Satoshi Kashii | Aichi Shukutoku University (original) (raw)

Papers by Satoshi Kashii

Research paper thumbnail of Superoxide generated by the stimulation of NMDA receptors plays a key role in post–ischemic apoptosis in the inner retina

Investigative Ophthalmology & Visual Science, 2004

Research paper thumbnail of Role of Pkc on Mitochondrial K(atp) Channel-Mediated Neuro-Protection by Bradykinin

Research paper thumbnail of Role Of Mitochondrial K(atp) Channel And Pkc On The Neuro-protection Against Glutamate Neurotoxicity

Research paper thumbnail of Visual Motion Perception in Human V5 of Glaucoma Patients Demonstrated by Magnetoencephalography

Investigative Ophthalmology & Visual Science, 2003

Research paper thumbnail of Protective effect of FK506 on glutamate-induced neurotoxicity in cultured retinal neurone

Japanese Journal of Pharmacology, 1997

Research paper thumbnail of Release of glutamate and neuronal degeneration induced by ischemia in the retina

Japanese Journal of Pharmacology, 1995

Research paper thumbnail of Protective action of dopamine against glutamate neurotoxicity in the retina

Investigative ophthalmology & visual science, 1994

The electrophysiologic study using patch-clamp techniques demonstrated that NMDA-induced currents... more The electrophysiologic study using patch-clamp techniques demonstrated that NMDA-induced currents had properties similar to those recorded in the brain. Primary cultures obtained from the fetal rat retina (gestation days 16 to 19) were used for the experiment. Immunocytochemical and electrophysiologic studies were done to identify the cultured cells. The neurotoxic effects of glutamate or N-methyl-D-aspartate (NMDA) on the retinal cultures were quantitatively assessed using the trypan blue exclusion method. The immunocytochemical study revealed that the major component of the rat retinal cultures was neurons including amacrine cells. The electrophysiologic study using patch-clamp techniques demonstrated that exposure to NMDA-induced currents with properties characteristic of those recorded in the brain. Brief exposure of these neurons to glutamate or NMDA induced delayed cell death. Glutamate neurotoxicity was prevented by the application of dopamine and forskolin. The protective ac...

Research paper thumbnail of Retinal Neurotoxicity of Nitric Oxide Donors With Different Half-Life of Nitric Oxide Release: Involvement of N-Methyl-D-aspartate Receptor

Journal of Pharmacological Sciences, 2003

We compared the degree of neurotoxic outcome in the retina exposed to three nitric oxide (NO) don... more We compared the degree of neurotoxic outcome in the retina exposed to three nitric oxide (NO) donors with different half-life of NO release. Intravitreal injection of NO donors resulted in a significant decrease in cell density in the ganglion cell layer and thinning of the inner plexiform layer in a half-life time-dependent manner. Concurrent injection of an NOtrapping reagent with an NO donor abolished NO donor-induced retinal damage. (+)-MK-801 also prevented NO-induced retinal damage, indicating that N-methyl-D-aspartate receptors are partly involved in NO-induced neurodegeneration. These results may be relevant to a pathogenic role of NO-glutamate receptor in several ophthalmic disorders.

Research paper thumbnail of Blockade of Retinal NMDA Receptors by Sodium Nitroprusside Is Probably Due to Nitric Oxide Formation

Japanese Journal of Pharmacology, 1993

Effects of a nitric oxide (NO)-producing agent, sodium nitroprusside, on N-methyl-D-aspar tate (N... more Effects of a nitric oxide (NO)-producing agent, sodium nitroprusside, on N-methyl-D-aspar tate (NMDA) receptor activation in the cultured retinal neurons of rats were examined. NMDA in a Mg2+ free medium evoked inward currents at the resting membrane potential. Inward currents were also evoked by kainate. Sodium nitroprusside markedly reduced the NMDA-induced currents without affecting those in duced by kainate. These results suggest the possible existence of a negative feed back system of NO which serves to regulate the activation of NMDA receptors in retinal neurons.

