The Experts below are selected from a list of 249 Experts worldwide ranked by ideXlab platform
Thomas J. Mccown - One of the best experts on this subject based on the ideXlab platform.
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Opposing Actions of Hippocampus TNFα Receptors on Limbic Seizure Susceptibility
Experimental neurology, 2013Co-Authors: Marc S. Weinberg, Bonita L. Blake, Thomas J. MccownAbstract:Abstract Resected epileptic tissues exhibit elements of chronic neuroinflammation that include elevated TNFα and increased TNFα receptor activation, but the Seizure related consequences of chronic TNFα expression remain unknown. Twenty four hours after acute Limbic Seizures the rat hippocampus exhibited a rapid upregulation of TNFR1, but a simultaneous downregulation of TNFR2. These Limbic Seizures also evoked significant increases in measures of neuroinflammation and caused significant neuronal cell death in both the hilus and CA3 of the hippocampus. In order to mimic a state of chronic TNFα exposure, adeno-associated viral vectors were packaged with a TNF receptor 1 (TNFR1) specific agonist, human TNFα, or a TNF receptor 1/2 agonist, rat TNFα. Subsequently, chronic hippocampal overexpression of either TNFR ligand caused microglial activation and blood–brain barrier compromise, a pattern similar to Limbic Seizure-induced neuroinflammation. However, no evidence was found for neuronal cell death or spontaneous Seizure activity. Thus, chronic, in vivo TNFα expression and the subsequent neuroinflammation alone did not cause cell death or elicit Seizure activity. In contrast, chronic hippocampal activation of TNFR1 alone significantly increased Limbic Seizure sensitivity in both amygdala kainic acid and electrical amygdala kindling models, while chronic activation of both TNFR1 and TNFR2 significantly attenuated the amygdala kindling rate. With regard to endogenous TNFα, chronic hippocampal expression of a TNFα decoy receptor significantly reduced Seizure-induced cell death in the hippocampus, but did not alter Seizure susceptibility. These findings suggest that blockade of endogenous TNFα could attenuate Seizure related neuropathology, while selective activation of TNFR2 could exert beneficial therapeutic effects on in vivo Seizure sensitivity.
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adeno associated virus vector mediated expression and constitutive secretion of galanin suppresses Limbic Seizure activity
Neurotherapeutics, 2009Co-Authors: Thomas J. MccownAbstract:Theoretically, gene therapy techniques offer an attractive alternative treatment option for intractable, focal epilepsies. Although logical gene therapy targets include excitatory and inhibitory receptors, variable viral vector tropism interjects an uncertainty as to the direction of change, Seizure suppression, or Seizure sensitization. To circumvent this therapeutic liability, adeno-associated virus (AAV) vectors have been constructed where the gene product is constitutively secreted from the transduced cell. Using AAV vectors, the fibronectin secretory signal sequence (FIB) was placed in front of the coding sequence for green fluorescent protein or the active portion of the neuroactive peptide galanin (GAL). Subsequent studies showed that these vectors supported expression and constitutive secretion of these gene products from transfected cells in vitro. More importantly, upon transduction in vivo, AAV-FIB-GAL vectors significantly attenuated focal Seizure sensitivity, and this Seizure attenuation could be controlled in vivo by using a tetracyclineregulated promoter. The expression and constitutive secretion of green fluorescent protein, or the expression of GAL alone, exerted no effect on focal Seizure sensitivity. Moreover, unilateral infusion of the AAV-FIB-GAL vectors into the hippocampus prevented kainic acid-induced hilar cell death. With regard to Limbic Seizures, bilateral infusion of AAV-FIB-GAL vectors into the piriform cortex prevented both behavioral and localized electrographic Seizure activity after the peripheral administration of kainic acid. Also, when rats were electrically kindled to class V Seizure activity, subsequent infusion of AAV-FIB-GAL proved capable of significantly elevating the Seizure initiation threshold. Thus, these studies clearly demonstrate the anti-Seizure effectiveness of AAV vector-mediated expression and constitutive secretion of galanin.
