K Kaneda

Publications (9)22.02 Total impact

• Article: Protective effects of ifenprodil against glutamate-induced neurotoxicity in cultured retinal neurons.

  S Zhang, S Kashii, H Yasuyoshi, M Kikuchi, Y Honda, K Kaneda, S Sato, A Akaike
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  ABSTRACT: To examine the effects of ifenprodil on glutamate-induced neurotoxicity in cultured retinal neurons. Primary cultures obtained from the fetal rat retina (gestation day 17-19) were used for the experiment. Neurotoxicity effects on retinal cultures were quantitatively assessed by the trypan blue exclusion method. The cells were exposed briefly (10 min) to excitatory amino acids (EAA, 1 mM) and then were incubated for 1 h in an EAA-free medium. Ifenprodil (10 mM) was added for the 10-min exposure to EAA and the subsequent 60-min incubation in an EAA-free medium. Ifenprodil dose-dependently prevented cell death induced by glutamate or NMDA, but did not affect that induced by kainate. The protective effects of ifenprodil against glutamate neurotoxicity were significantly reduced by spermidine, a polyamine modulatory site agonist, but not by glycine, a strychnine-insensitive glycine site agonist. The findings suggest that ifenprodil protected the cultured retinal cells we used in this study against glutamate neurotoxicity by its inhibitory action on the polyamine modulatory site of the NMDA receptor.
  Albrecht von Graæes Archiv für Ophthalmologie 11/2000; 238(10):846-52. · 2.17 Impact Factor
• Article: Apoptotic DNA fragmentation and upregulation of Bax induced by transient ischemia of the rat retina.

  K Kaneda, S Kashii, T Kurosawa, S Kaneko, A Akaike, Y Honda, M Minami, M Satoh
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  ABSTRACT: This study was performed to examine the involvement of apoptosis and the expression of bcl-2 family genes in ischemia-induced retinal injury. Retinal ischemia was induced in adult rats by raising the intraocular pressure to 130 mmHg for 45 min. Selective damage to the inner retina was observed 7 days after ischemia. No terminal deoxynucleotidyl-transferase (TdT)-mediated dUTP nick end-labeling (TUNEL) positive cells were observed in the normal retina, but there was a significant number of TUNEL positive cells 6-48 h after transient ischemia followed by a decrease at 96 and 168 h. The number of TUNEL positive cells reached a maximum at 24 h after ischemia. DNA laddering was observed on agarose gel electrophoresis with the retinas 24 and 48 h after ischemia but not in the normal retina. Semiquantitative reverse transcription-polymerase chain reaction (RT-PCR) revealed that bax gene expression did not change immediately after cessation of ischemia, but gradually increased as early as 6 h, reached a peak at 24 h, then decreased to near baseline levels at 168 h. On the other hand, bcl-2 gene expression showed no obvious changes at any time after transient ischemia. Moreover, intense Bax protein immunoreactivity was detected in the retinal sections at 24 h after ischemia although little immunoreactivity was present in the normal sections. These results suggest that apoptosis associated with the expression of Bax is involved in retinal cell loss after ischemic insult.
  Brain Research 02/1999; 815(1):11-20. · 2.73 Impact Factor
• Article: Mechanism of the pathogenesis of glutamate neurotoxicity in retinal ischemia.

  K Adachi, S Kashii, H Masai, M Ueda, C Morizane, K Kaneda, T Kume, A Akaike, Y Honda
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  ABSTRACT: This study was carried out to examine the involvement of glutamate and nitric oxide neurotoxicity in ischemia/reperfusion-induced retinal injury in vivo. We monitored glutamate release from in vivo cat retina during and after pressure-induced ischemia using a microdialysis technique. Morphometric studies were performed to study the effects of MK-801 (dizocilpine), L-NAME (N omega-nitro-L-arginine methyl ester), and D-NAME (N omega-nitro-D-arginine methyl ester) on the histological changes in the rat retina induced by ischemia or intravitreal injection of NMDA (N-methyl-D-aspartate; 200 nmol). A large release of glutamate occurred during ischemia, followed by a marked release after reperfusion. Histological changes occurred selectively in the inner part of the retina after ischemia as well as intravitreal injection of NMDA. Pretreatment with intravenous injection of MK-801 or L-NAME significantly inhibited the ischemic injury of the inner retina. Intravitreal injection of L-NAME inhibited NMDA-induced neurotoxicity in the retina. These findings indicate that nitric oxide mediates neurotoxic actions of glutamate which are responsible for ischemic injury in the retina.
  Albrecht von Graæes Archiv für Ophthalmologie 11/1998; 236(10):766-74. · 2.17 Impact Factor
• Source

  Available from: Michiko Mandai

  Article: Protective effects of FK506 against glutamate-induced neurotoxicity in retinal cell culture.

