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Biomedical subjects

M Sasa

Publications and source records attributed to M Sasa.

At least 37 records · Page 2Linked to original sources
PubMed2000

Involvement of NMDA-receptor in kainate-induced neurotoxicity in cultured fetal retinal neurons.

BACKGROUND: Both in vivo and in vitro studies suggest that excess stimulation of non-NMDA receptors can result in massive neuronal death in the retina. In particular, murine amacrine neurons have been known to show marked susceptibility to the toxic effects of kainate. PURPOSE: This study was designed to examine and characterize the role of N-methyl-D-aspartate (NMDA) receptor vs non-NMDA receptor in glutamate-induced neurotoxicity in the retina. METHODS: Primary cultures obtained from fetal rat retina (gestation day 16-19) were used for the experiment. The neurotoxicity was assessed quantitatively using the trypan blue exclusion method. Electrophysiological studies using patch-clamp techniques were performed to record whole-cell currents evoked by these excitatory amino acids. RESULTS: Removal of extracellular Ca2+ from the medium or application of MK-801 reduced the extent of cell death induced by the brief exposure to glutamate, NMDA, and kainate. By contrast, cell death induced by a 60-min exposure to kainate was not affected by MK-801. The electrophysiological study demonstrated that MK-801 abolished the whole-cell currents evoked by NMDA but had no effect on those induced by kainate or AMPA. CONCLUSION: These findings demonstrate that brief exposure to kainate induces cell death by way of activating NMDA receptors in cultured fetal retinal neurons and that NMDA receptors are the predominant route of fetal retinal neurotoxicity induced by brief glutamate exposure.

Animals↗
PubMed2000

Accumulation of N-acetyl-L-aspartate in the brain of the tremor rat, a mutant exhibiting absence-like seizure and spongiform degeneration in the central nervous system.

The tremor rat is a mutant that exhibits absence-like seizure and spongiform degeneration in the CNS. By positional cloning, a genomic deletion was found within the critical region in which the aspartoacylase gene is located. Accordingly, no aspartoacylase expression was detected in any of the tissues examined, and abnormal accumulation of N-acetyl-L-aspartate (NAA) was shown in the mutant brain, in correlation with the severity of the vacuole formation. Therefore, the tremor rat may be regarded as a suitable animal model of human Canavan disease, characterized by spongy leukodystrophy that is caused by aspartoacylase deficiency. Interestingly, direct injection of NAA into normal rat cerebroventricle induced 4- to 10-Hz polyspikes or spikewave-like complexes in cortical and hippocampal EEG, concomitantly with behavior characterized by sudden immobility and staring. These results suggested that accumulated NAA in the CNS would induce neuroexcitation and neurodegeneration directly or indirectly.

Amidohydrolases↗
PubMed2000

Effect of hydrogen peroxide on guinea pig nasal mucosa vasculature.

The effect of hydrogen peroxide (H2O2) on guinea pig nasal mucosa vasculature was studied by in vitro assay. H2O2 elicited relaxation of guinea pig nasal mucosa strips precontracted with phenylephrine in a concentration-dependent manner. The relaxant response to H2O2 was abolished in the presence of catalase. Preincubation of the strips with N(G)-nitro-L-arginine methyl ester or methylene blue significantly attenuated the relaxant responses elicited by H2O2. Fluorescence caused by DAF-2 DA, a fluorescence indicator for nitric oxide, was observed along the nasal mucosa vasculature in response to H2O2. These results suggest that H2O2 induced relaxation of the guinea pig nasal mucosa vasculature and that this relaxation is mediated by the NO/cGMP pathway.

Animals↗
PubMed1999

Cholinergic and glutamatergic transmission in medial vestibular nucleus neurons responding to lateral roll tilt in rats.