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Adeno-associated virus-mediated expression and constitutive secretion of NPY or NPY13-36 suppresses Seizure activity in vivo
Gene Therapy, 2007Co-Authors: S Foti, R P Haberman, R J Samulski, Thomas J. MccownAbstract:Neuropeptide Y (NPY) is a 36-amino-acid peptide that attenuates Seizure activity following direct infusion or adeno-associated virus (AAV)-mediated expression in the central nervous system. However, NPY activates all NPY receptor subtypes, potentially causing unwanted side effects. NPY13-36 is a C-terminal peptide fragment of NPY that primarily activates the NPY Y2 receptor, thought to mediate the antiSeizure activity. Therefore, we investigated if recombinant adeno-associated virus-mediated expression and constitutive secretion of NPY or NPY13-36 could alter Limbic Seizure sensitivity. Rats received bilateral piriform cortex infusions of AAV vectors that express and constitutively secrete full-length NPY (AAV-FIB-NPY) or NPY13-36 (AAV-FIB-NPY13-36). Control rats received no infusion, as we have previously shown that vectors expressing and secreting reporter genes like GFP (AAV-FIB-EGFP), as well as vectors expressing peptides that lack secretion sequences (AAV-GAL) have no effect on Seizures. One week later, all animals received kainic acid (10 mg kg^−1, intraperitoneally), and the latencies to wet dog shakes and Limbic Seizure behaviors were determined. Although both control and vector-treated rats developed wet dog shake behaviors with similar latencies, the latencies to class III and class IV Limbic Seizures were significantly prolonged in both NPY- and NPY13-36-treated groups. Thus, AAV-mediated expression and constitutive secretion of NPY and NPY13-36 is effective in attenuating Limbic Seizures, and provides a platform for delivering therapeutic peptide fragments with increased receptor selectivity.
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Adeno-associated virus-mediated expression and constitutive secretion of galanin suppresses Limbic Seizure activity in vivo.
Molecular therapy : the journal of the American Society of Gene Therapy, 2006Co-Authors: Thomas J. MccownAbstract:Intractable temporal lobe epilepsy presents an ideal target for gene therapy, but therapeutic success depends upon the ability to suppress Limbic Seizure activity. Adeno-associated virus vectors (AAV) were constructed in which the fibronectin secretory signal sequence (FIB) preceded the coding sequence for galanin (AAV-FIB-GAL) or green fluorescent protein (AAV-FIB-GFP), constructs that express and constitutively secrete the gene product. Bilateral AAV-FIB-GAL infusion into the rat piriform cortex (2 μl/side) significantly attenuated kainic acid-induced Seizures (10 mg/kg, ip) such that 11/12 rats exhibited no Limbic Seizures, while the remaining rat exhibited only a brief, single class III Seizure. This AAV-FIB-GAL infusion also prevented electrographic Seizure activity. In contrast, bilateral AAV-FIB-GFP infusion did not alter either behavioral or electrographic Seizure activity. Since prior Seizure exposure could influence vector efficacy, another group of rats received daily electrical stimulation of the piriform cortex until three consecutive class V Seizures were elicited. Subsequently, AAV-FIB-GAL or AAV-FIB-GFP (3 μl/30 min) was infused into the area of the electrode. One week later the AAV-FIB-GAL rats exhibited a significant increase in the stimulation current necessary to evoke Limbic Seizure activity, while AAV-FIB-GFP did not alter the Seizure threshold. Thus, AAV-mediated galanin expression and secretion significantly suppress Limbic Seizure activity in vivo.
Marina Bentivoglio - One of the best experts on this subject based on the ideXlab platform.
