OBJECTIVES: The purpose of this study was to investigate the deficits in executive function in children with ADHD and anxiety disorder, and further, to characterize executive function deficits among the two groups. METHODS: Subjects consisted of 60 children between the ages of 5 and 14 (16 Normal, 24 ADHD, 20 Anxiety Disorder). Neuropsychological tests (KEDI-WISC, CCTT, STROOP, WCST, ROCF) for assessing cognitive and executive function were individually administered to all subjects. RESULTS: There were no significant differences in FSIQ or PIQ among the three groups. However, the ADHD group tended to score lower on the VIQ and subtest of similarity, vocabulary, and digit span tests. The three groups did not significantly differ with respect to CCTT test results. On the STROOP test, the ADHD group showed poor performance on the word, color, and color-word subtests. The three groups did not exhibit significant differences in WCST test results ; however, the anxiety group performed poorly belonging to below 25 percentile rank on perseverative response. On the ROCF test, the ADHD group performed poorly with respect to their organization score and in particular, regarding copy and immediate recall. The anxiety group also performed poorly with regard to organization ; however, this was limited only to immediate recall. CONCLUSION: Children with ADHD displayed poor inhibition and organizational abilities compared to children with anxiety and normal controls. Further, children with anxiety disorder exhibited low cognitive flexibility and voluntary problem-solving abilities compared to ADHD children and normal controls. Based on these results, we suggest that the characteristics of executive dysfunction in ADHD and anxiety disorder in children are different.
Anxiety ; Anxiety Disorders ; Child ; Coat Protein Complex I ; Executive Function ; Humans ; Memory, Short-Term ; Neuropsychological Tests ; Pliability ; Stroop Test ; Vocabulary

Purpose: Poloxamer-407 (P-407) is used to induce hyperlipidemia. Exercise is effective in improving arteriosclerosis and cognitive impairment. In this research, the effect of treadmill running on short-term memory in the P-407-treated hyperlipidemia rats was studied focusing on neuroinflammation. Methods: Rats were classified in normal group, normal and treadmill exercise group, P-407-treated group, and P-407-treated and treadmill exercise group. Hyperlipidemia rats were made by single intraperitoneal injection with P-407 (500 mg/kg). Treadmill exercise was conducted for 30 minutes once a day, 5 days per week during 28 days. Step-down avoidance task was done to measure short-term memory. Glial fibrillary acidic protein and ionized calcium binding adaptor molecule 1 were assessed by immunohistochemistry. Expression of adhesion molecules and proinflammatory cytokines was determined by western blot analysis. Results: Treadmill exercise alleviated lipid profiles in the P-407-induced hyperlipidemia rats. Treadmill exercise improved short-term memory, inhibited reactive astrogliosis and microglia activation, and suppressed expression of adhesion molecules and proinflammatory cytokines in the hyperlipidemic rats. Conclusions Treadmill exercise exerts alleviating effect on memory deficits by inhibiting hippocampal neuroinflammation in the hyperlipidemia. The current results suggest that treadmill running serves as the treatment strategy for the cognitive dysfunction caused by hyperlipidemia.

Amygdalin is known as vitamain B17, and it was called laetrile. Amygdalin is composed of two molecules of glucose, one molecule of benzaldehyde which induces an analgesic action, and one molecule of hydrocyanic acid which is an anti-neoplastic compound. Amygdalin had been used to treat cancers and relieve pain. In order to evaluate whether the analgesic action of amygdalin is related with descending pain control system, we performed patch clamp study. In the present study, the modulatory effects of amygdalin on glycine- and glutamate-induced ion currents in periaqueductal gray (PAG) neurons were investigated using the nystatin-perforated patch clamp method. Continuous application of lipopolysaccharides (LPS) on PAG neurons resulted in increased glycine-induced ion current, and in decreased glutamate-induced ion current. In contrast, continuous application of amygdalin with LPS resulted in decreased glycine-induced ion current increased by LPS, and increased glutamate- induced ion current decreased by LPS in concentration- and time-dependent fashion. These results demonstrate that amygdalin modulates neuronal activity of PAG by modulation of glycine and glutamate. Based on the present results, it can be suggested that amygdalin participates in the regulation of the descending pain control system in the level of PAG neurons. The present study demonstrated that activation of the descending pain control system is one of the possible analgesic mechanisms of amygdalin.
Amygdalin ; Animals ; Benzaldehydes ; Cyclooxygenase 2 ; Glucose ; Glutamic Acid ; Glycine ; Hydrogen Cyanide ; Lipopolysaccharides ; Neurons ; Periaqueductal Gray ; Rats

