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Susan R. Weiss - One of the best experts on this subject based on the ideXlab platform.

  • Lamotrigine treatment during Amygdala-Kindled Seizure development fails to inhibit Seizures and diminishes subsequent anticonvulsant efficacy.
    Epilepsia, 2000
    Co-Authors: Terri Postma, Robert M. Post, Eckart Krupp, Susan R. Weiss
    Abstract:

    PURPOSE Lamotrigine (LTG) is an anticonvulsant that is currently in use for the treatment of various Seizure disorders and that shows promise in the treatment of affective illness. LTG is also effective in the suppression of Amygdala-Kindled Seizures. Because many drugs show a differential efficacy profile as a function of the phase of kindling evolution, we evaluated LTG for its potential antiepileptogenic effects on the development of Amygdala-Kindled Seizures. METHODS In two separate studies, LTG (5 or 15 mg/kg versus vehicle) was administered before each daily amygdala stimulation (biphasic square wave pulses, 100 pulse pairs per second for a total of 0.5 second, 1-millisecond pulse width) at an intensity of 50 microA over the AD threshold. Seizure development was assessed, as well as the effect of this pretreatment on subsequent efficacy of LTG on completed kindled Seizures. RESULTS LTG at 5 mg/kg failed to block Seizure development. At 15 mg/kg, LTG paradoxically enhanced Seizure development and produced running fits in four of the nine animals tested. Animals previously treated with either dose of LTG during kindling development showed a diminished response to the anticonvulsant effects of LTG on fully kindled Seizures compared with the vehicle-treated controls. CONCLUSIONS Although LTG possesses potent anticonvulsant effects on completed Amygdala-Kindled Seizures, it is either without effect (5 mg/kg) or facilitates (15 mg/kg) the initial phase of kindling development. In addition, exposure to LTG during kindled Seizure development leads to a reduced subsequent response to the drug in fully kindled animals. These observations parallel those with carbamazepine and suggest that different stages of kindling (epileptogenesis versus fully manifest Seizures) may have different underlying neural mechanisms that require distinct pharmacotherapies.

  • Tolerance to the anticonvulsant effects of lamotrigine on amygdala kindled Seizures: cross-tolerance to carbamazepine but not valproate or diazepam.
    Experimental neurology, 2000
    Co-Authors: Eckart Krupp, Robert M. Post, Terri Heynen, Susan R. Weiss
    Abstract:

    Using an Amygdala-Kindled Seizure paradigm, we evaluated the acute and chronic anticonvulsant effects of lamotrigine (LTG). Lamotrigine produced dose-dependent inhibitory effects on Seizure stage, afterdischarge (AD), and Seizure duration. Lamotrigine (15 mg/kg) also increased the afterdischarge and Seizure thresholds. Following repeated LTG administration and stimulation at 48-h intervals, tolerance developed to LTG's (15 mg/kg) anticonvulsant effects, and cross-tolerance was observed to the anticonvulsant effects of carbamazepine (CBZ, 15 mg/kg). In a separate group of kindled rats, CBZ (15 mg/kg) was repeatedly administered to induce tolerance. This led to a partial cross-tolerance to LTG, manifesting as an increased rate of tolerance development to LTG, and Seizures following the first injection in some animals, which were not observed in CBZ-nontolerant controls. When these rats were made fully tolerant to LTG and then exposed to higher doses of LTG (30 and 50 mg/kg), no anticonvulsant effects were observed. In contrast, higher doses of CBZ (30 mg/kg) did restore efficacy in CBZ-tolerant animals. Cross-tolerance from LTG to valproate and diazepam was not observed, although cross-tolerance from CBZ to valproate has been reported previously. These data suggest that LTG has both shared and distinct anticonvulsant mechanisms from those of CBZ on Amygdala-Kindled Seizures. The implications of these results for clinical therapeutics remain to be evaluated.