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different patterns of neuronal activation and neurodegeneration in the thalamus and cortex of epilepsy resistant proechimys rats versus wistar rats after pilocarpine induced protracted Seizures
Epilepsia, 2009Co-Authors: Anna Andrioli, Esper A. Cavalheiro, Paolo F. Fabene, Roberto Spreafico, Marina BentivoglioAbstract:Summary Purpose: To analyze cellular mechanisms of Limbic-Seizure suppression, the response to pilocarpine-induced Seizures was investigated in cortex and thalamus, comparing epilepsy-resistant rats Proechimys guyannensis with Wistar rats. Methods: Fos immunoreactivity revealing neuronal activation, and degenerating neurons labeled by Fluoro-Jade B (FJB) histochemistry were analyzed on the first day after onset of Seizures lasting 3 h. Subpopulations of γ-aminobutyric acid (GABA)ergic cells were characterized with double Fos-parvalbumin immunohistochemistry. Results: In both cortex and thalamus, degenerating neurons were much fewer in Proechimys than Wistar rats. Fos persisted at high levels at 24 h only in the Proechimys thalamus and cortex, especially in layer VI where corticothalamic neurons reside. In the parietal cortex, about 50% of parvalbumin-containing interneurons at 8 h, and 10–20% at 24 h, were Fos-positive in Wistar rats, but in Proechimys, Fos was expressed in almost all parvalbumin-containing interneurons at 8 h and dropped at 24 h. Fos positivity in cingulate cortex interneurons was similar in both species. In the Wistar rat thalamus, Fos was induced in medial and midline nuclei up to 8 h, when <30% of reticular nucleus cells were Fos-positive, and then decreased, with no relationship with cell loss, evaluated in Nissl-stained sections. In Proechimys, almost all reticular nucleus neurons were Fos-positive at 24 h. Discussion: At variance with laboratory rats, pilocarpine-induced protracted Seizures elicit in Proechimys limited neuronal death, and marked and long-lasting Fos induction in excitatory and inhibitory cortical and thalamic cell subsets. The findings implicate intrathalamic and intracortical regulation, and circuits linking thalamus and cortex in Limbic Seizure suppression leading to epilepsy resistance.
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Different patterns of neuronal activation and neurodegeneration in the thalamus and cortex of epilepsy-resistant Proechimys rats versus Wistar rats after pilocarpine-induced protracted Seizures.
Epilepsia, 2009Co-Authors: Anna Andrioli, Esper A. Cavalheiro, Paolo F. Fabene, Roberto Spreafico, Marina BentivoglioAbstract:Summary Purpose: To analyze cellular mechanisms of Limbic-Seizure suppression, the response to pilocarpine-induced Seizures was investigated in cortex and thalamus, comparing epilepsy-resistant rats Proechimys guyannensis with Wistar rats. Methods: Fos immunoreactivity revealing neuronal activation, and degenerating neurons labeled by Fluoro-Jade B (FJB) histochemistry were analyzed on the first day after onset of Seizures lasting 3 h. Subpopulations of γ-aminobutyric acid (GABA)ergic cells were characterized with double Fos-parvalbumin immunohistochemistry. Results: In both cortex and thalamus, degenerating neurons were much fewer in Proechimys than Wistar rats. Fos persisted at high levels at 24 h only in the Proechimys thalamus and cortex, especially in layer VI where corticothalamic neurons reside. In the parietal cortex, about 50% of parvalbumin-containing interneurons at 8 h, and 10–20% at 24 h, were Fos-positive in Wistar rats, but in Proechimys, Fos was expressed in almost all parvalbumin-containing interneurons at 8 h and dropped at 24 h. Fos positivity in cingulate cortex interneurons was similar in both species. In the Wistar rat thalamus, Fos was induced in medial and midline nuclei up to 8 h, when
Edward H Bertram - One of the best experts on this subject based on the ideXlab platform.