Research paper thumbnail of Retinal Neuronal Death Induced by Intraocular Administration of a Nitric Oxide Donor and Its Rescue by Neurotrophic Factors in Rats

Investigative Opthalmology & Visual Science, 2003

PURPOSE. To investigate the neurotoxic outcome in the rat retina exposed to nitric oxide (NO) rel... more PURPOSE. To investigate the neurotoxic outcome in the rat retina exposed to nitric oxide (NO) released from an NO donor and to evaluate the effects of neurotrophic factors on the survival of NO-damaged retinal cells. METHODS. An NO releasing compound, N-ethyl-2-(1-ethyl-2-hydroxy-2-nitrosohydrazino) ethanamine (NOC 12), was intravitreously injected into a rat's right eye. The influences of NOC 12 on retinal neurons and the neuroprotective effects of ciliary neurotrophic factor (CNTF) or brain-derived neurotrophic factor (BDNF) on NOC 12-mediated damage were estimated by counting cells in the ganglion cell layer (GCL) and by measuring the thickness of retinal layers. The exact count of retinal ganglion cells (RGCs) was also confirmed by means of retrograde labeling with a fluorescent tracer. RESULTS. Morphometric analyses of retinal damage in the NOC 12-exposed eyes demonstrated a significant and dose-dependent decrease in cell density in the GCL and a reduction in thickness of the inner plexiform layer and inner nuclear layer, but not of the outer nuclear layer. TdT-dUTP terminal nick-end labeling of retinal sections after intravitreous injection of NOC 12 demonstrated that NO could trigger apoptotic cell death. The counting of the RGCs labeled with a fluorescent tracer suggested that a decrease in GCL cell density induced by NOC 12 reflects a loss in RGCs. Treatment with CNTF (1 g) or BDNF (1 g) before the intravitreous injection of NOC 12 (400 nmol) demonstrated that these trophic factors have protective effects against NO-induced neuronal cell death in the retina. CONCLUSIONS. Exogenous NO induces retinal neurotoxicity, suggesting that NO plays a pathogenic role in degenerative retinal diseases. BDNF and CNTF protect retinal neurons from NOmediated neurotoxicity.

Research paper thumbnail of Superior oblique paresis with contralateral relative afferent pupillary defect

Graefe's Archive for Clinical and Experimental Ophthalmology, 2000

The purpose of this study is to report a case of superior oblique paresis and contralateral relat... more The purpose of this study is to report a case of superior oblique paresis and contralateral relative afferent pupillary defect (RAPD) with normal vision in a patient with brainstem astrocytoma. We correlated the patient's clinical findings with anatomical substrates on magnetic resonance imaging (MRI) findings. The patient had right-sided superior oblique paresis. There was a left-sided RAPD, although visual acuities and visual fields were normal in both eyes. T1-weighted, gadolinium-enhanced MRI demonstrated a hyperintense area in the right dorsal midbrain. It is suggested that the lesion damaged both the pretectal afferent pupillary pathway and fascicles of the trochlear nerve, causing a unique combination of neuro-ophthalmologic findings.

Research paper thumbnail of Protective effects of ifenprodil against glutamate-induced neurotoxicity in cultured retinal neurons

Graefe's Archive for Clinical and Experimental Ophthalmology, 2000

Research paper thumbnail of Temporal profile of visual evoked responses to pattern-reversal stimulation analyzed with a whole-head magnetometer

Experimental Brain Research, 1999

Research paper thumbnail of Inhibition of NMDA receptors and nitric oxide synthase reduces ischemic injury of the retina

European Journal of Pharmacology, 1998

This study was performed to examine the roles of body temperature, NMDA receptors and nitric oxid... more This study was performed to examine the roles of body temperature, NMDA receptors and nitric oxide NO synthase in post-ischemic retinal injury in rats. Cell loss in the ganglion cell layer and thinning of the inner plexiform layer were observed 7 days after ischemia. Cell loss in the ganglion cell layer but not thinning of the inner plexiform layer was reduced by hypothermia during ischemia. Intravenous Ž. v Ž. injection of dizocilpine MK-801 or N-nitro-L-arginine methyl ester L-NAME prior to ischemia ameliorated retinal injury. These results suggest that activation of NO synthase following NMDA receptor stimulation is involved in ischemia-induced retinal injury.