  M Kikuchi, S Kashii, M Mandai, H Yasuyoshi, Y Honda, K Kaneda, A Akaike
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  ABSTRACT: To examine the effects of FK506 on glutamate neurotoxicity in cultured retinal neurons. Experiments were performed with primary retinal cultures obtained from 17- to 19-day-old rat fetuses. To assess the effects of FK506 and other drugs on glutamate neurotoxicity, cultures were treated with a drug beginning 10 minutes before application of glutamate and continuing during the subsequent 10 minutes of glutamate exposure. The treated cells were then incubated for 1 hour in a drug-free and glutamate-free medium. After a 1-hour incubation, cell viability was quantitatively measured by the trypan blue exclusion method. Brief exposure to glutamate markedly decreased cell viability. FK506 protected against glutamate neurotoxicity in a dose-dependent manner. Rapamycin is a competitive inhibitor of FK506 that binds FK506 binding protein. Simultaneous application of rapamycin and FK506 negated the protective effects of FK506. Cyclosporin A, which binds and inhibits calcineurin, mimicked the protective effects of FK506. Treatment with FK506 did not affect the intracellular maximum Ca2+ concentration induced by glutamate application. Although FK506 exhibited protective action against Ca2+ ionophore-induced neurotoxicity, it had no effect on nitric oxide-induced neurotoxicity. Treatment with FK506 reduced the activity of nitric oxide synthase (NOS). FK506 protected against glutamate neurotoxicity by inhibiting NOS activity in cultured retinal neurons.
  Investigative Ophthalmology &amp Visual Science 07/1998; 39(7):1227-32. · 3.60 Impact Factor
• Article: [Techniques for evaluating neuronal death of the retina in vitro and in vivo].

  A Akaike, K Adachi, K Kaneda
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  ABSTRACT: This review describes the techniques to evaluate retinal neurodegeneration induced by excitatory amino acids and transient ischemia. Glutamate-induced neurotoxicity was examined in cultured rat cortical cells. Cultures obtained from the retinas of fetal rats were incubated in Eagle's minimal essential medium supplemented with 10% fetal calf serum or 10% horse serum at 37 degrees C in a humidified 5% CO2 atmosphere for 10-14 days. The neurotoxicity induced by glutamate was quantified by trypan blue exclusion. The viability of cultures was markedly reduced by a 10-min exposure to glutamate followed by incubation with glutamate-free medium for 1 hr. N-methyl-D-aspartate (NMDA)-induced retinal damage was examined in adult rats. Transverse sections of the retinas through the optic disk were stained with hematoxylin and eosin. A single intravitreal injection of NMDA damaged the ganglion cell layer and the inner plexiform layer without affecting the other retinal layers 7 days after injection. Retinal ischemia was induced by elevating the intraocular pressure for 45 min through the needle which was placed in the anterior chamber. Ischemia-induced retinal damage was inhibited by MK-801. These results indicate that the techniques described in this review can be employed to develop new drugs possessing neuroprotective action against neurodegeneration that occurs during retinal ischemia.
  Folia Pharmacologica Japonica 03/1998; 111(2):97-104.
• Article: Effect of SA4503, a novel sigma1 receptor agonist, against glutamate neurotoxicity in cultured rat retinal neurons.

  T Senda, S Mita, K Kaneda, M Kikuchi, A Akaike
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  ABSTRACT: We examined the effects of sigma1 receptor agonists against glutamate-induced neurotoxicity in cultured retinal neurons. Primary cultures obtained from fetal rat retinas (16-19 d gestation) were used. The neurotoxic effect of glutamate was quantitatively assessed using the trypan blue exclusion method. A brief exposure of retinal cultures to glutamate (500 microM) led to delayed neuronal cell death. The glutamate-induced neurotoxicity was inhibited by (5R,10S)-(+)-5-methyl-10,11-dihydro-5H-dibenzo-[a,b]-cyclohepten-5 ,10-imine hydrogen maleate (MK-801). The sigma1 receptor agonists, 1-(3,4-dimethoxyphenethyl)-4-(3-phenylpropyl)-piperazine dihydrochloride (SA4503) and (+)-pentazocine at a concentration range of 0.1 approximately 100 microM reduced the glutamate-induced neurotoxicity in a dose-dependent manner. In addition, the neuroprotective effects of both SA4503 and (+)-pentazocine were antagonized by co-treatment with N,N-dipropyl-2-[4-methoxy-3-(2-phenylethoxy)phenyl]ethylamine monohydrochloride (NE-100), a putative sigma1 receptor antagonist. These findings suggest that sigma1 receptor agonists protect retinal cells against glutamate-induced neurotoxicity.
  European Journal of Pharmacology 01/1998; 342(1):105-11. · 2.52 Impact Factor
• Source

  Available from: iovs.org

  Article: Protective effects of methylcobalamin, a vitamin B12 analog, against glutamate-induced neurotoxicity in retinal cell culture.