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suppressing Limbic Seizures by stimulating medial dorsal thalamic nucleus factors for efficacy
Epilepsia, 2015Co-Authors: Dexing Zhang, Edward H BertramAbstract:Summary Objective The optimal sites and stimulation protocols for brain stimulation in epilepsy have not been found. Clinical trials, which have shown modest benefit in Seizure reduction, have involved patients with poorly localized intractable focal epilepsy and stimulation sites without clear relations to specific underlying Seizure circuits. The medial dorsal thalamic nucleus is a key node in Limbic Seizure circuits, and we wished to know what stimulation parameters might control Seizures in a kindling model of Limbic epilepsy. Methods In urethane-anesthetized rats, we induced Limbic Seizures by stimulation of the piriform cortex or CA3 of the hippocampus while recording in the entorhinal cortex or CA1 of the contralateral hippocampus to determine the effect of specific stimulation parameters on Seizure duration. Results Stimulation consistently suppressed Seizure duration from baseline by over 80% (p < 0.001), frequently completely preventing the Seizures. Position of the thalamic electrode, stimulus intensity and frequency had a significant influence, with higher stimulus intensities (40 V vs. 20 V) and frequencies (20 Hz vs. 7 Hz) significantly suppressing Seizures. The most effective position was the lateral dorsal area of the medial dorsal nucleus (MD), which corresponded to the region of axon entry. Stimulation in the MD center was not effective. An anterior-posterior relationship of the stimulating electrode pair was effective, whereas a medial lateral orientation was not. Successful stimulation suppressed the evoked responses in the entorhinal cortex or CA1. Significance Position and orientation of the stimulating electrode has to be precise, which suggests that the placement of the electrodes must be tailored to the individual's own Seizure circuit. The data also indicate that successful deep brain stimulation induces a fundamental change in system physiology, which could be a marker to guide the development of stimulation parameters for each patient.
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Suppressing Limbic Seizures by stimulating medial dorsal thalamic nucleus: Factors for efficacy
Epilepsia, 2015Co-Authors: Dexing Zhang, Edward H BertramAbstract:Summary Objective The optimal sites and stimulation protocols for brain stimulation in epilepsy have not been found. Clinical trials, which have shown modest benefit in Seizure reduction, have involved patients with poorly localized intractable focal epilepsy and stimulation sites without clear relations to specific underlying Seizure circuits. The medial dorsal thalamic nucleus is a key node in Limbic Seizure circuits, and we wished to know what stimulation parameters might control Seizures in a kindling model of Limbic epilepsy. Methods In urethane-anesthetized rats, we induced Limbic Seizures by stimulation of the piriform cortex or CA3 of the hippocampus while recording in the entorhinal cortex or CA1 of the contralateral hippocampus to determine the effect of specific stimulation parameters on Seizure duration. Results Stimulation consistently suppressed Seizure duration from baseline by over 80% (p
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FULL-LENGTH ORIGINAL RESEARCH Multiple roles of midline dorsal thalamic nuclei in induction and spread of Limbic Seizures
2008Co-Authors: Edward H Bertram, Dexing Zhang, John WilliamsonAbstract:SUMMARY Purpose: Studies have suggested that the medial dorsal nucleus of the thalamus plays a role in the behavioral expression of Limbic Seizures, but it is unclear whether this region is a key component for the primary Seizure circuitry or a path for Seizure spread from one region to another. This study was undertaken to determine the potential role of this region in Limbic Seizure activity. Methods: Adult male rats received kindling stimulation either under urethane anesthesia or while awake. Glutamate or its agonists or the GABA antagonist bicuculline or agonist muscimol were infused into the medial dorsal nucleus. In another series, kindling acquisition was compared among three thalamic sites as well as with the amygdala and hippocampus Results: Drugs that enhanced excitatory drive or blocked GABA resulted in significant prolongation of electrographic Seizure activity compared to saline infused controls. Enhanced GABA activity resulted in a significant reduction of Seizure duration. Infusion of the compounds lateral to the medial dorsal nucleus did not affect Seizure duration. In the kindling studies the medial dorsal region is the only thalamic nucleus from which hippocampal Seizures can be induced, but with an elevated afterdischarge threshold compared to the two Limbic sites. However, the Seizures generalized more rapidly from the medial dorsal region. Conclusions: This study demonstrates that the medial dorsal nucleus and other dorsal midline nuclei have a significant role in the primary Seizure circuits of Limbic Seizures as well as in spread of Seizure activity to other regions.