Research paper thumbnail of Protective effects of selegiline and desmethylselegiline against N-methyl-d-aspartate-induced rat retinal damage

European Journal of Pharmacology, 2003

Selegiline, a therapeutic agent of Parkinson&... more Selegiline, a therapeutic agent of Parkinson's disease, and its metabolite, desmethylselegiline, were explored for their neuroprotective effects against N-methyl-D-aspartate (NMDA)-induced cell death in rat retina. Morphometric analysis of the retina revealed that an intravitreal injection of NMDA induced a significant decrease in cell density in the ganglion cell layer and in thickness of the inner plexiform layer, but not of other retinal layers such as the outer nuclear layer. Concurrent intravitreal injection of selegiline with NMDA did not show a significant protective effect, whereas co-injection of desmethylselegiline provided protection from NMDA-induced retinal damage. Parenteral administration (both single and consecutive dosing) of selegiline significantly prevented loss of ganglion cell layer cells. Counting of retinal ganglion cells by fluorescent tracer labeling confirmed that selegiline protected retinal ganglion cells from NMDA toxicity. The selegiline treatment did not produce a significant increase, though it tended to such as effect, in a brain-derived neurotrophic factor (BDNF) level in the retina, when compared with the NMDA-treated control group. These results indicate that parenteral treatment with selegiline rescues inner retinal cells from NMDA-induced neural damage, and that desmethylselegiline may contribute, in part, to the protective activities of selegiline. The neuroprotective effects exerted by selegiline may be attributed partially to a change in the retinal BDNF expression.

Research paper thumbnail of Apoptotic DNA fragmentation and upregulation of Bax induced by transient ischemia of the rat retina

Brain Research, 1999

Apoptotic DNA fragmentation and upregulation of bcz induced by transient ischemia of the rat retina

Research paper thumbnail of Vitamin B6 protects primate retinal neurons from ischemic injury

Research paper thumbnail of Dual actions of nitric oxide inN-methyl-d-aspartate receptor-mediated neurotoxicity in cultured retinal neurons

Brain Research, 1996

This study was performed to elucidate the role of nitric oxide (NO) in N-methyl-D-aspartate (NMDA... more 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-rain 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, N'°-nitro-L-arginine (300 /xM), with glutamate or NMDA reduced cell death by 70%. A brief exposure of the cells to sodium nitroprusside (SNP, 500 /xM) or S-nitrosocysteine (SNOC, 500/xM), 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 p~M SNOC alone had no effect on the cell viability. However, pretreatment with 50 /zM SNOC as well as simultaneous application of 50 /zM 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.

Research paper thumbnail of Evaluation of retinal ganglion cell death using explant cultures

Japanese Journal of Pharmacology

Research paper thumbnail of A protective effect of nicotine against glutamate neurotoxicity in cultured rat retinal neurons

Neuroscience Research

ABSTRACT

Research paper thumbnail of Superoxide generated by the stimulation of NMDA receptors plays a key role in post–ischemic apoptosis in the inner retina

Investigative Ophthalmology & Visual Science, 2004

Research paper thumbnail of Role of Pkc on Mitochondrial K(atp) Channel-Mediated Neuro-Protection by Bradykinin

Research paper thumbnail of Role Of Mitochondrial K(atp) Channel And Pkc On The Neuro-protection Against Glutamate Neurotoxicity

Research paper thumbnail of Visual Motion Perception in Human V5 of Glaucoma Patients Demonstrated by Magnetoencephalography

Investigative Ophthalmology & Visual Science, 2003

Research paper thumbnail of Protective effect of FK506 on glutamate-induced neurotoxicity in cultured retinal neurone

Japanese Journal of Pharmacology, 1997

Research paper thumbnail of Release of glutamate and neuronal degeneration induced by ischemia in the retina

Japanese Journal of Pharmacology, 1995

Research paper thumbnail of Protective action of dopamine against glutamate neurotoxicity in the retina

Investigative ophthalmology & visual science, 1994

The electrophysiologic study using patch-clamp techniques demonstrated that NMDA-induced currents... more The electrophysiologic study using patch-clamp techniques demonstrated that NMDA-induced currents had properties similar to those recorded in the brain. Primary cultures obtained from the fetal rat retina (gestation days 16 to 19) were used for the experiment. Immunocytochemical and electrophysiologic studies were done to identify the cultured cells. The neurotoxic effects of glutamate or N-methyl-D-aspartate (NMDA) on the retinal cultures were quantitatively assessed using the trypan blue exclusion method. The immunocytochemical study revealed that the major component of the rat retinal cultures was neurons including amacrine cells. The electrophysiologic study using patch-clamp techniques demonstrated that exposure to NMDA-induced currents with properties characteristic of those recorded in the brain. Brief exposure of these neurons to glutamate or NMDA induced delayed cell death. Glutamate neurotoxicity was prevented by the application of dopamine and forskolin. The protective ac...