  • Apoptosis of hippocampal neurons after amygdala kindled Seizures
    Brain research. Molecular brain research, 1998
    Co-Authors: Li-xin Zhang, Susan R. Weiss, Mark A. Smith, Robert M. Post
    Abstract:

    Seizure-induced neuronal damage may involve both excitotoxic and apoptotic (programmed cell death) mechanisms. In the present study, we used an amygdala kindled Seizure model to study whether apoptotic cell death occurs. To evaluate apoptosis, we counted the numbers of cells that had DNA fragments labeled at the 3' end with digoxigenin using terminal transferase (ApopTag, Oncor). Additionally, the expression of Bax and Bcl-2, two genes associated with apoptotic cell death, was also measured following kindled Seizures. We found that the number of ApopTag-positive cells in the hippocampus increased 30.4% after one kindled Seizure and 82.5% after 20 Seizures compared to sham controls. The ApopTag-labeled cells could be mainly interneurons of the hippocampal formation, although additional studies are required. Preferential vulnerability of inhibitory interneurons is consistent with previous studies on Seizure-induced cell loss. These results, coupled with our findings that the ratio of Bax/Bcl-2 expression is increased in the hippocampus by Seizures, suggest that apoptosis of hippocampal interneurons may lead to dysinhibition in the hippocampus and increased Seizure susceptibility.

  • Contingent tolerance to carbamazepine is associated with lowering of Amygdala-Kindled Seizure thresholds.
    Experimental neurology, 1991
    Co-Authors: Susan R. Weiss, Kurt Haas, Robert M. Post
    Abstract:

    Amygdala-Kindled Seizure thresholds were studied in animals which were or were not tolerant to the anticonvulsant effects of carbamazepine. The Seizure threshold was defined as the lowest current that elicited a major motor Seizure (stage 3 or greater). Amygdala-Kindled rats received carbamazepine, once daily, either before each electrical stimulation (carba-before) or after each stimulation (carba-after). The rats given carbamazepine before, but not after, each once-daily kindling stimulation became tolerant to its anticonvulsant effects. Following this manipulation, Seizure thresholds were redetermined in both groups of animals while medication-free. The carba-before (i.e., tolerant) animals showed a decreased Seizure threshold, while the carba-after (i.e., nontolerant) animals showed no change. Tolerance to carbamazepine was reversed by giving the rats kindled Seizures for a period of 7 days without drug; nontolerant animals received the same stimulation and Seizures. When Seizure thresholds were reevaluated, the carba-before animals (now not tolerant) had returned to their pretolerance values, while the carba-after group again showed no change. This effect of carbamazepine tolerance and its reversal being associated with respective decreases and increases in basal Seizure threshold was replicated two more times. In each case the change in the generalized Seizure threshold mirrored the change in responsivity of the animals to carbamazepine. These findings, consistent with the formulations of Siegel regarding conditioned compensatory response mechanisms mediating contingent drug tolerance, may have important clinical and theoretical implications.

Robert M. Post - One of the best experts on this subject based on the ideXlab platform.

  • Lamotrigine treatment during Amygdala-Kindled Seizure development fails to inhibit Seizures and diminishes subsequent anticonvulsant efficacy.
    Epilepsia, 2000
    Co-Authors: Terri Postma, Robert M. Post, Eckart Krupp, Susan R. Weiss
    Abstract:

    PURPOSE Lamotrigine (LTG) is an anticonvulsant that is currently in use for the treatment of various Seizure disorders and that shows promise in the treatment of affective illness. LTG is also effective in the suppression of Amygdala-Kindled Seizures. Because many drugs show a differential efficacy profile as a function of the phase of kindling evolution, we evaluated LTG for its potential antiepileptogenic effects on the development of Amygdala-Kindled Seizures. METHODS In two separate studies, LTG (5 or 15 mg/kg versus vehicle) was administered before each daily amygdala stimulation (biphasic square wave pulses, 100 pulse pairs per second for a total of 0.5 second, 1-millisecond pulse width) at an intensity of 50 microA over the AD threshold. Seizure development was assessed, as well as the effect of this pretreatment on subsequent efficacy of LTG on completed kindled Seizures. RESULTS LTG at 5 mg/kg failed to block Seizure development. At 15 mg/kg, LTG paradoxically enhanced Seizure development and produced running fits in four of the nine animals tested. Animals previously treated with either dose of LTG during kindling development showed a diminished response to the anticonvulsant effects of LTG on fully kindled Seizures compared with the vehicle-treated controls. CONCLUSIONS Although LTG possesses potent anticonvulsant effects on completed Amygdala-Kindled Seizures, it is either without effect (5 mg/kg) or facilitates (15 mg/kg) the initial phase of kindling development. In addition, exposure to LTG during kindled Seizure development leads to a reduced subsequent response to the drug in fully kindled animals. These observations parallel those with carbamazepine and suggest that different stages of kindling (epileptogenesis versus fully manifest Seizures) may have different underlying neural mechanisms that require distinct pharmacotherapies.

