Rocuronium Bromide Inhibits Inflammation and Pain by Suppressing Nitric Oxide Production and Enhancing Prostaglandin E2 Synthesis in Endothelial Cells.

PURPOSE: Rocuronium bromide is a nondepolarizing neuromuscular blocking drug and has been used as an adjunct for relaxation or paralysis of the skeletal muscles, facilitation of endotracheal intubation, and improving surgical conditions during general anesthesia. However, intravenous injection of rocuronium bromide induces injection pain or withdrawal movement. The exact mechanism of rocuronium bromide-induced injection pain or withdrawal movement is not yet understood. We investigated whether rocuronium bromide treatment is involved in the induction of inflammation and pain in vascular endothelial cells. METHODS: For this study, calf pulmonary artery endothelial (CPAE) cells were used, and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, Western blot, nitric oxide detection, and prostaglandin E2 immunoassay were conducted. RESULTS: Rocuronium bromide treatment inhibited endothelial nitric oxide synthase and suppressed nitric oxide production in CPAE cells. Rocuronium bromide activated cyclooxygenase-2, inducible nitric oxide synthase and increased prostaglandin E2 synthesis in CPAE cells. CONCLUSIONS: Rocuronium bromide induced inflammation and pain in CPAE cells. Suppressing nitric oxide production and enhancing prostaglandin E2 synthesis might be associated with rocuronium bromide-induced injection pain or withdrawal movement.

Voluntary wheel running ameliorates symptoms of MK-801-induced schizophrenia in mice.

Schizophrenia is a chronic and severe mental disorder characterized by the disintegration of cognitive thought processes and emotional responses. Despite the precise cause of schizophrenia remains unclear, it is hypothesized that a dysregulation of the N­methyl­D­aspartate (NMDA) receptor in the brain is a major contributing factor to its development. Brain­derived neurotrophic factor (BDNF) is a member of the neurotrophin family and is implicated in learning and memory processes. In the present study, we investigated in vivo the effects of voluntary wheel running on behavioral symptoms associated with NMDA receptor expression, using MK­801­induced schizophrenic mice. Abilify (aripiprazole), a drug used to treat human schizophrenia patients, was used as the positive control. For the assessment of behavioral symptoms affecting locomotion, social interaction and spatial working memory, the open­field, social interaction and Morris water maze tests were conducted. For investigating the biochemical parameters, NMDA receptor expression in the hippocampal CA2­3 regions and prefrontal cortex was detected by NMDA immunofluorescence and BDNF expression in the hippocampus was measured using western blot analysis. MK­801 injection for 14 days induced schizophrenia­like behavioral abnormalities with decreased expression of the NMDA receptor and BDNF in the brains of mice. The results indicated that free access to voluntary wheel running for 2 weeks alleviated schizophrenia­like behavioral abnormalities and increased the expression of NMDA receptor and BDNF, comparable to the effects of aripiprazole treatment. In the present study, the results suggest that NMDA receptor hypofunctioning induced schizophrenia­like behaviors, and that voluntary wheel running was effective in reducing these symptoms by increasing NMDA receptor and BDNF expression, resulting in an improvement of disease related behavioral deficits.

Psychiatric rehabilitation of emotional disorders.

Emotional disorder is psychological and behavioral problems of emotional domain that is different from cognitive domain, such as thought and memory. Typical emotional disorders are anxiety disorder, depression, and bipolar disorder. In the present study, we discussed on the symptoms, progression, and treatment for the anxiety disorder (panic disorder, social phobia, and obsessive compulsive disorder), depression, and bipolar disorder. The goal of treatment for the emotional disorder is removal of symptoms. In spite of the development of brain science, removal of symptoms, prevention of recurrence, and coming back to normal life require patience and effort.

Treadmill exercise inhibits hippocampal apoptosis through enhancing N-methyl-D-aspartate receptor expression in the MK-801-induced schizophrenic mice.