  M Kikuchi, S Kashii, Y Honda, Y Tamura, K Kaneda, A Akaike
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  ABSTRACT: To examine the effects of methylcobalamin on glutamate-induced neurotoxicity in the cultured retinal neurons. Primary cultures obtained from the fetal rat retina (gestation days 16 to 19) were used for the experiment. The neurotoxicity was assessed quantitatively using the trypan blue exclusion method. Glutamate neurotoxicity was prevented by chronic exposure to methylcobalamin and S-adenosylmethionine (SAM), which is formed in the metabolic pathway of methylcobalamin. Chronic exposure to methylcobalamin and SAM also inhibited the neurotoxicity induced by sodium nitroprusside that release nitric oxide. By contrast, acute exposure to methylcobalamin did not protect retinal neurons against glutamate neurotoxicity. Chronic administration of methylcobalamin protects cultured retinal neurons against N-methyl-D-aspartate-receptor-mediated glutamate neurotoxicity, probably by altering the membrane properties through SAM-mediated methylation.
  Investigative Ophthalmology &amp Visual Science 05/1997; 38(5):848-54. · 3.60 Impact Factor
• Article: Effects of B vitamins on glutamate-induced neurotoxicity in retinal cultures.

  K Kaneda, M Kikuchi, S Kashii, Y Honda, T Maeda, S Kaneko, A Akaike
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  ABSTRACT: The effects of B vitamins on glutamate-induced neurotoxicity were examined using primary cultures obtained from the rat retina. Cell viability was markedly reduced by a brief exposure to glutamate followed by incubation with glutamate-free media for 1 h. Glutamate cytotoxicity was reduced in the cultures that had been maintained in thiamine-, pyridoxine- or nicotinamide-containing medium before the exposure to glutamate. Glutamate cytotoxicity was also reduced by chronic application of thiamine pyrophosphate and pyridoxal phosphate, which are active coenzyme forms of thiamine and pyridoxine, respectively. By contrast, chronic application of riboflavin, pantothenate, biotin, folic acid and inositol did not affect glutamate cytotoxicity. None of the B vitamins tested had any effect on glutamate cytotoxicity when added only during the exposure to glutamate. These findings suggest that chronically applied thiamine, pyridoxine and nicotinamide protect retinal neurons against glutamate cytotoxicity.
  European Journal of Pharmacology 04/1997; 322(2-3):259-64. · 2.52 Impact Factor
• Article: Dual actions of nitric oxide in N-methyl-D-aspartate receptor-mediated neurotoxicity in cultured retinal neurons.

  S Kashii, M Mandai, M Kikuchi, Y Honda, Y Tamura, K Kaneda, A Akaike
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  ABSTRACT: This study was performed to elucidate the role of nitric oxide (NO) in N-methyl-D-aspartate (NMDA) receptor-mediated glutamate neurotoxicity in the retina. The experiments were done with primary retinal cultures obtained from 17- to 19-day-old rat fetuses. The NOS activity measured by monitoring the conversion of [3H]arginine to [3H]citrulline was approximately 5 pmol/min/mg protein. A 10-min exposure of the cultured cells to glutamate (1 mM) or NMDA (1 mM) followed by a 1-h incubation in a normal medium consistently resulted in 60% cell death. The concomitant addition of an inhibitor of NOS, Nomega-nitro-L-arginine (300 microM), with glutamate or NMDA reduced cell death by 70%. A brief exposure of the cells to sodium nitroprusside (SNP, 500 microM) or S-nitrosocysteine (SNOC, 500 microM), NO-generating agents, caused 60% cell death. Depletion of NO by reduced hemoglobin prevented the cell death induced by either glutamate, NMDA, or NO generating agents. Fifty microM SNOC alone had no effect on the cell viability. However, pretreatment with 50 microM SNOC as well as simultaneous application of 50 microM SNOC with NMDA inhibited cell death induced by NMDA. These findings indicate that a low concentration of NO plays a protective role in glutamate neurotoxicity via closing the NMDA receptor gated ion channel. However, elevated concentrations of NO, interacting with oxygen radicals, become toxic and mediate glutamate-induced neurotoxicity in the cultured retinal neurons.
  Brain Research 04/1996; 711(1-2):93-101. · 2.73 Impact Factor