The responses of the medial vestibular nucleus (MVN) neurons to lateral tilt and the neurotransmitters mediating otolith information to MVN neurons were investigated using rats. A computer-operated goniometer was tilted 20 degrees clockwise and counterclockwise at an angular speed of 5 degrees /s and paused in the inclined positions for 10 s to record neuronal responses in the static phase. The 185 MVN neurons recorded were classified into eight types according to their responses to tilt (alpha, beta, gamma, delta, epsilon, zeta, eta and theta). A majority showed increased firing in response to ipsilateral tilting and decreased firing in response to contralateral tilting (alpha type: 31.4%) or exhibited the reverse pattern (beta type: 36.8%). Further, other groups of neurons increased (gamma type) or decreased (delta type) firing rates to either side tilting and increased (epsilon and zeta type) or decreased (eta and theta type) firing only on one side. Atropine or L-glutamic acid diethyl ester hydrochloride (GDEE) applied microiontophoretically antagonized tilt-induced firing of alpha type neurons in 58.8% or 60.0%, respectively, and of beta type neurons in 66.7% or 58.3%, respectively. When the effects of atropine and GDEE were examined in the same neurons, antagonizing effects of both drugs on tilt-induced firing were obtained in 28.6% and 40.0% of alpha and beta type neurons, respectively. These results suggest that both acetylcholine and glutamate act as neurotransmitters in the transmission of otolith information to most MVN neurons.

Animals↗
PubMed1999

Attenuation by PACAP of glutamate-induced neurotoxicity in cultured retinal neurons.

The effects of pituitary adenylate cyclase activating polypeptides (PACAPs: PACAP27, PACAP38) on glutamate-induced neurotoxicity were examined using cultured retinal neurons obtained from 3- to 5-day old Wistar rats. Cell viability was evaluated by double staining with fluorescein diacetate and propidium iodide. Effects of PACAPs on the increase in intracellular Ca(2+) concentration ([Ca(2+)](i)) in retinal neurons was investigated using the Ca(2+) image analyzing system with fura-2. The cAMP contents and the mitogen-activated protein (MAP) kinase activity in retinal cultures were measured by radioimmunoassay. Concomitant application of PACAPs (10 nM-1 microM) with glutamate (1 mM) for 10 min inhibited the delayed death of retinal neurons, which was observed 24 h after glutamate (1 mM) treatment in a dose-dependent manner. Protection by PACAPs (100 nM) against glutamate-induced neurotoxicity was antagonized by PACAP6-38 (1 microM), a PACAP antagonist, and H-89 (1 microM), a protein kinase A (PKA) inhibitor. However, PACAPs did not affect the glutamate-induced increase in [Ca(2+)](i), but PACAPs (1-100 nM) increased the cAMP levels in a dose-dependent manner. In addition, activation of MAP kinase by PACAP38 (1 microM) was inhibited by simultaneous application with H-89 (1 microM). These findings suggest that PACAPs attenuate glutamate-induced delayed neurotoxicity in cultured retinal neurons by activating MAP kinase through the activation of cAMP-stimulated PKA.

Animals↗
PubMed1999

Rat retinal ganglion cells culture enriched with the magnetic cell sorter.

The magnetic cell sorter (MACS) technique was applied to isolate retinal ganglion cells (RGCs) for culture. RGCs were labeled retrogradely with 1.1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate (Dil). Subsequently retinal cell suspensions were incubated with biotinylated anti-rat Thy-1 antibody and MACS Streptavidin MicroBeads, and then applied onto the column in the magnetic fields. Cells attached on the column were flashed out without magnetism and plated on glass cover slips. RGCs were enriched to 31.0% of all cells with MACS from 0.55% before applying onto the magnetic column. Mean diameters of Dil-labeled cells were significantly larger than those of unlabeled cells. All cells with soma diameter over 11 microm were labeled. The number of viable RGCs were counted in the 10 fields of six cultures at a magnification of x200; the mean numbers on the 2nd, 7th and 14th culture-day were 53+/-3, 24+/-2 and 21+/-3, respectively (mean +/- SEM, n = 6). Thus, the MACS technique was confirmed to be useful for enrichment of RGCs and long-term study of cultured RGCs.

Animals↗
PubMed1999

Inhibition by aripiprazole of dopaminergic inputs to striatal neurons from substantia nigra.