  • Tolerance to the anticonvulsant effects of lamotrigine on amygdala kindled Seizures: cross-tolerance to carbamazepine but not valproate or diazepam.
    Experimental neurology, 2000
    Co-Authors: Eckart Krupp, Robert M. Post, Terri Heynen, Susan R. Weiss
    Abstract:

    Using an Amygdala-Kindled Seizure paradigm, we evaluated the acute and chronic anticonvulsant effects of lamotrigine (LTG). Lamotrigine produced dose-dependent inhibitory effects on Seizure stage, afterdischarge (AD), and Seizure duration. Lamotrigine (15 mg/kg) also increased the afterdischarge and Seizure thresholds. Following repeated LTG administration and stimulation at 48-h intervals, tolerance developed to LTG's (15 mg/kg) anticonvulsant effects, and cross-tolerance was observed to the anticonvulsant effects of carbamazepine (CBZ, 15 mg/kg). In a separate group of kindled rats, CBZ (15 mg/kg) was repeatedly administered to induce tolerance. This led to a partial cross-tolerance to LTG, manifesting as an increased rate of tolerance development to LTG, and Seizures following the first injection in some animals, which were not observed in CBZ-nontolerant controls. When these rats were made fully tolerant to LTG and then exposed to higher doses of LTG (30 and 50 mg/kg), no anticonvulsant effects were observed. In contrast, higher doses of CBZ (30 mg/kg) did restore efficacy in CBZ-tolerant animals. Cross-tolerance from LTG to valproate and diazepam was not observed, although cross-tolerance from CBZ to valproate has been reported previously. These data suggest that LTG has both shared and distinct anticonvulsant mechanisms from those of CBZ on Amygdala-Kindled Seizures. The implications of these results for clinical therapeutics remain to be evaluated.

  • Apoptosis of hippocampal neurons after amygdala kindled Seizures
    Brain research. Molecular brain research, 1998
    Co-Authors: Li-xin Zhang, Susan R. Weiss, Mark A. Smith, Robert M. Post
    Abstract:

    Seizure-induced neuronal damage may involve both excitotoxic and apoptotic (programmed cell death) mechanisms. In the present study, we used an amygdala kindled Seizure model to study whether apoptotic cell death occurs. To evaluate apoptosis, we counted the numbers of cells that had DNA fragments labeled at the 3' end with digoxigenin using terminal transferase (ApopTag, Oncor). Additionally, the expression of Bax and Bcl-2, two genes associated with apoptotic cell death, was also measured following kindled Seizures. We found that the number of ApopTag-positive cells in the hippocampus increased 30.4% after one kindled Seizure and 82.5% after 20 Seizures compared to sham controls. The ApopTag-labeled cells could be mainly interneurons of the hippocampal formation, although additional studies are required. Preferential vulnerability of inhibitory interneurons is consistent with previous studies on Seizure-induced cell loss. These results, coupled with our findings that the ratio of Bax/Bcl-2 expression is increased in the hippocampus by Seizures, suggest that apoptosis of hippocampal interneurons may lead to dysinhibition in the hippocampus and increased Seizure susceptibility.

