Jun-Jang Jin

Dexmedetomidine ameliorates intracerebral hemorrhage-induced memory impairment by inhibiting apoptosis and enhancing brain-derived neurotrophic factor expression in the rat hippocampus.

Intracerebral hemorrhage (ICH) is a severe type of stroke causing neurological dysfunction with a high mortality rate. Dexmedetomidine is an agonist for α2‑adrenoreceptors with sedative, anxiolytic, analgesic and anesthetic effects. In the present study, we investigated the effects of dexmedetomidine on short‑term and spatial learning memory, as well as its effects on apoptosis following the induction of ICH in rats. A rat model of IHC was created by an injection of collagenase into the hippocampus using a stereotaxic instrument. Dexmedetomidine was administered intraperitoneally daily for 14 consecutive days, commencing 1 day after the induction of ICH. The step‑down avoidance test for short‑term memory and the radial 8‑arm maze test for spatial learning memory were conducted. Terminal deoxynucleotidyl transferase‑mediated dUTP nick end-labeling (TUNEL) assay, immunohistochemistry for caspase‑3, and western blot analysis for Bcl‑2, Bax, Bid and caspase-3 expression were performed for the detection of apoptosis in the hippocampus. Western blot analysis for the brain‑derived neurotrophic factor (BDNF) and tyrosine kinase B (TrkB) was also performed for the detection of cell survival in the hippocampus. The induction of ICH deteriorated short‑term and spatial learning memory, increased apoptosis and suppressed BDNF and TrkB expression in the hippocampus. Treatment with dexmedetomidine ameliorated the ICH‑induced impairment of short‑term and spatial learning memory by suppressing apoptosis and enhancing BDNF and TrkB expression. In the normal rats, dexmedetomidine exerted no significant effects on memory function and apoptosis. The present results suggest the possibility that dexmedetomidine may be used as a therapeutic agent for the conservation of memory function in stroke patients.

Adenosine A2A-receptor agonist polydeoxyribonucleotide promotes gastric ulcer healing in Mongolian gerbils

Polydeoxyribonucleotide (PDRN) interacts with the adenosine A2A-receptor and stimulates vascular endothelial growth factor (VEGF) expression. While it has been indicated that PDRN might accelerate wound healing, its impact on gastric ulcers (GU) is still unknown. We investigated the effects of PDRN on VEGF expression in relation to inflammation and apoptosis in GU by using Mongolian gerbils. GU was induced by injection of acetic acid into the subserosal surface of the stomach. The gerbils in the PDRN-treated groups received daily intraperitoneal injections of PDRN over 2 weeks. Reverse transcriptase-polymerase chain reaction (RT-PCR) for tumor necrosis factor-alpha (TNF-α), interleukin (IL)-1β, and IL-6, as well as terminal deoxynucleotidyltransferase-mediated dUTP nick-end labeling (TUNEL) assay, immunohistochemistry for caspase-3, and western blot for VEGF, Bax, and Bcl-2 were conducted. Acetic acid injection induced GU, and VEGF expression in the gastric mucosa was enhanced by GU. PDRN treatment decreased ulcer size and led to overexpression of VEGF in GU. Expression of TNF-α, IL-1β, and IL-6 was increased in GU, and PDRN treatment decreased the expression of these cytokines. The numbers of TUNEL-positive and caspase-3-positive cells were increased by GU, while PDRN reduced these numbers. Induction of GU enhanced the ratio of Bax to Bcl-2, while PDRN diminished this ratio. Overexpression of VEGF and inhibition of inflammation and apoptosis by PDRN may be the underlying mechanisms of PDRN action on GU healing.

Swimming exercise ameliorates multiple sclerosis-induced impairment of short-term memory by suppressing apoptosis in the hippocampus of rats

Multiple sclerosis is one of the autoimmune diseases in the central nervous system. Multiple sclerosis occurs through multiple mechanisms, and it is also mediated in part by an apoptotic mechanism. Swimming exercise has been recommended for the prevention and treatment of chronic diseases. In the present study, we investigated the effects of swimming exercise on short-term memory in relation with apoptotic neuronal cell death in the hippocampus following induction of multiple sclerosis. For this study, step-down avoidance task, terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay, immunohistochemistry for caspase-3 were performed. The animal model of multiple sclerosis was made by bilateral intracerebral ventricle injection of ethidium bromide. The rats in the swimming exercise groups were forced to swim for 30 min once daily for 14 consecutive days, starting 3 days after induction of multiple sclerosis. In the present results, short-term memory was deteriorated in the multiple sclerosis-induced rats. The number of TUNEL-positive and caspase-3-positive cells in the hippocampal dentate gyrus was increased in the multiple sclerosis-induced rats. Swimming exercise alleviated multiple sclerosis-induced short-term memory impairment by suppressing apoptotic neuronal cell death in the hippocampus. These effects of swimming exercise may aid symptom relief in the incurable neurodegenerative diseases.