RATIONALE: Aripiprazole (OPC-14597) elicits both dopamine D(2) agonist and antagonist activities on dopaminergic neurons of the ventral tegmental area and nucleus accumbens neurons, respectively. However, the electrophysiological action of this drug on the striatal neurons is not clear. OBJECTIVE: Therefore, the present electrophysiological study was performed to determine if aripiprazole modified the striatal neurons as a D(2) receptor agonist or antagonist. METHODS: Spikes elicited by stimulation of pars compacta of the substantia nigra (SN) were extracellularly recorded from the striatal neurons with a glass microelectrode attached along a seven- barreled micropipette. Each barrel was filled with aripiprazole, quinpirole (D(2) receptor agonist), domperidone (D(2) receptor antagonist), glutamate or 2 M NaCl. The drugs were microiontophoretically applied on the neurons being recorded. RESULTS: The effects of aripiprazole on SN stimulation-induced spikes of striatal neurons that were inhibited by domperidone were examined. Microiontophoretic application of aripiprazole inhibited spikes elicited by SN stimulation in all 18 neurons tested in a dose-dependent manner. In addition, quinpirole-induced firing was inhibited by aripiprazole in all ten neurons tested. However, glutamate-induced spontaneous firing was not affected by aripiprazole in any of the ten neurons tested. CONCLUSIONS: These findings suggest that aripiprazole acts as a dopamine D(2) receptor antagonist on striatal neurons receiving excitatory inputs from the SN.

Animals↗
PubMed1999

Two phases of behavioral plasticity in rats following unilateral excitotoxic lesion of the hippocampus.

We investigated the effects of dizocilpine, a non-competitive N-methyl-D-aspartate receptor antagonist, on spatial reference and working memory in a radial arm maze task in rats with a unilateral hippocampal lesion. At a dose of 0.2 mg/kg to intact rats, dizocilpine significantly impaired both reference and working memory, and produced ataxia and impairment of food intake; at 0.1 mg/kg, dizocilpine had no effect on performance. Unilateral hippocampal lesion induced by quinolinic acid produced a marked working memory deficit concomitant with a slight but significant impairment of reference memory when mnemonic ability was examined one week after the lesion. The spatial memory deficits in the rats with a unilateral hippocampal lesion were ameliorated by repeated daily trainings over a 21-day period. Following recovery of the spatial memory deficits produced by the brain lesion (four weeks after the brain lesion), dizocilpine (0.1 mg/kg) significantly impaired both reference and working memory, without affecting general behavior or food intake in the brain-lesioned rats. An impairment of working memory, but not reference memory, by dizocilpine was observed six weeks after the brain lesion. However, the disrupting effect of dizocilpine at 0.1 mg/kg on spatial working memory had disappeared at eight weeks after the lesion. Ten weeks after the brain lesion, dizocilpine at 0.2 mg/kg was necessary to induce spatial memory impairment, which was accompanied by motor and food intake deficits, as in intact rats. In sham-operated rats, the dose-response effects of dizocilpine did not differ from those in intact rats at any time after the operation. These results suggest that two phases of behavioral plasticity take place, depending on demand, to compensate for brain dysfunction after the unilateral lesion of the hippocampus in rats.

Animals↗
PubMed1999

[Molecular mechanism underlying epileptic seizure: forwards development of novel drugs for untreatable epilepsy].

For the development of new drugs for hitherto untreatable epilepsy, it is necessary to clarify the basic pathophysiology involved in such epileptic seizures and find the target site. This review focused on molecular events related to the expression and expansion of the epileptic focus which are the target of novel antiepileptics. Immediate early genes such as c-fos followed by expression of nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) have been evidenced as initial important phenomena in the cascade of molecular systems that develop and complement the transient neuronal excitation to long-term neuronal plasticity. Non-receptor type tyrosine kinase Fyn in the Src family has been suggested to promote kindling development via tyrosine phosphorylation of the NMDA-receptor subunit, NR2B. The cause of abnormality in the inhibitory system is induced by lowering of glutamate-dependent GABA release in the epileptic focus within the hippocampus in human temporal epilepsy. This is probably attributed to a decrease in GABA transporters. Regarding abnormality of the excitatory system, there is an increase in glutamate release prior to convulsive seizures, an enhancement of NMDA receptor responsiveness and high levels of AMPA receptors related to convulsion after completion of kindling. In gene analysis of human familiar epilepsy, abnormalities and point mutations have recently been found in the following genes: KCNQ 2 and KCNQ3, coding for K+ channels; CHRNA4 of the nicotinic receptor subunit alpha 4; and the cystatin B gene. In epilepsy model mice, EL mice with several gene mutations known to be involved in the seizures, the El-1 gene contains an abnormality of the ceruloplasmin gene. SER (spontaneously epileptic rat: zi/zi, tm/tm), a double mutant, manifests a deletion of the region containing the aspartoacylase gene related to the tm gene. Since an increase in N-acetyl-L-aspartate (NAA) is observed in the SER brain, NAA may serve to evoke seizures.

