, single support, total double support, and pre-swing showed significant changes in the experimental group with a hippotherapy simulator compared to control group (p < 0.05). Moreover, activation of the erector spinae and rectus abdominis in gait correlate with changes of gait parameters including load response, single support, total double support, and pre-swing in experimental group.
These findings suggest that use of a hippotherapy simulator to patients with stroke can improve asymmetric weight bearing by influencing trunk muscles.
No preview · Article · Aug 2013 · Neurorehabilitation
[Show abstract][Hide abstract] ABSTRACT: Apoptotic neuronal cell death in the retina is a hallmark of diabetic retinopathy. Exercise has been recommended for the alleviation of symptoms in patients with diabetes. In the present study, the effect of treadmill exercise on apoptosis in the retinas of diabetic rats was investigated. Diabetes was induced by intraperitoneal injection of streptozotocin. The rats in the exercise groups ran on a treadmill for 30 min/day, 5 times a week, over the course of 6 weeks. In this study, the terminal deoxynucleotidyl transferase‑mediated dUTP nick‑end labeling (TUNEL) assay, immunohistochemistry staining of caspase‑3 and western blot analysis for Bax, Bcl‑2 and phosphorylated protein kinase B (p‑Akt) in the retinas of diabetic rats were performed. The results demonstrated that the number of TUNEL‑ and caspase‑3‑positive cells was increased in the retinas of diabetic rats, whereas treadmill exercise decreased these numbers. In addition, the expression of the pro‑apoptotic protein Bax and the anti‑apoptotic protein Bcl‑2 was enhanced in the retinas of diabetic rats. Treadmill exercise suppressed Bax and enhanced Bcl‑2 levels. The expression of the cell survival factor, p‑Akt, was decreased in the retinas of diabetic rats and treadmill exercise increased the expression of p‑Akt. The results of the present study demonstrated that treadmill exercise ameliorated diabetes‑induced apoptosis in retinal cells by enhancing p‑Akt levels in the retina. Treadmill exercise represents an effective strategy to delay or prevent the onset of ocular complications in diabetic patients.
Preview · Article · Apr 2013 · Molecular Medicine Reports
[Show abstract][Hide abstract] ABSTRACT: Ulinastatin is an intrinsic serine-protease urinary trypsin inhibitor that can be extracted and purified from human urine. Urinary trypsin inhibitors are widely used to treat patients with acute inflammatory disorders, such as shock and pancreatitis. However, although the anti-inflammatory activities of urinary trypsin inhibitors have been investigated, the mechanisms underlying their actions are not yet fully understood. In the present study, we evaluated the effect of ulinastatin on lipopolysaccharide (LPS)-induced inflammation in relation with nuclear factor-κB (NF-κB) activation using BV2 mouse microglial cells. To accomplish this, we performed a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, reverse transcription-polymerase chain reaction (RT-PCR), western blot analysis, electrophoretic mobility gel shift assay (EMSA), prostaglandin E2 (PGE2) immunoassay and nitric oxide (NO) detection. The results demonstrated that ulinastatin suppressed PGE2 synthesis and NO production by inhibiting the LPS-induced mRNA and protein expression of cyclooxygenase-2 (COX-2) and inducible NO synthase (iNOS) in BV2 mouse microglial cells. Ulinastatin suppressed the activation of NF-κB in the nucleus. These findings demonstrate that ulinastatin exerts analgesic and anti-inflammatory effects that possibly occur via the suppression of COX-2 and iNOS expression through the downregulation of NF-κB activity.
No preview · Article · Mar 2013 · International Journal of Molecular Medicine
[Show abstract][Hide abstract] ABSTRACT: Transient anterograde amnesia is occasionally observed in a number of conditions, including migraine, focal ischemia, venous flow abnormalities, and after general anesthesia. The inhalation anesthetic, isoflurane, is known to induce transient anterograde amnesia. We examined the involvement of brain-derived neurotrophic factor (BDNF) and its receptor tyrosine kinase B (TrkB) in the underlying mechanisms of the isoflurane-induced transient anterograde amnesia.