The effect of horse simulator riding on visual analogue scale, body composition and trunk strength in the patients with chronic low back pain

Chronic low back pain (CLBP) is one of the most common musculoskeletal disorders, and thus effective treatments are required. Recently, a real horseback riding has been reported to be beneficial for the patients. However, it has some limitations, such as limited approaches and safety issues.

Dexmedetomidine, α2-adrenoceptor agonist, does not induce apoptosis in the brachial plexus of rats

Dexmedetomidine (Precedex) is a selective α2-adrenoceptor agonist that shows opioid-sparing effects with reduced inhalational anesthetic requirement. Since the possibility that dexmedetomidine could induce nerve degeneration has not been completely ruled out, we evaluated whether it can induce apoptosis in rats when used in a nerve block. We performed hematoxylin and eosin staining, terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assays, immunohistochemistry for caspase-3 and neurofilament, and western blotting for BAX, Bcl-2, and nerve growth factor (NGF) in the brachial plexus of rats. The axillary brachial plexus was carefully exposed and 100 μl (40 µg/kg) dexmedetomidine was administered directly. Rats were sacrificed at 6 h, 12 h, or 24 h after dexmedetomidine administration. In the present study, dexmedetomidine did not exert any effects on histological findings and neurofilament expression. The number of TUNEL-positive and caspase-3-positive cells in the brachial plexus did not change following dexmedetomidine administration. The Bcl-2 to BAX ratio temporarily increased and then returned to the control level at 24 h after dexmedetomidine administration. Expression of NGF in the brachial plexus temporarily increased and then returned to the control level 12 h after dexmedetomidine administration. The results of our study demonstrated that dexmedetomidine did not induce apoptosis and degeneration when used in the brachial plexus.

Aqueous extract of Cordyceps alleviates cerebral ischemia-induced short-term memory impairment in gerbils

Cerebral ischemia is caused by reduced cerebral blood flow due to a transient or permanent cerebral artery occlusion. Ischemic injury in the brain leads to neuronal cell death, and eventually causes neurological impairments. Cordyceps, the name given to the fungi on insects, has abundant useful natural products with various biological activities. Cordyceps is known to have nephroprotective, hepatoprotective, anti-inflammatory, antioxidative, and antiapoptotic effects. We investigated the effects of Cordyceps on short-term memory, neuronal apoptosis, and cell proliferation in the hippocampal dentate gyrus following transient global ischemia in gerbils. For this study, a step-down avoidance test, terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling assay, immunohistochemistry for caspase-3 and 5-bromo-2′-de-oxyuridine, and western blot for Bax, Bcl-2, brain-derived neurotrophic factor (BDNF), and tyrosin kinase B were performed. In the present study, Cordyceps alleviated cerebral ischemia-induced short-term memory impairment. Cordyceps showed therapeutic effects through inhibiting cerebral ischemia-induced apoptosis in the hippocampus. Cordyceps suppressed cerebral ischemia-induced cell proliferation in the hippocampal dentate gyrus due to the reduced apoptotic neuronal cell death. Cordyceps treatment also enhanced BDNF and TrkB expressions in the hippocampus of ischemic gerbils. It can be suggested that Cordyceps overcomes cerebral ischemia-induced neuronal apoptosis, thus facilitates recovery following cerebral ischemia injury.

Oral mucosa stem cells alleviates spinal cord injury-induced neurogenic bladder symptoms in rats

BackgroundSpinal cord injury (SCI) deteriorates various physical functions, in particular, bladder problems occur as a result of damage to the spinal cord. Stem cell therapy for SCI has been focused as the new strategy to treat the injuries and to restore the lost functions. The oral mucosa cells are considered as the stem cells-like progenitor cells. In the present study, we investigated the effects of oral mucosa stem cells on the SCI-induced neurogenic bladder in relation with apoptotic neuronal cell death and cell proliferation.ResultsThe contraction pressure and the contraction time in the urinary bladder were increased after induction of SCI, in contrast, transplantation of the oral mucosa stem cells decreased the contraction pressure and the contraction time in the SCI-induced rats. Induction of SCI initiated apoptosis in the spinal cord tissues, whereas treatment with the oral mucosa stem cells suppressed the SCI-induced apoptosis. Disrupted spinal cord by SCI was improved by transplantation of the oral mucosa stem cells, and new tissues were increased around the damaged tissues. In addition, transplantation of the oral mucosa stem cells suppressed SCI-induced neuronal activation in the voiding centers.ConclusionsTransplantation of oral mucosa stem cells ameliorates the SCI-induced neurogenic bladder symptoms by inhibiting apoptosis and by enhancing cell proliferation. As the results, SCI-induced neuronal activation in the neuronal voiding centers was suppressed, showing the normalization of voiding function.