Amidohydrolases↗
PubMed1999

[The function of sigma receptors--electrophysiological approach].

The functions of sigma (sigma) receptors were reviewed based on electrophysiological studies. Systemic administration of sigma ligands reportedly produces a variety of effects on dopamine (DA) neurons. In the mesolimbic DA system, (+)SKF-10,047 suppressed activities of the ventral tegmental area. In the substantia nigra, DTG also suppressed these activities, while BMY-14802 increased the activity of neurons. In the cerebellum, however, activities of Purkinje cells were suppressed by locally applied DTG, with probable involvement of the catecholaminergic system. This effect on Purkinje cells may explain the action of sigma ligands on the motor system. In the hippocampus, neuronal activities were inhibited by SR31742A in vivo (CA3 region) and by (+)SKF10,047 in vitro (CA1 region). DTG at high concentration (1 mM) completely suppressed population spikes (PS) in the CA1 region of hippocampal slice preparations. In our experiments, a novel sigma ligand, OPC-24439, suppressed PS in CA1 at concentrations of 1-100 microM. However, NMDA-induced neuronal firings in CA3 in vivo were augmented by low doses of DTG in a haloperidol-sensitive manner, but high doses were ineffective. In contrast, non-NMDA responses were not affected by DTG. In addition, several sigma ligands having no effect on the NMDA response have been reported. In addition, endogenous ligands, neuropeptide Y and dehydroepiandrosterone, augmented the NMDA-induced firing. In whole-cell patch clamp recording, NMDA-induced currents were suppressed by a relatively higher concentration of DTG in a concentration-dependent manner, while non-NMDA responses were only slightly suppressed. These findings suggest that effects of sigma ligands on NMDA receptor responses are biphasic, and sigma ligands may modulate memory and learning and suppress neuronal death by anoxia. In addition, sigma ligands are also reported to suppress Ca2+ channels in hippocampal culture neurons and induce current by closing K+ channels in NCB-20 cells. Thus, sigma receptors may be involved in the modulation of a variety of neurons that relate to psychiatric function and plasticity.

Animals↗
PubMed1999

[Effects of OPC-24439, a sigma ligand, on neuronal activities in the hippocampus].

Sigma receptors in the central nervous system have been considered to play an important role in the modulation of mental diseases and memory/learning. However, the physiological function of sigma receptors still remains unknown. To elucidate physiological functions of the sigma receptors in modulation of neuronal activities, the effects of OPC-24439 (a sigma receptor ligand) on neuronal activities in hippocampal slices were studied with electrophysiological methods. Hippocampal slices (thickness ca. 450 microns) were prepared from male Wistar rats (4-7 weeks of age). In extracellular recording, population spikes in the CA1 region evoked by stimulation applied to the Schaffer collateral/commissural fibers were suppressed by OPC-24439 (1-100 microM) in a dose-dependent manner. This inhibition was antagonized by simultaneously applied haloperidol at 1 microM. In intracellular recording experiments, OPC-24439 (100 microM) did not affect the resting membrane potentials of neurons recorded. In addition, OPC-24439 had no effects on depolarization and firing induced by glutamate. These results indicate that sigma receptor activation caused suppression of neuronal activities in the hippocampus via the sigma receptors. This inhibition probably mediated via the suppression of ion channels that are not related to membrane potentials on post-synaptic neurons and/or sigma receptors on pre-synaptic neurons or interneurons.

Animals↗
PubMed1999

Mechanism underlying the therapeutic effects of electroconvulsive therapy (ECT) on depression.