Adult male Sprague-Dawley rats were divided into three groups : the control group, the 10 minutes after recovery from isoflurane anesthesia group, and the 2 hours after recovery from isoflurane anesthesia group (n=8 in each group). The rats in the isoflurane-exposed groups were anesthetized with 1.2% isoflurane in 75% nitrous oxide and 25% oxygen for 2 hours in a Plexiglas anesthetizing chamber. Short-term memory was determined using the step-down avoidance task. BDNF and TrkB expressions in the hippocampus were evaluated by immunofluorescence staining and western blot analysis.
Latency in the step-down avoidance task was decreased 10 minutes after recovery from isoflurane anesthesia, whereas it recovered to the control level 2 hours after isoflurane anesthesia. The expressions of BDNF and TrkB in the hippocampus were decreased immediately after isoflurane anesthesia but were increased 2 hours after isoflurane anesthesia.
In this study, isoflurane anesthesia induced transient anterograde amnesia, and the expressions of BDNF and TrkB in the hippocampus might be involved in the underlying mechanisms of this transient anterograde amnesia.
Preview · Article · Mar 2013 · Journal of Korean Neurosurgical Society
[Show abstract][Hide abstract] ABSTRACT: Post‑traumatic stress disorder (PTSD) is an anxiety disorder triggered by life‑threatening events that cause intense fear. Exercise is known to have protective effects on neuropsychiatric diseases. The present study investigated whether treadmill exercise during pregnancy reduced or alleviated symptoms of PTSD in maternal rats. To induce predator stress in pregnant rats, rats were exposed to a hunting dog in an enclosed room. Exposure time was three 10‑min daily sessions separated by 1 h, starting at week 1 of pregnancy until delivery. Pregnant rats in the exercise group were forced to run on a treadmill for 30 min once a day, starting one week following pregnancy until delivery. Rats receiving predator stress during pregnancy exhibited PTSD anxiety‑like behaviors following delivery. Expression of 5‑hydroxytryptamine (5‑HT) and its synthesizing enzyme tryptophan hydroxylase (TPH) in the dorsal raphe was increased compared with unstressed rats. Expression of c‑Fos and neuronal nitric oxide synthases (nNOS) in the hypothalamus and locus coeruleus were higher in the rats receiving stress during pregnancy compared with unstressed rats. By contrast, treadmill exercise during pregnancy ameliorated anxiety‑like behaviors and reduced the expression of 5‑HT, TPH, c‑Fos and nNOS in the PTSD maternal rats. The results of the present study indicate that exercise during pregnancy is suitable for use as a therapeutic strategy to reduce anxiety‑related disorders, including PTSD.
Full-text · Article · Nov 2012 · Molecular Medicine Reports
[Show abstract][Hide abstract] ABSTRACT: Aims:
Parkinson's disease is a debilitating neurodegenerative disorder characterized by the gradual loss of dopaminergic neurons. We investigated the effects of treadmill exercise on dopaminergic neuronal loss and microglial activation using 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine/probenecid (MPTP/P)-induced Parkinson's disease mice.
Parkinson's disease was induced in mice by injection of MPTP/P. The mice in the exercise groups were put on a treadmill to run for 30min/day, five times per week for four weeks. Motor balance and coordination was measured using rota-rod test. Expressions of inducible nitric oxide synthase (iNOS) and phosphorylated extracellular signal-regulated kinase (p-ERK), phosphorylated NH(2)-terminal kinase (p-JNK), phosphorylated p-38 (p-p38), CD200, and CD200 receptor were determined by western blotting. Expressions of tyrosine hydroxylase (TH) and CD11b were evaluated by immunohistochemistry.
Parkinson's disease mice displayed poor motor balance and coordination with loss of nigrostriatal dopaminergic neurons. iNOS expression was enhanced via up-regulation of phosphorylated mitogen-activated protein kinases (p-MAPKs) signaling, such as p-ERK, p-JNK, and p-p-38 in the Parkinson's disease mice. Microglial activation was also observed in the Parkinson's disease mice, showing increased CD11b expression with suppressed CD200 and CD200 receptor expressions. Treadmill exercise prevented the loss of nigrostriatal dopaminergic neurons, and ameliorated the motor balance and coordination dysfunction in the Parkinson's disease mice. Treadmill exercise suppressed iNOS expression via down-regulation of MAPKs and also inhibited microglial activation in the Parkinson's disease mice.