Research paper thumbnail of Retinal Neurotoxicity of Nitric Oxide Donors With Different Half-Life of Nitric Oxide Release: Involvement of N-Methyl-D-aspartate Receptor

Journal of Pharmacological Sciences, 2003

We compared the degree of neurotoxic outcome in the retina exposed to three nitric oxide (NO) don... more We compared the degree of neurotoxic outcome in the retina exposed to three nitric oxide (NO) donors with different half-life of NO release. Intravitreal injection of NO donors resulted in a significant decrease in cell density in the ganglion cell layer and thinning of the inner plexiform layer in a half-life time-dependent manner. Concurrent injection of an NOtrapping reagent with an NO donor abolished NO donor-induced retinal damage. (+)-MK-801 also prevented NO-induced retinal damage, indicating that N-methyl-D-aspartate receptors are partly involved in NO-induced neurodegeneration. These results may be relevant to a pathogenic role of NO-glutamate receptor in several ophthalmic disorders.

Research paper thumbnail of Blockade of Retinal NMDA Receptors by Sodium Nitroprusside Is Probably Due to Nitric Oxide Formation

Japanese Journal of Pharmacology, 1993

Effects of a nitric oxide (NO)-producing agent, sodium nitroprusside, on N-methyl-D-aspar tate (N... more Effects of a nitric oxide (NO)-producing agent, sodium nitroprusside, on N-methyl-D-aspar tate (NMDA) receptor activation in the cultured retinal neurons of rats were examined. NMDA in a Mg2+ free medium evoked inward currents at the resting membrane potential. Inward currents were also evoked by kainate. Sodium nitroprusside markedly reduced the NMDA-induced currents without affecting those in duced by kainate. These results suggest the possible existence of a negative feed back system of NO which serves to regulate the activation of NMDA receptors in retinal neurons.

Research paper thumbnail of Retinal Neuronal Death Induced by Intraocular Administration of a Nitric Oxide Donor and Its Rescue by Neurotrophic Factors in Rats

Investigative Opthalmology & Visual Science, 2003

PURPOSE. To investigate the neurotoxic outcome in the rat retina exposed to nitric oxide (NO) rel... more PURPOSE. To investigate the neurotoxic outcome in the rat retina exposed to nitric oxide (NO) released from an NO donor and to evaluate the effects of neurotrophic factors on the survival of NO-damaged retinal cells. METHODS. An NO releasing compound, N-ethyl-2-(1-ethyl-2-hydroxy-2-nitrosohydrazino) ethanamine (NOC 12), was intravitreously injected into a rat's right eye. The influences of NOC 12 on retinal neurons and the neuroprotective effects of ciliary neurotrophic factor (CNTF) or brain-derived neurotrophic factor (BDNF) on NOC 12-mediated damage were estimated by counting cells in the ganglion cell layer (GCL) and by measuring the thickness of retinal layers. The exact count of retinal ganglion cells (RGCs) was also confirmed by means of retrograde labeling with a fluorescent tracer. RESULTS. Morphometric analyses of retinal damage in the NOC 12-exposed eyes demonstrated a significant and dose-dependent decrease in cell density in the GCL and a reduction in thickness of the inner plexiform layer and inner nuclear layer, but not of the outer nuclear layer. TdT-dUTP terminal nick-end labeling of retinal sections after intravitreous injection of NOC 12 demonstrated that NO could trigger apoptotic cell death. The counting of the RGCs labeled with a fluorescent tracer suggested that a decrease in GCL cell density induced by NOC 12 reflects a loss in RGCs. Treatment with CNTF (1 g) or BDNF (1 g) before the intravitreous injection of NOC 12 (400 nmol) demonstrated that these trophic factors have protective effects against NO-induced neuronal cell death in the retina. CONCLUSIONS. Exogenous NO induces retinal neurotoxicity, suggesting that NO plays a pathogenic role in degenerative retinal diseases. BDNF and CNTF protect retinal neurons from NOmediated neurotoxicity.

Research paper thumbnail of Superior oblique paresis with contralateral relative afferent pupillary defect

Graefe's Archive for Clinical and Experimental Ophthalmology, 2000

The purpose of this study is to report a case of superior oblique paresis and contralateral relat... more The purpose of this study is to report a case of superior oblique paresis and contralateral relative afferent pupillary defect (RAPD) with normal vision in a patient with brainstem astrocytoma. We correlated the patient's clinical findings with anatomical substrates on magnetic resonance imaging (MRI) findings. The patient had right-sided superior oblique paresis. There was a left-sided RAPD, although visual acuities and visual fields were normal in both eyes. T1-weighted, gadolinium-enhanced MRI demonstrated a hyperintense area in the right dorsal midbrain. It is suggested that the lesion damaged both the pretectal afferent pupillary pathway and fascicles of the trochlear nerve, causing a unique combination of neuro-ophthalmologic findings.