Schizophrenia is a severe mental disorder characterized by abnormal mental functioning and disruptive behaviors. Abnormal expression of N-methyl-D-aspartate (NMDA) receptor, one of the glutamate receptor subtypes, has also been suggested to contribute to the symptoms of schizophrenia. The effect of treadmill exercise on schizophrenia-induced apoptosis in relation with NMDA receptor has not been evaluated. In the present study, we investigated the effect of treadmill exercise on neuronal apoptosis in the hippocampus using MK-801-induced schizophrenic mice. MK-801 was intraperitoneally injected once a day for 2 weeks. The mice in the exercise groups were forced to run on a treadmill exercise for 60 min, once a day for 2 weeks. In the present results, repeated injection of the NMDA receptor antagonist MK-801 reduced expression of NMDA receptor in hippocampal CA2-3 regions. MK-801 injection increased casapse-3 expression and enhanced cytochrome c release in the hippocampus. The ratio of Bax to Bcl-2 was higher in the MK-801-induced schizophrenia mice than the normal mice. In contrast, treadmill exercise enhanced NMDA receptor expression, suppressed caspae-3 activation and cytochrome c release, and inhibited the ratio of Bax to Bcl-2. Based on present finding, we concluded that NMDA receptor hypofunctioning induced neuronal apoptosis in MK-801-induced schizophrenic mice. Treadmill exercise suppressed neuronal apoptosis through enhancing NMDA receptor expression in schizophrenic mice.

Psychopathology of social isolation.

The most important defining factor of being human is the use of symbolic language. Language or communication problem occurs during the growth, the child will have a higher risk of social isolation and then the survival will be threatened constantly. Today, adolescents and youths are familiar with computer and smart-phone devices, and communication with others by these devices is easy than face-to-face communication. As adolescents and youths live in the comfortable and familiar cyber-world rather than actively participating real society, so they make social isolation. Extreme form of this isolation in adolescents and youths is so-called Socially Withdrawn Youth. In this study, the psychopathological factors inducing social isolation were discussed. Development stages of social isolation in relation with types of social isolation, Ego-syntonic isolation and Ego-dystonic isolation, were also considered.

Treadmill exercise ameliorates disturbance of spatial learning ability in scopolamine-induced amnesia rats.

Alzheimer's disease is the most common neurodegenerative disease and this disease induces progressive loss of memory function Scopolamine is a non-selective muscarinic cholinergic receptor antagonist and it induces impairment of learning ability. Exercise is known to ameliorate memory deficits induced by various brain diseases. In the present study, we investigated the effect of treadmill exercise on spatial learning ability in relation with cell proliferation in the hippocampus using the scopolamine-induced amnesia mice. For the induction of amnesia, 1 mg/kg scopolamine hydrobromide was administered intraperitoneally once a day for 14 days. Morris water maze test for spatial learning ability was conducted. Immonofluorescence for 5-bromo-2-deoxyuri-dine (BrdU) and western blot for brain-derived neurotrophic factor (BDNF) and its receptor tyrosine kinase B (TrkB) were performed. In the present results, scopolamine-induced amnesia mice showed deterioration of spatial learning ability. Inhibition of cell proliferation and suppression of BDNF and TrkB expressions were observed in the scopolamine-induced amnesia mice. Treadmill exercise improved spatial learning ability and increased cell proliferation through activating of BDNF-TrkB pathway in the amnesia mice. These findings offer a possibility that treadmill exercise may provide preventive or therapeutic value for the memory loss induced by variable neurodegenerative diseases including Alzheimer's disease.

Treadmill exercise improves spatial learning ability by enhancing brain-derived neurotrophic factor expression in the attention-deficit/hyperactivity disorder rats.