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Multiple roles of midline dorsal thalamic nuclei in induction and spread of Limbic Seizures
Epilepsia, 2007Co-Authors: Edward H Bertram, Dexing Zhang, John WilliamsonAbstract:PURPOSE: Studies have suggested that the medial dorsal nucleus of the thalamus plays a role in the behavioral expression of Limbic Seizures, but it is unclear whether this region is a key component for the primary Seizure circuitry or a path for Seizure spread from one region to another. This study was undertaken to determine the potential role of this region in Limbic Seizure activity. METHODS: Adult male rats received kindling stimulation either under urethane anesthesia or while awake. Glutamate or its agonists or the GABA antagonist bicuculline or agonist muscimol were infused into the medial dorsal nucleus. In another series, kindling acquisition was compared among three thalamic sites as well as with the amygdala and hippocampus RESULTS: Drugs that enhanced excitatory drive or blocked GABA resulted in significant prolongation of electrographic Seizure activity compared to saline infused controls. Enhanced GABA activity resulted in a significant reduction of Seizure duration. Infusion of the compounds lateral to the medial dorsal nucleus did not affect Seizure duration. In the kindling studies the medial dorsal region is the only thalamic nucleus from which hippocampal Seizures can be induced, but with an elevated afterdischarge threshold compared to the two Limbic sites. However, the Seizures generalized more rapidly from the medial dorsal region. CONCLUSIONS: This study demonstrates that the medial dorsal nucleus and other dorsal midline nuclei have a significant role in the primary Seizure circuits of Limbic Seizures as well as in spread of Seizure activity to other regions.
Anna Andrioli - One of the best experts on this subject based on the ideXlab platform.
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different patterns of neuronal activation and neurodegeneration in the thalamus and cortex of epilepsy resistant proechimys rats versus wistar rats after pilocarpine induced protracted Seizures
Epilepsia, 2009Co-Authors: Anna Andrioli, Esper A. Cavalheiro, Paolo F. Fabene, Roberto Spreafico, Marina BentivoglioAbstract:Summary Purpose: To analyze cellular mechanisms of Limbic-Seizure suppression, the response to pilocarpine-induced Seizures was investigated in cortex and thalamus, comparing epilepsy-resistant rats Proechimys guyannensis with Wistar rats. Methods: Fos immunoreactivity revealing neuronal activation, and degenerating neurons labeled by Fluoro-Jade B (FJB) histochemistry were analyzed on the first day after onset of Seizures lasting 3 h. Subpopulations of γ-aminobutyric acid (GABA)ergic cells were characterized with double Fos-parvalbumin immunohistochemistry. Results: In both cortex and thalamus, degenerating neurons were much fewer in Proechimys than Wistar rats. Fos persisted at high levels at 24 h only in the Proechimys thalamus and cortex, especially in layer VI where corticothalamic neurons reside. In the parietal cortex, about 50% of parvalbumin-containing interneurons at 8 h, and 10–20% at 24 h, were Fos-positive in Wistar rats, but in Proechimys, Fos was expressed in almost all parvalbumin-containing interneurons at 8 h and dropped at 24 h. Fos positivity in cingulate cortex interneurons was similar in both species. In the Wistar rat thalamus, Fos was induced in medial and midline nuclei up to 8 h, when <30% of reticular nucleus cells were Fos-positive, and then decreased, with no relationship with cell loss, evaluated in Nissl-stained sections. In Proechimys, almost all reticular nucleus neurons were Fos-positive at 24 h. Discussion: At variance with laboratory rats, pilocarpine-induced protracted Seizures elicit in Proechimys limited neuronal death, and marked and long-lasting Fos induction in excitatory and inhibitory cortical and thalamic cell subsets. The findings implicate intrathalamic and intracortical regulation, and circuits linking thalamus and cortex in Limbic Seizure suppression leading to epilepsy resistance.