Treadmill exercise prevented dopaminergic neuronal loss by inhibiting brain inflammation through suppression of microglial activation in the Parkinson's disease mice.
[Show abstract][Hide abstract] ABSTRACT: Hypoxic ischemia injury is a common cause of functional brain damage, resulting from a decrease in cerebral blood flow and oxygen supply to the brain. The main problems associated with hypoxic ischemia to the brain are memory impairment and dopamine dysfunction. Hypothermia has been suggested to ameliorate the neurological impairment induced by various brain insults. In this study, we investigated the effects of hypothermia on memory function and dopamine synthesis following hypoxic ischemia to the brain in rats. For this purpose, a step-down avoidance task, a radial eight-arm maze task, and immunohistochemistry for tyrosine hydroxylase (TH) and 5-bromo-2′-deoxyuridine (BrdU) were performed. The present results indicated that the hypoxic ischemia-induced disturbance of the animal's performances and spatial working memory was associated with a decrement in TH expression in the substantia nigra and striatum, and an increase in cell proliferation in the hippocampal dentate gyrus. Hypothermia treatment improved the animals’ performance and spatial working memory by suppressing the decrement in TH expression in the substantia nigra and striatum and the increase in cell proliferation in the dentate gyrus. We suggest that hypothermia can be an efficient therapeutic modality to facilitate recovery following hypoxic ischemia injury to the brain, presumably by modulating the dopaminergic cell loss.
No preview · Article · Dec 2011 · Animal cells and systems the official publication of the Zoological Society of Korea
[Show abstract][Hide abstract] ABSTRACT: Neuropathic pain remains one of the most difficult clinical pain syndromes to treat. It is traditionally viewed as being mediated solely by neurons; however, glial cells have recently been implicated as powerful modulators of pain. It is known that the analgesic effects of electroacupuncture (EA) are mediated by descending pain inhibitory systems, which mainly involve spinal opioid, adrenergic, dopaminergic, serotonergic, and cholinergic receptors. However, studies investigating the suppressive effects of EA on spinal glial activation are rare. In the present study, we assessed the cumulative analgesic effects of EA on mechanical and warm allodynia in a rat model of neuropathic pain. We investigated the clinical efficacy of EA as long-term therapy and examined its effects on spinal glia, matrix metalloproteinase (MMP)-9/MMP-2, proinflammatory cytokines and serum immunoglobulin G (IgG) concentration. Rats were randomly divided into four groups as follows: the operation group (OP), operation with EA-non acupoint (EA-NA), operation with EA-ST36 acupoint (EA-ST36), and sham operation (shamOP). Following neuropathic or sham surgery, repeated EA was performed every other day after the behavioral test. On day 53 after the behavioral test, rats were perfused for immunohistochemistry and Western blot analysis to observe quantitative changes in spinal glial markers such as OX-42, astrocytic glial fibrillary acidic protein (GFAP), MMP-9/MMP-2, and proinflammatory cytokines. Allodynia and OX-42/GFAP/MMP-9/MMP-2/tumor necrosis factor (TNF)-α/interleukin (IL)-1β activity in the EA-ST36 group was significantly reduced, compared to the OP and EA-NA groups, and IgG in EA-ST36 rats significantly increased. Our results suggest that the analgesic effect of EA may be partly mediated via inhibition of inflammation and glial activation and repeated EA stimulation may be useful for treating chronic pain clinically.
No preview · Article · Sep 2011 · Brain research bulletin
[Show abstract][Hide abstract] ABSTRACT: This study was conducted to determine the effects of Phellinus linteus (PL) on serotonin synthesis in the brain and on the expression of monocarboxylate transporters (MCTs) in muscles during exhaustive exercise in rats. In this study, 60 male Sprague-Dawley rats were divided into the following 6 groups: control; exercise; exercise and 50 mg/kg of PL treatment; exercise and 100 of mg/kg PL treatment; exercise and 200 mg/kg of PL treatment; and exercise and 100 mg/kg of caffeine treatment. Treatment with 200 mg/kg of PL led to a significant increase in the time to exhaustion in response to running on a treadmill and a significant decrease in 5-hydroxytryptamine synthesis and tryptophan hydroxylase expression in the dorsal raphe of rats. MCT1 and MCT4 expression of the gastrocnemius muscles was also increased in response to treatment with 200 mg/kg of PL. The results of the present study demonstrated that the administration of PL increased endurance exercise performance through inhibition of serotonin production in the brain and increased the expression of MCT1 and MCT4 in muscles. These results suggest that PL exerts an ergogenic effect.