  • Differential regional and time course increases in thyrotropin-releasing hormone, neuropeptide Y and enkephalin mRNAs following an amygdala kindled Seizure.
    Brain research. Molecular brain research, 1994
    Co-Authors: Jeffrey B. Rosen, Su-yong Kim, Robert M. Post
    Abstract:

    Previous studies have shown that neuropeptide mRNA expression is altered in the dentate gyrus, and pyriform, entorhinal and perirhinal cortices following amygdala kindling. However, because rats were kindled every day and some mRNA alterations last longer than 24 h, a true measure of the alterations induced by a single Seizure was confounded by the previous day's Seizure. To circumvent this problem, rats were fully kindled, had six days without stimulation, and then were given one more Seizure. Rats were sacrificed either 4 h, 24 h or 4 days after this last Seizure. The levels of mRNAs for TRH, NPY and ENK were measured in the dentate gyrus and limbic cortices. Four hours after a Seizure, TRH and NPY mRNAs were maximally increased in the dentate gyrus granule layer, but returned to baseline levels by 24 h. In contrast, 4 h after a Seizure, TRH and NPY mRNAs were not, or only slightly, increased in the pyriform, entorhinal and perirhinal cortices, but significantly elevated 24 h after a Seizure. ENK mRNA was increased both 4 and 24 h after a Seizure in the pyriform, entorhinal and perirhinal cortices but showed no increases in the dentate gyrus at any time. By 4 days, peptide mRNA levels returned to baseline, except for ENK mRNA in the pyriform cortex. These results demonstrate a non-uniform and complex pattern of peptide mRNA expression following an amygdala kindled Seizure. They further suggest that regional and time course differences in gene transcription and expression may be important factors in understanding both the transient, adaptive anticonvulsant and longer lasting proconvulsant effects of these neuropeptides.

  • Contingent tolerance to carbamazepine is associated with lowering of Amygdala-Kindled Seizure thresholds.
    Experimental neurology, 1991
    Co-Authors: Susan R. Weiss, Kurt Haas, Robert M. Post
    Abstract:

    Amygdala-Kindled Seizure thresholds were studied in animals which were or were not tolerant to the anticonvulsant effects of carbamazepine. The Seizure threshold was defined as the lowest current that elicited a major motor Seizure (stage 3 or greater). Amygdala-Kindled rats received carbamazepine, once daily, either before each electrical stimulation (carba-before) or after each stimulation (carba-after). The rats given carbamazepine before, but not after, each once-daily kindling stimulation became tolerant to its anticonvulsant effects. Following this manipulation, Seizure thresholds were redetermined in both groups of animals while medication-free. The carba-before (i.e., tolerant) animals showed a decreased Seizure threshold, while the carba-after (i.e., nontolerant) animals showed no change. Tolerance to carbamazepine was reversed by giving the rats kindled Seizures for a period of 7 days without drug; nontolerant animals received the same stimulation and Seizures. When Seizure thresholds were reevaluated, the carba-before animals (now not tolerant) had returned to their pretolerance values, while the carba-after group again showed no change. This effect of carbamazepine tolerance and its reversal being associated with respective decreases and increases in basal Seizure threshold was replicated two more times. In each case the change in the generalized Seizure threshold mirrored the change in responsivity of the animals to carbamazepine. These findings, consistent with the formulations of Siegel regarding conditioned compensatory response mechanisms mediating contingent drug tolerance, may have important clinical and theoretical implications.

Eckart Krupp - One of the best experts on this subject based on the ideXlab platform.

  • Lamotrigine treatment during Amygdala-Kindled Seizure development fails to inhibit Seizures and diminishes subsequent anticonvulsant efficacy.
    Epilepsia, 2000
    Co-Authors: Terri Postma, Robert M. Post, Eckart Krupp, Susan R. Weiss
    Abstract:

