The expression of caveolin-1 and -2 in the retina was examined; Western blot analysis showed that both were present. Immunohistochemistry indicated that caveolin-1 was expressed in the majority of retinal layers, including the ganglion cell layer, inner plexiform layer, outer plexiform layer, and in the vascular endothelial cells of the retina. Caveolin-2 was primarily immunostained in the vessels, but in a few other elements as well. This is the first demonstration of caveolin differential expression in the retina of rats, and suggests that caveolin plays an important role in signal transduction in glial cells and neuronal cells.
Animals ; Caveolin 1/*analysis/immunology ; Caveolin 2/*analysis/immunology ; Gene Expression Regulation ; Immunohistochemistry ; Male ; Rats ; Rats, Sprague-Dawley ; Retina/*chemistry

Melatonin (N-acetyl-5-methoxytryptamine), a pineal neurohormone, is a hydroxyl radical scavenger and antioxidant, and plays an important role in the immune system. We studied the effect of exogenous melatonin on the pathogenesis of experimental autoimmune encephalomyelitis (EAE). EAE was induced in Lewis rats by immunization with rat spinal cord homogenates. Subsequent oral administration of melatonin at 5 mg/kg significantly reduced the clinical severity of EAE paralysis compared with administration of the vehicle alone (p<0.01). Infiltration of ED1 macrophages and CD4 T cells into spinal cords occurred both in the absence and presence of melatonin treatment, but melatonin-treated rats had less spinal cord infiltration of inflammatory cells than did the control group. ICAM-1 immunoreactivity in the blood vessels of EAE lesions was decreased in melatonin-treated rats compared to vehicle-treated rats. These findings suggest that exogenous melatonin ameliorates EAE via a mechanism involving reduced expression of ICAM-1 and lymphocyte function associated antigen-1a in autoimmune target organs.
Animals ; Encephalomyelitis, Autoimmune, Experimental/*immunology/prevention & control ; Female ; Immunohistochemistry ; Intercellular Adhesion Molecule-1/analysis/*immunology ; Male ; Melatonin/administration & dosage/*physiology ; Rats ; Rats, Inbred Lew ; Spinal Cord/chemistry/pathology

Parkinson's disease is known to exhibit progressive degeneration of the dopaminergic neurons in the substantia nigra via inhibition of glutathione metabolism. It is well known that 6-Hydroxydopamine (6-OHDA) induces Parkinson's disease-like symptoms, while resveratrol (3,5,4'-trihydroxystilbene) has been shown to have anti-inflammatory and antioxidant effects. In the present study, we investigated the neuroprotective effects of resveratrol, a phytoalexin found in grapes and various plants, on 6-OHDA-induced cell damage to the SH-SY5Y human neuroblastoma cell line. Resveratrol (5 and 10 microM) inhibited 6-OHDA (60 microM)-induced cytotoxicity in SH-SY5Y cells and induced a reduction of the number of apoptotic nuclei caused by 6-OHDA treatment. Additionally, the total apoptotic rate of cells treated with both resveratrol (10 microM) and 6-OHDA (60 microM) was less than that of 6-OHDA treated cells. Resveratrol also dose-dependently (1, 5 and 10 microM) scavenged reactive oxygen species (ROS) induced by 6-OHDA in SH-SY5Y cells and prevented depletion of glutathione in response to the 6-OHDA-induced cytotoxicity in the glutathione assay. Overall, these results indicate that resveratrol exerts a neuroprotective effect against 6-OHDA-induced cytotoxicity of SH-SY5Y cells by scavenging ROS and preserving glutathione.
Antioxidants ; Apoptosis ; Cell Line* ; Dopaminergic Neurons ; Glutathione ; Humans ; Metabolism ; Neuroblastoma ; Neuroprotective Agents* ; Oxidopamine ; Parkinson Disease ; Reactive Oxygen Species ; Substantia Nigra ; Vitis