No preview · Article · Feb 2011 · Journal of Nutritional Science and Vitaminology
[Show abstract][Hide abstract] ABSTRACT: Stress urinary incontinence (SUI) is a common condition that primarily affects women. Here, we investigate the effects of human adipose-derived stem cells (ADSCs) in a rodent model of SUI. Female Sprague-Dawley rats at 7 weeks of age were randomly divided into three groups (n=8 per group): sham-operation, SUI-induction by transabdominal urethrolysis, and SUI-induction followed by transplantation of human ADSCs into the urethra. The abdominal leak point pressure at 8 weeks after the operation was markedly decreased by transabdominal urethrolysis, confirming successful induction of SUI. Interestingly, transplantation of human ADSCs into the urethra significantly blunted the decrease of abdominal leak point pressure in SUI-induced rats. Accordingly, we observed expression of α-smooth muscle actin in a significant proportion of transplanted ADSCs, indicating differentiation of ADSCs into smooth muscle cells in the urethra. Moreover, the SUI-induced elevations of c-Fos immunoreactivities in the pontine micturition center (PMC) and in the ventrolateral periaqueductal gray (vlPAG) were clearly suppressed by transplantation of human ADSCs. These results imply that human ADSCs can be an effective therapeutic modality to ameliorate the symptoms of SUI.
No preview · Article · Dec 2010 · Animal cells and systems the official publication of the Zoological Society of Korea
[Show abstract][Hide abstract] ABSTRACT: Early adverse experiences resulting from maternal separation may lead to neuronal cell death and eventually cause memory impairment. Maternal separation has been used to create a valid animal model of early life stress and a depression-like syndrome. The phosphodiesterase (PDE)-5 inhibitor, tadalafil (Cialis), is a widely prescribed agent for the treatment of erectile dysfunction. In this study, we investigated the effects of tadalafil on apoptosis and cell proliferation in the hippocampal dentate gyrus of rat pups following maternal separation. Specifically, the immobility time in the forced swim test was increased in the maternal-separated rat pups, and tadalafil treatment decreased the immobility time. The rat pups in the maternal separation group had deceased memory function compared to the rat pups in the maternal care group, and tadalafil treatment increased memory function of the rat pups in the maternal separation group. Apoptotic cell death in the hippocampal dentate gyrus was significantly increased in the maternal-separated rat pups, and tadalafil treatment suppressed maternal separation-induced apoptosis. In contrast, cell proliferation in the dentate gyrus was significantly decreased in the maternal-separated rat pups, and taldalafil treatment increased cell proliferation. The present results suggest that tadalafil improves depressive symptoms and alleviates memory impairment by suppressing apoptotic neuronal cell death and enhancing cell proliferation in maternal-separated rat pups.
No preview · Article · Nov 2010 · Neuroscience Letters
[Show abstract][Hide abstract] ABSTRACT: Stressful experiences, such as an unsatisfactory mother-infant relationship after delivery, can induce depressive disorders, and it is well-known that stressors impair memory function. The hippocampus plays a crucial role in memory processes. In the present study, we determined whether a depressed-like state induced by repeated separation of pups affects the memory capability of the maternal rats. We also determined the effects of repeated separation from pups on cell proliferation, apoptosis, and serotonin expression in the brains of maternal rats. In the present results, the immobility time in the forced swim test was increased and the climbing time was decreased in the mothers separated from their pups. The latency in the step-down avoidance task was increased in the mothers separated from their pups. Also, the expressions of serotonin (5-hydroxytryptamine) and tryptophan hydroxylase in the dorsal raphe were decreased in the mothers separated from their pups. The number of Ki-67-positive cells was decreased, while the number of terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL)-positive cells in the hippocampal dentate gyrus was increased in the mothers separated from their pups. Based on the present results, it is suggested that separation of pups might induce a depressed-like state in the maternal rats with reduced cell proliferation and increased apoptosis in the hippocampus, resulting in memory impairment of maternal rats.
No preview · Article · Feb 2010 · Neuroscience Letters