    PURPOSE Lamotrigine (LTG) is an anticonvulsant that is currently in use for the treatment of various Seizure disorders and that shows promise in the treatment of affective illness. LTG is also effective in the suppression of Amygdala-Kindled Seizures. Because many drugs show a differential efficacy profile as a function of the phase of kindling evolution, we evaluated LTG for its potential antiepileptogenic effects on the development of Amygdala-Kindled Seizures. METHODS In two separate studies, LTG (5 or 15 mg/kg versus vehicle) was administered before each daily amygdala stimulation (biphasic square wave pulses, 100 pulse pairs per second for a total of 0.5 second, 1-millisecond pulse width) at an intensity of 50 microA over the AD threshold. Seizure development was assessed, as well as the effect of this pretreatment on subsequent efficacy of LTG on completed kindled Seizures. RESULTS LTG at 5 mg/kg failed to block Seizure development. At 15 mg/kg, LTG paradoxically enhanced Seizure development and produced running fits in four of the nine animals tested. Animals previously treated with either dose of LTG during kindling development showed a diminished response to the anticonvulsant effects of LTG on fully kindled Seizures compared with the vehicle-treated controls. CONCLUSIONS Although LTG possesses potent anticonvulsant effects on completed Amygdala-Kindled Seizures, it is either without effect (5 mg/kg) or facilitates (15 mg/kg) the initial phase of kindling development. In addition, exposure to LTG during kindled Seizure development leads to a reduced subsequent response to the drug in fully kindled animals. These observations parallel those with carbamazepine and suggest that different stages of kindling (epileptogenesis versus fully manifest Seizures) may have different underlying neural mechanisms that require distinct pharmacotherapies.

  • Tolerance to the anticonvulsant effects of lamotrigine on amygdala kindled Seizures: cross-tolerance to carbamazepine but not valproate or diazepam.
    Experimental neurology, 2000
    Co-Authors: Eckart Krupp, Robert M. Post, Terri Heynen, Susan R. Weiss
    Abstract:

    Using an Amygdala-Kindled Seizure paradigm, we evaluated the acute and chronic anticonvulsant effects of lamotrigine (LTG). Lamotrigine produced dose-dependent inhibitory effects on Seizure stage, afterdischarge (AD), and Seizure duration. Lamotrigine (15 mg/kg) also increased the afterdischarge and Seizure thresholds. Following repeated LTG administration and stimulation at 48-h intervals, tolerance developed to LTG's (15 mg/kg) anticonvulsant effects, and cross-tolerance was observed to the anticonvulsant effects of carbamazepine (CBZ, 15 mg/kg). In a separate group of kindled rats, CBZ (15 mg/kg) was repeatedly administered to induce tolerance. This led to a partial cross-tolerance to LTG, manifesting as an increased rate of tolerance development to LTG, and Seizures following the first injection in some animals, which were not observed in CBZ-nontolerant controls. When these rats were made fully tolerant to LTG and then exposed to higher doses of LTG (30 and 50 mg/kg), no anticonvulsant effects were observed. In contrast, higher doses of CBZ (30 mg/kg) did restore efficacy in CBZ-tolerant animals. Cross-tolerance from LTG to valproate and diazepam was not observed, although cross-tolerance from CBZ to valproate has been reported previously. These data suggest that LTG has both shared and distinct anticonvulsant mechanisms from those of CBZ on Amygdala-Kindled Seizures. The implications of these results for clinical therapeutics remain to be evaluated.

Kazufumi Akiyama - One of the best experts on this subject based on the ideXlab platform.

  • Long-lasting increase in protein kinase C activity in the hippocampus of Amygdala-Kindled rat.
    Brain research, 1995
    Co-Authors: Kazufumi Akiyama, Mitsuhiro Ono, Ichiro Kohira, Akihiro Daigen, Takeshi Ishihara, Shigetoshi Kuroda
    Abstract:

    Previous studies have demonstrated that membrane-associated protein kinase C (PKC) activities in the right and left hippocampus of rats kindled from the left hippocampus increased significantly at 4 weeks [9] and 4 months [22] after the last Seizure compared with those in matched control rats. In this study, we investigated the effect of kindling from the left amygdala on PKC activities in the amygdala/pyriform cortex and hippocampus at long Seizure-free intervals (4 and 16 weeks) from the last Amygdala-Kindled Seizure. Membrane-associated PKC activity of the kindled group increased significantly only in the left hippocampus compared with the left side control (the left hippocampus of rats subjected to a sham operation) at 4 weeks (by 34%, P < 0.03) and 16 weeks (by 24%, P < 0.05) after the last Seizure. There was no significant alteration in the membrane-associated PKC activity of the kindled group in the right hippocampus or amygdala/pyriform cortex in any Seizure-free interval after the last amygdala Seizure. Cytosolic PKC activity did not differ between the kindled and control groups in any brain region examined in any Seizure-free interval. At 16 weeks after the last Seizure, the PKC activity in the P1 fraction of the kindled group increased significantly only in the left hippocampus (by 49%, P < 0.005), but not in the right hippocampus. Neither PKC activity in the P2 fraction nor that in the cytosolic fraction was altered in the kindled group after this Seizure-free interval.(ABSTRACT TRUNCATED AT 250 WORDS)