PURPOSE: Berberine is a type of isoquinoline alkaloid that has been used to treat various diseases. A neuroprotective effect of berberine against cerebral ischemia has been reported; however, the effects of berberine on apoptosis in relation to reactive astrogliosis and microglia activation under ischemic conditions have not yet been fully evaluated. In the present study, we investigated the effects of berberine on global ischemia-induced apoptosis, and focused on the phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) signaling pathway in the hippocampus using gerbils. METHODS: Gerbils received berberine orally once a day for 14 consecutive days, starting one day after surgery. In this study, a step-down avoidance task was used to assess short-term memory. Furthermore, we employed the terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay to evaluate DNA fragmentation, immunohistochemistry to investigate glial fibriallary acidic protein, CD11b, and caspase-3, and western blot to assess PI3K, Akt, Bax, Bcl-2, and cytochrome c. RESULTS: Our results revealed that berberine treatment alleviated ischemia-induced short-term memory impairment. Treatment with berbeine also attenuated ischemia-induced apoptosis and inhibited reactive astrogliosis and microglia activation. Furthermore, berberine enhanced phospho-PI3K and phospho-Akt expression in the hippocampus of ischemic gerbils. CONCLUSIONS: Berberine exerted a neuroprotective effect against ischemic insult by inhibiting neuronal apoptosis via activation of the PI3K/Akt signaling pathway. The antiapoptotic effect of berberine was achieved through inhibition of reactive astrogliosis and microglia activation. Berberine may therefore serve as a therapeutic agent for stroke-induced neurourological problems.
Apoptosis* ; Berberine* ; Blotting, Western ; Brain Ischemia ; Caspase 3 ; Cytochromes c ; DNA Fragmentation ; Gerbillinae ; Hippocampus ; Immunohistochemistry ; Memory, Short-Term ; Microglia ; Neurons ; Neuroprotective Agents ; Phosphatidylinositol 3-Kinases ; Phosphotransferases*

Armeniacae semen has been used in traditional medicine for the treatment of pain and inflammatory diseases. Amygdalin is the major compound of Armeniacae semen, and it is used for treatment of pain and cancers. In the present study, we compared the effects of aqueous extract of Armeniacae semen and a solution of amygdalin extracted from Armeniacae semen on the lipopolysaccharide (LPS)-stimulated cyclooxygenase-1 (COX-1), cyclooxygenase-2 (COX-2), and inducible nitric oxide synthase (iNOS) mRNA expressions in mouse BV2 microglial cells. We also compared the effects of these compounds on the prostaglandin E2 synthesis and the nitric oxide production in mouse BV2 microglial cells. In the present results, Armeniacae semen and amygdalin suppressed prostaglandin E2 synthesis and nitric oxide production by inhibiting the LPS-induced enhancement of COX-2 mRNA and iNOS mRNA expressions in mouse BV2 cells. For the COX-1 expression, Armeniacae semen showed more potent suppression effect compared to the amygdalin. However, amygdalin more potently suppressed the LPS-induced COX-2 mRNA expression compared to aqueous extract of Armeniacae semen. In the case of iNOS mRNA expression, Armeniacae semen and amygdalin showed similar suppressing effects. For the LPS-induced PGE2 synthesis, amygdalin showed more potent suppressing effect, meanwhile, Armeniacae semen and amygdalin showed similar suppressing effect on NO production. Based on the present results, amygdalin may exert anti-inflammatory and analgesic effect though mainly the inhibition of COX-2 pathway, in contrast Armeniacae semen may exert such effect though both the inhibition of COX-2 and iNOS pathways.
Amygdalin ; Animals ; Cyclooxygenase 1 ; Cyclooxygenase 2 ; Dinoprostone ; Medicine, Traditional ; Mice ; Nitric Oxide ; Nitric Oxide Synthase Type II ; Prostaglandin-Endoperoxide Synthases ; RNA, Messenger ; Semen