Electroconvulsive therapy (ECT) is used to treat drug-resistant depressive disorders. The results of studies on the mechanism underlying the effectiveness of ECT on depression are still controversial. ECT stimulus is usually larger than the threshold of induction of seizures and activation of whole-brain is believed to be necessary to produce therapeutic effects. A single ECT session induces alterations of the electroencephalogram (EEG) including initial epileptic discharges, then slow waves, and finally flattened EEG. Repeated ECT results in an increasing number of slower waves in the EEG for as long as a month. ECT-induced changes in various neurotransmitter systems have also been reported. Serotonin (5-hydroxytryptamine, 5-HT) is one of the most important neurotransmitters involved in depressive illness, and ECT alters several 5-HT-receptor subtypes in the central nervous system. 5-HT1A receptors in post-synaptic neurons are sensitized by repeated ECT, but those in pre-synaptic neurons (auto-receptors) are not changed. In addition, our electrophysiological studies have shown that ECT increases sensitivity to 5-HT of 5-HT3 receptors in the hippocampus, resulting in an increase in release of neurotransmitters such as glutamate and gamma-aminobutyric acid. In contrast, ECT decreases the auto-receptor functions in noradrenergic and dopaminergic neurons in the locus coeruleus and substantia nigra, respectively, resulting in an increase in release of noradrenaline and dopamine. In conclusion, 5-HT1A-receptor sensitization may be important for explaining the effectiveness of ECT, as this change induces a decrease in the number of 5-HT2A receptors that are elevated in depressive patients. Facilitation of neurotransmitter releases due to 5-HT3-receptor sensitization by ECT may also play an important role in effective treatment of depressive patients refractory to therapeutic drugs.

Animals↗
PubMed1999

[Detection of numerical aberrations in chromosomes by fluorescence in situ hybridization in fine needle aspirates in the preoperative diagnosis of cancer].

Fine needle aspiration (FNA) samples were obtained from 176 breast tumors suspected of malignancy, which were then subjected to conventional cytological and fluorescence in situ hybridization (FISH) analyses using the centromeric probes for chromosomes 1, 11, and 17. Histological examination revealed 157 breast cancers and 19 benign diseases (ten fibroadenomas, six intraductal papillomas, one intracystic papilloma, and two ADH). Sensitivity, specificity, and diagnostic accuracy were 85.4% 94.7%, and 86.4%, respectively, for cytology and 90.4%, 100%, and 91.5%, respectively, for FISH. These results demonstrate that FISH diagnosis of FNA samples has a diagnostic accuracy comparable to that of conventional cytology.

Biopsy, Needle↗
PubMed1998

Protective effects of vasoactive intestinal peptide against delayed glutamate neurotoxicity in cultured retina.

The effects of vasoactive intestinal peptide (VIP) on glutamate-induced delayed death were examined using the primary cultures of rat retinal neurons. Effects of VIP on glutamate-induced neurotoxicity were evaluated by double staining with fluorescein diacetate and propidium iodide. Glutamate (1 mM) was applied to the culture for 10 min in the presence and absence of VIP, and visible cells enumerated 24 h after culture in normal medium. Effects of VIP on increase in the intracellular Ca2+ concentration and currents induced by glutamate in retinal neurons were investigated using the Ca2+ image analyzing system with fura-2 and whole-cell patch-clamp recording, respectively. The cAMP contents in retinal cultures were measured by radioimmunoassay. VIP (10 nM-1 microM) dose-dependently protected against glutamate-induced neurotoxicity in cultured retinal neurons. Protection by VIP (100 nM) against glutamate (1 mM)-induced neurotoxicity was antagonized by VIP6-28 (1 microM), a VIP antagonist, and H-89 (100 nM and 1 microM), a protein kinase A inhibitor. However, VIP had no effect on glutamate-induced inward currents nor glutamate-induced increase in the intracellular Ca2+ concentration. A 10-min exposure of VIP (100 nM) with glutamate (1 mM) resulted in an increase in the cAMP level to 446+/-58 from 22+/-1 pmol/mg protein. These findings suggest that VIP protects against the glutamate-induced neurotoxicity in retinal cultures by elevating the cAMP level via VIP receptors and thereby activating protein kinase A.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1998

Radiation Complications Following Breast Conserving Therapy.

BACKGROUND: Breast conserving therapy is being established as a standard therapeutic procedure for early breast cancer in Japan. However, the indications of radiotherapy and a standardized therapeutic procedure have not been established yet. In this study, complications following radiotherapy were evaluated in patients who had previously undergone breast conserving therapy at Tokushima University Hospital. METHODS From October 1989 to March 1996, 60 women with stage I or II breast cancer underwent radiation therapy after breast conserving surgery, and all patients were followed-up for a median of 27 months. Radiation morbidity scoring of the breast and adjacent organs was performed using the toxity criteria of the Radiation Therapy Oncology Group (RTOG) and European Organization for Research andTreatment of Cancer (EORTC). RESULTS: Only 1 patient developed local recurrence, and no distant metastasisor death was observed. The cause of recurrence in 1 case was considered to be due to extended intraductal component. Although transient dermal reaction was induced by irradiation of the breast, no side effects that may cause cosmetic problems were found. No serious radiation complications were found in the lungs, ribs, heart or other adjacent organs. CONCLUSION: The adverse reactions caused by irradiation does not reduce the merit of combined use of radiation therapy in breast conserving therapy, and therefore, are not the hesitation factor in application of radiotherapy.