  • Ionotropic excitatory amino acid receptors in discrete brain regions of kindled rats.
    Brain research, 1992
    Co-Authors: Kazufumi Akiyama, Ichiro Kohira, Akihiro Daigen, Yukio Yoneda, Kiyokazu Ogita, Takashi Itoh, Ichiro Sora, Hiroshi Ujike, Saburo Otsuki
    Abstract:

    Abstract A study was performed to examine the specific binding of excitatory amino acid (EAA) receptor subtypes in 5 brain regions of rats kindled from the amygdala or hippocampus, using extensively washed and Triton X-100-treated membranes. Seven days after the last amygdala kindled Seizure, [ 3 H](+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine maleate ([ 3 H]MK-801) binding, which labels N- methyl- D -aspartate (NMDA)-sensitive receptor-linked cation channels, decreased significantly only in the amygdala of kindled rats compared to that of controls under equilibrium assay conditions. There was no significant change in [ 3 H]MK-801 binding in the amygdala or hippocampus 7 days after the last hippocampal kindled Seizure, or 28 days after the last amygdala kindled Seizure. Nor was there a significant change in NMDA-sensitive [ 3 H]glutamate, strychnine-insensitive [ 3 H]glycine, [ 3 H]spermidine, [ 3 H]kainate or [ 3 H]α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid ([ 3 H]AMPA) binding in any brain region 7 days after the last amygdala kindled Seizure, or in the hippocampus 28 days after the last amygdala kindled Seizure. These results indicate that [ 3 H]MK-801 binding sites labeling NMDA-sensitive receptor-linked cation channels in the amygdala undergo downregulation only transiently, but that none of the subcomponents of the NMDA receptor macromolecular complex exhibit enduring changes at steady state following the completion of amygdala kindling.

Li Yan - One of the best experts on this subject based on the ideXlab platform.

  • The Expression of Neuropeptide Ghrelin in Amygdala- kindled Seizure in Rats
    Journal of Ningxia Medical University, 2013
    Co-Authors: Li Yan
    Abstract:

    Objective To observe the expression level of neronpeptide chrelin in blood serum and brain tissue in amygdala- kindled rat after Seizure and to explore its causes and significance. Methods Sixty- four healthy male SD rats were randomly divided into blank control group( n = 8),sham- operated group( n = 8)and amygdala- kindled group( n = 48). No treatment was performed in the blank control group. Implantation of electrodes was performed in the sham- operated group. Implantation of electrodes and eletrophotoluminescence were performed in the amygdala- kindled group to induce amygdala- kindled Seizure modles. Rats in the amygdala- kindled group was divided into 6 sub- groups( n = 8) at different times after kindling( 3,6,12,24,48,and 72 h). Enzyme linked immunosorbent assay,immunohistochemistry staining and real- time quantitative polymerase chain reaction were employed to detect the altered Ghrelin in blood and brain tissue of amygdala- kindled rat after Seizure. Results Compared with sham- operated group,expression level of acylated Ghrelin decreased significantly( P 0. 05) in serum and brain tissue of amgydala- kindled rats after Seizure. The expression of acylated Ghrelin were consistent with trend at each time point in serum and hypothalamus. No significant difference on expression of acylated Ghrelinw was found between the sham- operated group and blank control group( P 0. 05). Conclusion The expression level of acylated Ghrelin in serum could reflect level of acylated Ghrelin in hypothalamus. It could be one of Clinical indicators on diagnose and therapy assessment of epilepsy.