We administered local injections of botulinum A toxin to 15 patients wlth medically intratrable cervical dystonia Thirteen of the patients (87%) improved substantially (global effect >or=3 ; fiom -l = aggravated to +5 = markedly improved, fully functional, very happy with the results), with a mean total dose of 75.9 units. Of the 8 patients who reported pain, 7 (88%) had almost complete re!ief of pain. Only 6 of 15 (40%) patients had mild to moderate complications. More muscles had been injected in rotatocollis (mean, 5.2) than in laterocollis (mean, 3.0) (p<0.05). The global effects in rotatocollis (mean, 3.4) and laterocollis (mean, 3.3) were significantly better than anterocollis (mean, 1.5) (p<0.05). We conclude that botulinum A toxin is also effective in low doses when given in due consideration of the cervical muscle contraction patterns.
Botulinum Toxins, Type A* ; Humans ; Muscle Contraction ; Muscles ; Torticollis*

Parkinson's disease (PD) is an irreversible neurological disorder with related locomotor dysfunction and is haracterized by the selective loss of nigral neurons. PD can be experimentally induced by 6-hydroxydopamine (6-OHDA). It has been reported that reactive oxygen species, which deplete endogenous glutathione (GSH) levels, may play important roles in the dopaminergic cell death characteristic of PD. Fucoidan, a sulfated algal polysaccharide, exhibits anti-inflammatory and anti-oxidant actions. In this study, we investigated whether fucoidan can protect against 6-OHDA-mediated cytotoxicity in SH-SY5Y cells. Cytotoxicity was evaluated by using MTT and LDH assays. Fucoidan alleviated cell damage evoked by 6-OHDA dose-dependently. Fucoidan reduced the number of apoptotic nuclei and the extent of annexin-V-associated apoptosis, as revealed by DAPI staining and flow cytometry. Elevation of lipid peroxidation and caspase-3/7 activities induced by 6-OHDA was attenuated by fucoidan, which also protected against cytotoxicity evoked by buthionine-sulfoximine-mediated GSH depletion. Reduction in the glutathione/glutathione disulfide ratio induced by 6-OHDA was reversed by fucoidan, which also inhibited 6-OHDA-induced disruption of mitochondrial membrane potential. The results indicate that fucoidan may have protective action against 6-OHDA-mediated neurotoxicity by modulating oxidative injury and apoptosis through GSH depletion.
Apoptosis ; Cell Death ; Flow Cytometry ; Glutathione ; Lipid Peroxidation ; Membrane Potential, Mitochondrial ; Nervous System Diseases ; Neurons ; Oxidopamine ; Parkinson Disease ; Reactive Oxygen Species

To evaluate the current status of cerebrovascular disease in Korea, we performed a retrospective study on 1260 cases of stroke who had been admitted to or had visited Seoul National University Hospital, Choongnam National University Hospital, Hanyang University Hosipital, and Chung Ang University Hospital in the period from Jul 1, 1986 to Jun 30, 1987. The incidence was highest in sixth and seventh decades. Ischemic stroke (51.1%) was more common thar, hemorrhagic stroke (47.6%), and thrombotic infarction was the leading type (37.7%) of all kinds of strokes. Middle cerebral arterial territory was the most commonly involved site in thrombotic and embolic stroke. Among intracerebral hemorrhage, basal ganglia hemorrhage was found in 47.7%, and was followed by thalamic(23.8%), lobar (15.3%) and pontine hemorrhage (9.4%). Primary intraventricular hemorrhage (IVH) was relatively rare (8 cases, 7.5% of all IVH), and hemorrhages in basal ganglia or thalamus frequently induced secondary IVH. 16 cases (10.7%) of subarachnoid hamorrhage were accompanied by secondary IVH. This study suggests changing trends of stroke in Korea, and multicenter prospective study using stroke registry is requird for confirmation.
Basal Ganglia ; Basal Ganglia Hemorrhage ; Cerebral Hemorrhage ; Hemorrhage ; Incidence ; Infarction ; Korea* ; Retrospective Studies ; Seoul ; Stroke ; Thalamus