Attention-deficit/hyperactivity disorder (ADHD) patients show learning difficulty and impulsiveness. Exercise is known to improve learning ability and memory function. In the present study, we investigated the duration-dependence of the effect of treadmill exercise on spatial learning ability in relation with brain-derived neurotrophic factor (BDNF) expression in ADHD rats. For this study, radial 8-arm maze test and western blot for BDNF and tyrosine kinase B (TrkB) were performed. Spontaneous hypertensive rats were used as the ADHD rats and Wistar-Kyoto rats were used as the control rats. The rats in the exercise groups were forced to run on a treadmill for 10 min, 30 min, and 60 min once a day for 28 consecutive days. ADHD rats displayed impairment of spatial learning ability, in contrast treadmill exercise ameliorated impairment of spatial learning ability. Treadmill exercise for 30 min per day showed most potent ameliorating effect on impairment of spatial learning ability. BDNF and TrkB expressions in the hippocampus were decreased in the ADHD rats, in contrast treadmill exercise enhanced BDNF and TrkB expressions. Treadmill exercise for 30 min and for 60 min per day showed enhancing effects on BDNF and TrkB expressions. Treadmill exercise alleviated deficits in the spatial learning ability through enhancing BDNF and TrkB expressions in the ADHD rats. Treadmill exercise for 30 min per day can be considered as the most effective therapeutic modality for the ADHD symptoms.

Treadmill exercise ameliorates short-term memory disturbance in scopolamine-induced amnesia rats.

PURPOSE: Scopolamine is a nonselective muscarinic cholinergic receptor antagonist, which induces impairment of learning ability and memory function. Exercise is known to ameliorate brain disturbance induced by brain injuries. In the present study, we investigated the effect of treadmill exercise on short-term memory in relation to acetylcholinesterase (AChE) expression in the hippocampus, using a scopolamine-induced amnesia model in mice. METHODS: To induce amnesia, 1 mg/kg scopolamine hydrobromide was administered intraperitoneally once per day for 14 days. A step-down avoidance test for short-term memory was conducted. AChE histochemistry, immunohistochemistry for collagen IV, and doublecortin were performed. RESULTS: Short-term memory deteriorated in the mice with scopolamine-induced amnesia, concomitant with enhanced AChE expression and suppression of angiogenesis in the hippocampus. Critically, treadmill exercise ameliorated short-term memory impairment, suppressed AChE expression, and enhanced angiogenesis in the mice with scopolamine-induced amnesia. CONCLUSIONS: Overexpression of AChE is implicated in both brain and renal disease. The findings of our study indicate that treadmill exercise may be of therapeutic value in neurodegenerative and renal diseases by suppressing the effects of AChE expression.

Treadmill exercise improves short-term memory by enhancing neurogenesis in amyloid beta-induced Alzheimer disease rats.

Alzheimer's disease is one of the most devastating neurodegenerative disorders, and this disease is characterized by severe memory impairment and decline of cognition. Hippocampal neurons are vulnerable to injury induced by Alzheimer's disease. Physical exercise is known to promote cell survival and functional recovery after brain injuries. In the present study, we investigated the effects of treadmill exercise on short-term memory in relation with neurogenesis in the rats with amyloid ß25-35 (Aß25-35)-induced Alzheimer's disease. The rat model of Alzheimer's disease was induced by the intracerebroventricular (ICV) injection of Aß25-35, using a stereotaxic instrument. The rats in the exercise group were forced to run on a treadmill for 30 min once daily for 4 consecutive weeks, starting 2 days after Aß25-35 injection. Presently, short-term memory was deteriorated and apical dendritic length in the hippocampus was shortened in the hippocampus by Aß25-35 injection. In contrast, treadmill exercise alleviated memory impairment and increased apical dendritic length in the Aß25-35-injected rats. Neurogenesis and brain-derived neurotorphic factor (BDNF) and tyrosine kinase B (trkB) in the hippocampal dentate gyrus were decreased by Aß25-35 injection. Treadmill exercise increased neurogenesis and expressions of BDNF and trkB expressions. The present study shows that treadmill exercise may provide therapeutic value for the alleviating symptoms of Alzheimer's disease.

Treadmill exercise reduces spinal cord injury-induced apoptosis by activating the PI3K/Akt pathway in rats.