Journal Article↗
PubMed1998

Current Status of Screening for Breast Cancer and Tasks for Introduction of Mammographic Screening in Japan.

In the United States and Europe the high mortality of breast cancer has been significantly reduced by mammographic screening of women aged over 50 years, theeffectiveness of which has been documented in many reports. In contrast, the effectiveness of such screening in women aged from 40 to 49 remains controversial.In Japan, breast cancer screening has consisted of physical examination alone, with inspection and palpation. Thus, more than half of the patients with breast cancer detected by this screening system are already aware of their lumps, the detection rate has been a little less than 0.1%, and the proportion of early-stage disease among breast cancers is only about 50%. It is difficult to detect breast cancer consisting of non-palpable tumors by physical examination, and the lowsensitivity of this screening method has been pointed out. In Japan, there is no difference in overall survival between cases detected by screening and those detected in outpatient clinics. The results of the mammographic screening trial performed in Miyagi and Tokushima, which were promising in terms of proportions of early-stage cancer and no nodal involvement, strongly suggest its usefulness in Japan as well as in other countries. However, long-term results are not yet available. It is advocated that screening for breast cancer should be performed by means of mammography to improve the screening sensitivity, and increase the proportion of early-stage breast cancers. Mammo-graphic screening, either mammography and physical examination separately or simultanously in combination, has been effective for women aged over 50 years in Japan. However, with regard to those aged under 49 years, further studies are needed.

Journal Article↗
PubMed1998

Suppression by topiramate of epileptiform burst discharges in hippocampal CA3 neurons of spontaneously epileptic rat in vitro.

Topiramate, a novel antiepileptic drug, inhibits the seizures of spontaneously epileptic rat (SER), a double mutant (zi/zi, tm/tm) which exhibits both tonic convulsion and absence-like seizures from the age of 8-weeks. Hippocampal CA3 pyramidal neurons in SER show a long-lasting depolarization shift with accompanying repetitive firing when a single electrostimulation is delivered to the mossy fibers in vitro. The effects of topiramate on the excitability of CA3 pyramidal neurons in SER were examined to elucidate the mechanism underlying the antiepileptic action. Intracellular recordings were performed in 23 hippocampal slice preparations of 16 SER aged 8-17 weeks. Topiramate (10-100 microM) dose-dependently inhibited the depolarizing shifts with repetitive firing induced by mossy fiber stimulation without affecting the first spike and resting membrane potentials in hippocampal CA3 neurons of SER. Higher dose of topiramate (100 microM) sometimes inhibited the first spike, and decreased excitatory postsynaptic potentials in the SER CA3 neurons. However, topiramate up to 100 microM did not affect the single action potential elicited by the stimulation in the hippocampal CA3 neurons of age-matched Wistar rat devoid of the seizure. Application of topiramate (100 microM) did not significantly affect the firing induced by depolarizing pulse applied in the CA3 neurons of the SER. In addition, topiramate (100 microM) had no effects on the Ca2+ spike induced by intracellularly applied depolarizing pulse in the presence of tetrodotoxin and tetraethylammonium. In contrast, a dose-dependent inhibition of depolarization and repetitive firing induced by bath application of glutamate in CA3 pyramidal neurons was obtained with topiramate (10-100 microM). Furthermore, topiramate (100 microM) decreased the number of miniature postsynaptic potential of CA3 pyramidal neurons of SER. In patch clamp whole cell recording using acutely dissociated hippocampal CA3 neurons from SER aged 8-weeks and age-matched normal Wistar rats, there were no remarkable effects on voltage dependent Ca2+ current with topiramate up to 300 microM in either animal; the current was completely blocked by Cd2+ at a concentration of 1 mM. These findings suggest that topiramate inhibits release of glutamate from the nerve terminals and/or abnormal firing of the CA3 pyramidal neurons of SER by mainly blocking glutamate receptors in the neurons.

Action Potentials↗