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.
Anesthesia, General ; Blotting, Western ; Cyclooxygenase 2 ; Dinoprostone* ; Endothelial Cells* ; Immunoassay ; Inflammation* ; Injections, Intravenous ; Intubation, Intratracheal ; Muscle, Skeletal ; Neuromuscular Blockade ; Nitric Oxide Synthase Type II ; Nitric Oxide Synthase Type III ; Nitric Oxide* ; Paralysis ; Pulmonary Artery ; Relaxation

PURPOSE: Cerebral ischemia leads to neuronal cell death, and eventually causes neurological impairments. Tadalafil is a long-acting phosphodiesterase type-5 (PDE-5) inhibitor, and it has been used for the treatment of erectile dysfunction. In the present study, we investigated whether tadalafil has the protective effect on apoptotic neuronal cell death in the motor cortex following transient global ischemia in gerbils. MATERIALS AND METHODS: For this study, Mongolian gerbils were used for the experimental animals, and transient global ischemia was induced to the gerbils by occlusion of both common carotid arteries for 7 min. Gerbils were randomly divided into five groups (n=8 in each group): the sham-operation group, the cerebral ischemia-induced group, the cerebral ischemia-induced and 0.1 mg/kg tadalafil-treated group, the cerebral ischemia-induced and 1 mg/kg tadalafil-treated group, the cerebral ischemia-induced and 10 mg/kg tadalafil-treated group. Tadalafil-treated groups received tadalafil orally once a day for a 7 consecutive days, starting one day after surgery. Terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay and immunohistochemistry for caspase-3 were performed for the detection of apoptotic neuronal cell death in the motor cortex. RESULTS: The number of TUNEL-positive cells was 21.45+/-3.69/section in the sham-operation group, 771.66+/-97.25/section in the cerebral ischemia-induced group, 688.44+/-81.35/section in the cerebral ischemia-induced and 0.1 mg/kg tadalafil-treated group, 295.66+/-36.34/section in the cerebral ischemia-induced and 1 mg/kg tadalafil-treated group, and 198.47+/-25.25/section in the cerebral ischemia-induced and 10 mg/kg tadalafil-treated group. In the present results, induction of ischemic injury increased apoptotic neuronal cell death in the motor cortex of gerbils. However, tadalafil treatment suppressed the cerebral ischemia-induced apoptotic neuronal cell death in the motor cortex as dose-dependently. CONCLUSIONS: Here in this study, we showed that tadalafil has protective effect on the cerebral ischemia-induced apoptotic neuronal cell death, and thus this drug may facilitate the recovery following ischemic cerebral injury.
Animals ; Apoptosis ; Brain Ischemia ; Carbolines ; Carotid Artery, Common ; Caspase 3 ; Cell Death ; Erectile Dysfunction ; Gerbillinae ; Immunohistochemistry ; Ischemia ; Male ; Motor Cortex ; Neurons ; Polyenes ; Tadalafil

PURPOSE: Cyclosporine A (CsA) is a potent immunosuppressive agent, and it has been used to prevent rejection of transplanted organs and to treat autoimmune diseases. Many side effects of CsA, including various types of endothelial dysfunction, have been reported. Pentoxifylline (PTX) is a non-selective phosphodiesterase inhibitor that is used for the treatment of peripheral vascular diseases. METHODS: We investigated the effect of CsA on collagen synthesis and clarified whether PTX has protective effects against CsA-induced arterial vasculopathy using calf pulmonary artery endothelial cells. This study was carried out using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, reverse transcription- polymerase chain reaction (RT-PCR), Western blot analysis, nitric oxide (NO) detection, and cyclic guanosine monophosphate (cGMP) enzyme immunoassay. RESULTS: CsA treatment significantly increased the expression of collagen type I mRNA and protein and decreased the production of NO and cGMP. However, pre-treatment with PTX exerted anticollagen effect by suppressing the CsA-induced formation of collagen, but this effect of PTX was not modulated by NO and cGMP. CONCLUSION: Based on the present results, it is expected that PTX may have a protective effect against CsA-induced arterial vasculopathy, although the mechanism of PTX needs to be clarified in future studies.
Autoimmune Diseases ; Blotting, Western ; Collagen ; Collagen Type I ; Cyclic GMP ; Cyclosporine ; Endothelial Cells ; Guanosine Monophosphate ; Immunoenzyme Techniques ; Nitric Oxide ; Pentoxifylline ; Peripheral Vascular Diseases ; Polymerase Chain Reaction ; Pulmonary Artery ; Rejection (Psychology) ; RNA, Messenger ; Tetrazolium Salts ; Thiazoles ; Transplants