Apoptosis occurring secondary to spinal cord injury (SCI) causes further neural damage and functional loss. In this study, a rat model was used to investigate the effect of treadmill exercise on SCI-induced apoptosis and expression of neurotrophic factors. To produce SCI, a contusion injury (10 g × 25 mm) was applied subsequent to laminectomy at the T9-T10 level. Following SCI, treadmill exercise was performed for six weeks. Hindlimb motor function was evaluated with a grid-walking test. The expression of neurotrophic factors and the level of apoptosis at the site of SCI were determined by western blotting. SCI reduced hindlimb motor function and suppressed expression of neurotrophin (NT)-3 and insulin-like growth factor (IGF)-1. Expression of phosphatidylinositol 3-kinase (PI3K), the ratio of phosphorylated Akt to Akt (pAkt/Akt) and the ratio of B-cell lymphoma 2 (Bcl-2) to Bax (Bcl-2/Bax) were decreased, and cleaved caspase-3 expression was increased by SCI. Treadmill exercise enhanced hindlimb motor function and increased expression of nerve growth factor (NGF), NT-3 and IGF-1 in the SCI rats. Treadmill exercise increased PI3K expression, the pAkt/Akt and the Bcl-2/Bax ratios, and suppressed cleaved caspase-3 expression in the injured spinal cord. This study demonstrated that treadmill exercise promotes the recovery of motor function by suppressing apoptosis in the injured spinal cord. The beneficial effect of exercise may be attributed to the increase in expression of neurotrophic factors via activation of the PI3K/Akt pathway.

Exposure to music and noise during pregnancy influences neurogenesis and thickness in motor and somatosensory cortex of rat pups.

PURPOSE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: Our study suggests that music and noise during the developmental period are important factors influencing brain development and urogenital disorders.

Impact of Several Types of Stresses on Short-term Memory and Apoptosis in the Hippocampus of Rats.

PURPOSE: Stress has a deteriorating effect on hippocampal function. It also contributes to symptom exacerbation in many disease states, including overactive bladder and interstitial cystitis/bladder pain syndrome. We investigated the effects of various types of stresses (restraint, noise, and cold) on short-term memory and apoptosis in relation with corticotropin-releasing factor (CRF) expression. METHODS: Rats in the restraint stress group were restrained in a transparent Plexiglas cylinder for 60 minutes twice daily. Rats in the noise stress group were exposed to the 120 dB supersonic machine sound for 60 minutes twice daily. Rats in the cold stress group were placed in a cold chamber at 4℃ for 60 minutes twice daily. Each stress was applied for 10 days. A step-down avoidance test for short-term memory, immunohistochemistry for caspase-3 expression, and western blot analysis for Bax and Bcl-2 expressions were conducted. RESULTS: Latency time was decreased and CRF expression in the hippocampal dentate gyrus and hypothalamic paraventricular nucleus were increased in all of the stress groups. The number of caspase-3-positive cells in the hippocampal dentate gyrus was increased and the expressions of Bax and Bcl2 in the hippocampus were decreased in all of the stress groups. CONCLUSIONS: All of the stress groups experienced short-term memory impairment induced by apoptosis in the hippocampus. The present results suggest the possibility that these stresses affecting the impairment of short-term memory may also induce functional lower urinary tract disorders.

The phosphodiesterase type-5 inhibitor, tadalafil, improves depressive symptoms, ameliorates memory impairment, as well as suppresses apoptosis and enhances cell proliferation in the hippocampus of maternal-separated rat pups.

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.

The Relationship between Empathy and Medical Education System, Grades, and Personality in Medical College Students and Medical School Students.

PURPOSE: This study investigated the relationship between empathy and medical education system, grades, and personality in medical college (MC) students and medical school (MS) students. METHODS: One hundred fifty-five MC students and 137 MS students participated in this study, completing questionnaires on sociodemographic data, Jefferson Scale of Empathy, S-version, Korean edition (JSE-S-K), and Temperament and Character Inventory (TCI). RESULTS: Reward Dependence (RD), Cooperativeness (C), and Self-directedness+ Cooperativeness (SC), which are subscales of the TCI, correlated significantly with JSE-S-K score. Third-year students had significantly higher scores on the JSE-S-K than first-year students. MS students had significantly higher scores on the JSE-S-K and the SC subscale of the TCI than MC students. However, there were no significant differences in empathy with regard to age, sex, motivation toward medical science, club activity, and applied specialty. CONCLUSION: These results suggest that empathy is associated with personality traits, such as RD, C, and SC, and medical education curriculum contributes incrementally to empathy for students. The difference in test scores for empathy between MC students and MS students might be due to differences in personality traits, such as SC.