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Different patterns of neuronal activation and neurodegeneration in the thalamus and cortex of epilepsy-resistant Proechimys rats versus Wistar rats after pilocarpine-induced protracted Seizures.
Epilepsia, 2009Co-Authors: Anna Andrioli, Esper A. Cavalheiro, Paolo F. Fabene, Roberto Spreafico, Marina BentivoglioAbstract:Summary Purpose: To analyze cellular mechanisms of Limbic-Seizure suppression, the response to pilocarpine-induced Seizures was investigated in cortex and thalamus, comparing epilepsy-resistant rats Proechimys guyannensis with Wistar rats. Methods: Fos immunoreactivity revealing neuronal activation, and degenerating neurons labeled by Fluoro-Jade B (FJB) histochemistry were analyzed on the first day after onset of Seizures lasting 3 h. Subpopulations of γ-aminobutyric acid (GABA)ergic cells were characterized with double Fos-parvalbumin immunohistochemistry. Results: In both cortex and thalamus, degenerating neurons were much fewer in Proechimys than Wistar rats. Fos persisted at high levels at 24 h only in the Proechimys thalamus and cortex, especially in layer VI where corticothalamic neurons reside. In the parietal cortex, about 50% of parvalbumin-containing interneurons at 8 h, and 10–20% at 24 h, were Fos-positive in Wistar rats, but in Proechimys, Fos was expressed in almost all parvalbumin-containing interneurons at 8 h and dropped at 24 h. Fos positivity in cingulate cortex interneurons was similar in both species. In the Wistar rat thalamus, Fos was induced in medial and midline nuclei up to 8 h, when
Dexing Zhang - One of the best experts on this subject based on the ideXlab platform.
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suppressing Limbic Seizures by stimulating medial dorsal thalamic nucleus factors for efficacy
Epilepsia, 2015Co-Authors: Dexing Zhang, Edward H BertramAbstract:Summary Objective The optimal sites and stimulation protocols for brain stimulation in epilepsy have not been found. Clinical trials, which have shown modest benefit in Seizure reduction, have involved patients with poorly localized intractable focal epilepsy and stimulation sites without clear relations to specific underlying Seizure circuits. The medial dorsal thalamic nucleus is a key node in Limbic Seizure circuits, and we wished to know what stimulation parameters might control Seizures in a kindling model of Limbic epilepsy. Methods In urethane-anesthetized rats, we induced Limbic Seizures by stimulation of the piriform cortex or CA3 of the hippocampus while recording in the entorhinal cortex or CA1 of the contralateral hippocampus to determine the effect of specific stimulation parameters on Seizure duration. Results Stimulation consistently suppressed Seizure duration from baseline by over 80% (p < 0.001), frequently completely preventing the Seizures. Position of the thalamic electrode, stimulus intensity and frequency had a significant influence, with higher stimulus intensities (40 V vs. 20 V) and frequencies (20 Hz vs. 7 Hz) significantly suppressing Seizures. The most effective position was the lateral dorsal area of the medial dorsal nucleus (MD), which corresponded to the region of axon entry. Stimulation in the MD center was not effective. An anterior-posterior relationship of the stimulating electrode pair was effective, whereas a medial lateral orientation was not. Successful stimulation suppressed the evoked responses in the entorhinal cortex or CA1. Significance Position and orientation of the stimulating electrode has to be precise, which suggests that the placement of the electrodes must be tailored to the individual's own Seizure circuit. The data also indicate that successful deep brain stimulation induces a fundamental change in system physiology, which could be a marker to guide the development of stimulation parameters for each patient.