PURPOSE: The overactive bladder (OAB) syndrome is characterized by urgency usually with frequency and nocturia. Tamsulosin, alpha1-adrenergic receptor antagonist, is widely used to reduce symptoms of urinary obstruction and prostatic hyperplasia. Tamsulosin can across the blood-brain barrier. We investigated the effects of tamsulosin on the symptoms of OAB in relation to neuronal activity using rats. METHODS: Adult female Sprague-Dawley rats, weighing 250+/-10 g (9 weeks old), were used in this study. The animals were divided into five groups (n=8 in each group): control group, OAB-induced group, OAB-induced and 0.01 mg/kg tamsulosin-treated group, OAB-induced and 0.1 mg/kg tamsulosin-treated group, and OAB-induced and 1 mg/kg tamsulosin-treated group. OAB was induced by intraperitoneal injection of cyclophosphamide (75 mg/kg) every third day for 10 days. The rats in the tamsulosin-treated groups orally received tamsulosin once a day for 14 consecutive days at the respective dose of the groups, starting 1 day after the induction of OAB. Cystometry for bladder pressure determination, immunohistochemistry for c-Fos, nicotinamide adenine dinucleotide phosphate-diaphorase histochemistry for nitric oxide synthase (NOS) in the neuronal voiding centers and western blot for inducible NOS in the bladder were conducted. RESULTS: Cyclophosphamide injection enhanced contraction pressure and time, representing the induction of OAB. Contraction pressure and time were significantly suppressed by tamsulosin treatment. c-Fos and NOS expressions in the neuronal voiding centers were enhanced by induction of OAB. OAB-induced c-Fos and NOS expressions were suppressed by tamsulosin treatment. CONCLUSIONS: Tamsulosin exerts inhibitory effect on neuronal activation in the neuronal voiding centers of OAB. The present results suggest the possibility that tamsulosin is effective therapeutic modality for ameliorating the symptoms of OAB.
Adult ; Animals ; Blood-Brain Barrier ; Blotting, Western ; Contracts ; Cyclophosphamide ; Female ; Humans ; Immunohistochemistry ; Injections, Intraperitoneal ; NAD ; Neurons ; Nitric Oxide Synthase ; Nocturia ; Prostatic Hyperplasia ; Rats ; Rats, Sprague-Dawley ; Sulfonamides ; Urinary Bladder ; Urinary Bladder, Overactive

The purpose of this study is to investigate the mechanism of alternative responses to low dose irradiation for neuronal cell proliferation in the dentate gyrus of rats. To determine the effect of a single exposure to radiation, rats were irradiated with a single dose of 0.1, 1, 10 or 20 Gy. To determine the effect of the cumulative dose, the animals were irradiated daily with 0.01 Gy or 0.1 Gy from 1 to 4 days. The neuronal cell proliferation was evaluated using immunohistochemistry for 5-bromo-2'-deoxyuridine (BrdU), Ki-67 and terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) staining. Four consecutive daily irradiations with a 0.01 Gy/fraction increased the number of BrdU-positive and Ki-67-positive cells in a dose dependent manner, but this did not affect the number of TUNEL-positive cells. However, there was not a dose dependent relationship for the 0.1 Gy/fraction irradiation with the number of BrdU, Ki-67 and TUNEL positive cells. Our data support the explanation that the adaptive response, induced by low-dose radiation, in the hippocampus of rats is more likely a reflection of the perturbations of cell cycle progression.
Rats, Sprague-Dawley ; Rats ; Radiation Dosage ; Neurons/*cytology/*radiation effects ; Neuronal Plasticity/*radiation effects ; Male ; Dose-Response Relationship, Radiation ; Dentate Gyrus/*cytology/*radiation effects ; Cell Survival/radiation effects ; Cell Proliferation/*drug effects ; Animals ; Adaptation, Physiological/radiation effects