Recently, loss of endogenous glutathione during N-methyl-D-aspartate (NMDA) receptor-mediated excitotoxic injury, and the resultant overproduction of reactive oxygen species (ROS) through an arachidonic acid cascade process in brain, have been implicated in neuronal damage in various neurodegenerative diseases. Glutathione depletion induced by L-buthionine-(S,R)-sulfoximine (BSO), an inhibitor of glutathione synthesis, is known to cause arachidonic acid-mediated excitotoxicity in primary mixed cortical cultures. The aim of this study was to investigate whether esculetin (6,7-dihydroxycoumarin), an inhibitor of lipoxygenase, protects against neurotoxicity induced by NMDA or BSO. We observed that neurotoxicity induced by NMDA but not kainic acid was attenuated by esculetin. At the same concentration (100 microM), esculetin attenuated the 45Ca2+ uptake elevation induced by NMDA. Free radical-mediated neuronal injury induced by H2O2 and xanthine/xanthine oxidase was concentration-dependently blocked by esculetin. Esculetin (1-30 microM) dose-dependently inhibited BSO-induced neuronal injury. In addition, arachidonate-induced neurotoxicity was completely blocked by esculetin. BSO also reduced glutathione peroxidase (GPx) activity, but did not change glutathione reductase (GR) activity 24 h after treatment. Esculetin dose-dependently increased GR activity, but did not alter GPx activity. These findings suggest that esculetin can contribute to the rescue of neuronal cells from NMDA neurotoxicity and that this protective effect occurs partly through NMDA receptor modulation and the sparing of glutathione depletion.
Arachidonic Acid ; Brain ; Glutathione ; Glutathione Reductase ; Kainic Acid ; Lipoxygenase ; N-Methylaspartate ; Neurodegenerative Diseases ; Neurons ; Oxidoreductases ; Peroxidase ; Reactive Oxygen Species ; Umbelliferones

To elucidate the role of nitric oxide synthase (NOS) in the pathogenesis of experimental autoimmune encephalomyelitis (EAE), we analyzed the expression of constitutive neuronal NOS (nNOS), endothelial NOS (eNOS), and inducible NOS (iNOS) in the spinal cords of rats with EAE. We further examined the structural interaction between apoptotic cells and spinal cord cells including neurons and astrocytes, which are potent cell types of nitric oxide (NO) production in the brain. Western blot analysis showed that three forms of NOS significantly increased in the spinal cords of rats at the peak stage of EAE, while small amounts of these enzymes were identified in the spinal cords of rats without EAE. Immunohistochemical study showed that the expression of either nNOS or eNOS increased in the brain cells including neurons and astrocytes during the peak and recovery stages of EAE, while the expression of iNOS was found mainly in the inflammatory macrophages in the perivascular EAE lesions. Double labeling showed that apoptotic cells had intimate contacts with either neurons or astrocytes, which are major cell types to express nNOS and eNOS constitutively. Our results suggest that the three NOS may play an important role in the recovery of EAE.
Animals ; Apoptosis ; Encephalomyelitis, Autoimmune, Experimental/*enzymology ; Endothelium, Vascular/enzymology ; Immunohistochemistry ; In Situ Nick-End Labeling ; Male ; Nitric Oxide Synthase/*metabolism ; Nitric Oxide Synthase Type I ; Nitric Oxide Synthase Type II ; Nitric Oxide Synthase Type III ; Rats ; Rats, Inbred Lew ; Spinal Cord/*enzymology/pathology

Antioxidants ; Central Nervous System Diseases ; Central Nervous System ; Citrus ; Demyelinating Diseases ; Dietary Supplements ; Encephalomyelitis, Autoimmune, Experimental ; Flavonoids ; Hesperidin ; Hippocampus ; Neurodegenerative Diseases

Forty-one patients with hemifacial spasm received botulinum A toxin in total 73 visits. In 68 of 73 visits(93%), substantial improvement with peak effect(change in severity of hemifacial spasm 22 ) was obtained, with a mean total dose of 12.5 units. Mean severity of hemifacial spasm before and after treatrnent were 3.8 and 1.1 respectively on a 0-5 scale. Mean muscle dose of orbicularis oculi was 9.0 units There was a significant association between muscle dose and post-treatment weakness of orbicularis oculi(Spearman correlation coefficient, 0.42691). There was also a striking and significant association between post-treatment weakness of orbicularis oculi and peak effect(Spearman correlation coefficient, 0.74883). Lagophthalmos occurred only in 2 of 28 visits (7%) who received lesser than 10.0 units for orbicularis oculi as compard to 22% in the higher dose group. But peak effects showed no significant difference between the two groups(p =O.I30). We suggest that the occurrence of lagophthalmos can be reduced with the dose lesser than 10.0 units for orbicularis oculi, maintaining the significant effect.
Botulinum Toxins, Type A* ; Hemifacial Spasm* ; Humans ; Strikes, Employee