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Suppressing Limbic Seizures by stimulating medial dorsal thalamic nucleus: Factors for efficacy
Epilepsia, 2015Co-Authors: Dexing Zhang, Edward H BertramAbstract:Summary Objective The optimal sites and stimulation protocols for brain stimulation in epilepsy have not been found. Clinical trials, which have shown modest benefit in Seizure reduction, have involved patients with poorly localized intractable focal epilepsy and stimulation sites without clear relations to specific underlying Seizure circuits. The medial dorsal thalamic nucleus is a key node in Limbic Seizure circuits, and we wished to know what stimulation parameters might control Seizures in a kindling model of Limbic epilepsy. Methods In urethane-anesthetized rats, we induced Limbic Seizures by stimulation of the piriform cortex or CA3 of the hippocampus while recording in the entorhinal cortex or CA1 of the contralateral hippocampus to determine the effect of specific stimulation parameters on Seizure duration. Results Stimulation consistently suppressed Seizure duration from baseline by over 80% (p
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FULL-LENGTH ORIGINAL RESEARCH Multiple roles of midline dorsal thalamic nuclei in induction and spread of Limbic Seizures
2008Co-Authors: Edward H Bertram, Dexing Zhang, John WilliamsonAbstract:SUMMARY Purpose: Studies have suggested that the medial dorsal nucleus of the thalamus plays a role in the behavioral expression of Limbic Seizures, but it is unclear whether this region is a key component for the primary Seizure circuitry or a path for Seizure spread from one region to another. This study was undertaken to determine the potential role of this region in Limbic Seizure activity. Methods: Adult male rats received kindling stimulation either under urethane anesthesia or while awake. Glutamate or its agonists or the GABA antagonist bicuculline or agonist muscimol were infused into the medial dorsal nucleus. In another series, kindling acquisition was compared among three thalamic sites as well as with the amygdala and hippocampus Results: Drugs that enhanced excitatory drive or blocked GABA resulted in significant prolongation of electrographic Seizure activity compared to saline infused controls. Enhanced GABA activity resulted in a significant reduction of Seizure duration. Infusion of the compounds lateral to the medial dorsal nucleus did not affect Seizure duration. In the kindling studies the medial dorsal region is the only thalamic nucleus from which hippocampal Seizures can be induced, but with an elevated afterdischarge threshold compared to the two Limbic sites. However, the Seizures generalized more rapidly from the medial dorsal region. Conclusions: This study demonstrates that the medial dorsal nucleus and other dorsal midline nuclei have a significant role in the primary Seizure circuits of Limbic Seizures as well as in spread of Seizure activity to other regions.
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Multiple roles of midline dorsal thalamic nuclei in induction and spread of Limbic Seizures
Epilepsia, 2007Co-Authors: Edward H Bertram, Dexing Zhang, John WilliamsonAbstract:PURPOSE: Studies have suggested that the medial dorsal nucleus of the thalamus plays a role in the behavioral expression of Limbic Seizures, but it is unclear whether this region is a key component for the primary Seizure circuitry or a path for Seizure spread from one region to another. This study was undertaken to determine the potential role of this region in Limbic Seizure activity. METHODS: Adult male rats received kindling stimulation either under urethane anesthesia or while awake. Glutamate or its agonists or the GABA antagonist bicuculline or agonist muscimol were infused into the medial dorsal nucleus. In another series, kindling acquisition was compared among three thalamic sites as well as with the amygdala and hippocampus RESULTS: Drugs that enhanced excitatory drive or blocked GABA resulted in significant prolongation of electrographic Seizure activity compared to saline infused controls. Enhanced GABA activity resulted in a significant reduction of Seizure duration. Infusion of the compounds lateral to the medial dorsal nucleus did not affect Seizure duration. In the kindling studies the medial dorsal region is the only thalamic nucleus from which hippocampal Seizures can be induced, but with an elevated afterdischarge threshold compared to the two Limbic sites. However, the Seizures generalized more rapidly from the medial dorsal region. CONCLUSIONS: This study demonstrates that the medial dorsal nucleus and other dorsal midline nuclei have a significant role in the primary Seizure circuits of Limbic Seizures as well as in spread of Seizure activity to other regions.