Polydeoxyribonucleotide Ameliorates Lipopolysaccharide-Induced Lung Injury by Inhibiting Apoptotic Cell Death in Rats

Lung injury is characterized by diffuse lung inflammation, alveolar-capillary destruction, and alveolar flooding, resulting in respiratory failure. Polydexyribonucleotide (PDRN) has an anti-inflammatory effect, decreasing inflammatory cytokines, and suppressing apoptosis. Thus, we investigated its efficacy in the treatment of lung injury, which was induced in rats using lipopolysaccharide (LPS). Rats were randomly divided into three groups according to sacrifice time, and each group split into control, lung injury-induced, and lung injury-induced + PDRN-treated groups. Rats were sacrificed 24 h and 72 h after PDRN administration, according to each group. Lung injury was induced by intratracheal instillation of LPS (5 mg/kg) in 0.2 mL saline. Rats in PDRN-treated groups received a single intraperitoneal injection of 0.3 mL distilled water including PDRN (8 mg/kg), 1 h after lung injury induction. Percentages of terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL)-positive, cleaved caspase-3-, -8-, and -9-positive cells, the ratio of Bcl-2-associated X protein (Bax) to B-cell lymphoma 2 (Bcl-2), and expressions of inflammatory cytokines (tumor necrosis factor-α, interleukin-6) were decreased by PDRN treatment in the LPS-induced lung injury rats. Therefore, treatment with PDRN reduced lung injury score. This anti-apoptotic effect of PDRN can be ascribed to the enhancing effect of PDRN on adenosine A2A receptor expression. Based on these results, PDRN might be considered as a new therapeutic agent for the treatment of lung injury.

Time-effects of horse simulator exercise on psychophysiological responses in men with chronic low back pain

BACKGROUND: Although horse simulator riding is very beneficial for patients with several diseases, there are few studies relating to treating patients with chronic low back pain (CLBP) specifically in terms of physiological and psychological outcome measures. It also has not been medically verified yet on the aspects of psychological responses and physiological changes. As well as there are not known how it can decrease the pain, how it can increase the physical conditioning, and how much good time rides a horse simulator. OBJECTIVE: To investigate the time-effects of an 8 week horse simulator exercise on body composition, visual analogue scale (VAS), and isokinetic torques of the trunk and hip joints in patients with CLBP. METHODS: Forty one young men presenting with CLBP were divided into 4 groups: LBP control group (LCG), LBP horse simulator 10 min riding group (LHS10G), LBP horse simulator 20 min riding group (LHS20G), and LBP horse simulator 30 min riding group (LHS30G), respectively. Three horse simulator exercise groups completed a rehabilitation exercise protocol for 5 days per week during 8 weeks. VAS was used to measure the severity of CLBP and functional disability for checking psychological responses. Body composition measured by bioelectrical analyzer and isokinetic torques were used to consider the physiological pre-post changes. RESULTS: Compared with the baseline, the body composition indices did not change significantly. However, muscle mass and fat mass showed increasing and decreasing tendencies in the LHS30G. The VAS indices showed significant decrease in back pain including other 12 items. A significant decrease was observed for all items except for drug relief. Especially, most of items in the LHS20G were lower than those of the other groups in the post hoc comparison. The horse simulator exercise enhanced the isokinetic strength of trunk and hip muscles. Due to the increased strength, trunk flexor/extensor ratio, hip flexor/extensor ratio, and hip abductor/adductor were close to reference values. The deficit in the ratio scores: hip flexor and extensor and hip abductor and adductor evened out after an experiment. Especially, these improvements were associated particularly with LHS20G. CONCLUSIONS: The horse simulator exercise positively affected psychophysiological responses in patients with CLBP. However, with respect to pain, the 20 min horseback riding group was associated with the best results.

Age-dependent differences of treadmill exercise on spatial learning ability between young- and adult-age rats

The effect of exercise, which increases hippocampal neurogenesis and improves memory function, is well documented, however, differences in the effect of exercise on young children and adults are not yet known. In the present study, age-dependent differences of treadmill exercise on spatial learning ability between young- and adult-age rats were investigated. The rats in the exercise groups were forced to run on a motorized treadmill for 30 min once a day for 6 weeks. Radial 8-arm maze test was conducted for the determination of spatial learning ability. Cell proliferation in the hippocampal dentate gyrus was determined by 5-bromo-2′-deoxyuridine immunohistochemistry. Western blot for brain-derived neurotrophic factor (BDNF) and tyrosine kinase B (TrkB) was performed. In the present study, the number of errors in the young-age rats was effectively decreased by treadmill exercise. Hippocampal neurogenesis was more active in the young-age rats than in the adult-age rats. BDNF and TrkB expression in the hippocampus was greater in the adult-age rats than in the young-age rats. The results of this study showed that adults have excellent spatial learning abilities than children, but the improvement of exercise-induced spatial learning ability through neurogenesis is better in children.