Research paper thumbnail of Protective effects of ifenprodil against glutamate-induced neurotoxicity in cultured retinal neurons

Graefe's Archive for Clinical and Experimental Ophthalmology, 2000

Research paper thumbnail of Temporal profile of visual evoked responses to pattern-reversal stimulation analyzed with a whole-head magnetometer

Experimental Brain Research, 1999

Research paper thumbnail of Inhibition of NMDA receptors and nitric oxide synthase reduces ischemic injury of the retina

European Journal of Pharmacology, 1998

This study was performed to examine the roles of body temperature, NMDA receptors and nitric oxid... more This study was performed to examine the roles of body temperature, NMDA receptors and nitric oxide NO synthase in post-ischemic retinal injury in rats. Cell loss in the ganglion cell layer and thinning of the inner plexiform layer were observed 7 days after ischemia. Cell loss in the ganglion cell layer but not thinning of the inner plexiform layer was reduced by hypothermia during ischemia. Intravenous Ž. v Ž. injection of dizocilpine MK-801 or N-nitro-L-arginine methyl ester L-NAME prior to ischemia ameliorated retinal injury. These results suggest that activation of NO synthase following NMDA receptor stimulation is involved in ischemia-induced retinal injury.

Research paper thumbnail of Protective effects of selegiline and desmethylselegiline against N-methyl-d-aspartate-induced rat retinal damage

European Journal of Pharmacology, 2003

Selegiline, a therapeutic agent of Parkinson&... more Selegiline, a therapeutic agent of Parkinson's disease, and its metabolite, desmethylselegiline, were explored for their neuroprotective effects against N-methyl-D-aspartate (NMDA)-induced cell death in rat retina. Morphometric analysis of the retina revealed that an intravitreal injection of NMDA induced a significant decrease in cell density in the ganglion cell layer and in thickness of the inner plexiform layer, but not of other retinal layers such as the outer nuclear layer. Concurrent intravitreal injection of selegiline with NMDA did not show a significant protective effect, whereas co-injection of desmethylselegiline provided protection from NMDA-induced retinal damage. Parenteral administration (both single and consecutive dosing) of selegiline significantly prevented loss of ganglion cell layer cells. Counting of retinal ganglion cells by fluorescent tracer labeling confirmed that selegiline protected retinal ganglion cells from NMDA toxicity. The selegiline treatment did not produce a significant increase, though it tended to such as effect, in a brain-derived neurotrophic factor (BDNF) level in the retina, when compared with the NMDA-treated control group. These results indicate that parenteral treatment with selegiline rescues inner retinal cells from NMDA-induced neural damage, and that desmethylselegiline may contribute, in part, to the protective activities of selegiline. The neuroprotective effects exerted by selegiline may be attributed partially to a change in the retinal BDNF expression.

Research paper thumbnail of Apoptotic DNA fragmentation and upregulation of Bax induced by transient ischemia of the rat retina

Brain Research, 1999

Apoptotic DNA fragmentation and upregulation of bcz induced by transient ischemia of the rat retina

Research paper thumbnail of Vitamin B6 protects primate retinal neurons from ischemic injury

Research paper thumbnail of Dual actions of nitric oxide inN-methyl-d-aspartate receptor-mediated neurotoxicity in cultured retinal neurons

Brain Research, 1996

This study was performed to elucidate the role of nitric oxide (NO) in N-methyl-D-aspartate (NMDA... more 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-rain 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, N'°-nitro-L-arginine (300 /xM), with glutamate or NMDA reduced cell death by 70%. A brief exposure of the cells to sodium nitroprusside (SNP, 500 /xM) or S-nitrosocysteine (SNOC, 500/xM), 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 p~M SNOC alone had no effect on the cell viability. However, pretreatment with 50 /zM SNOC as well as simultaneous application of 50 /zM 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.

Research paper thumbnail of Evaluation of retinal ganglion cell death using explant cultures

Japanese Journal of Pharmacology

Research paper thumbnail of A protective effect of nicotine against glutamate neurotoxicity in cultured rat retinal neurons

Neuroscience Research

ABSTRACT