Seizures produced by pilocarpine: Neuropathological sequelae and activity of glutamate decarboxylase in the rat forebrain

Turski, Lechosław; Cavalheiro, Ésper A.; Sieklucka-Dziuba, M; Ikonomidou-Turski, Chrysanthy; Czuczwar, Stanisław J.; Turski, Waldemar A.

doi:10.1016/0006-8993(86)91247-3

Cited by 96 publications

(42 citation statements)

References 54 publications

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“…The myorelaxant effect of AW (another NMDA receptor antagonist) infused into the SNr, suggesting an opposite effect compared with catalepsy, is in line with these results (DeSarro et al, 1985;Turski et al, 1986). Opposite effects on motor activity were also observed after the infusion of glutamatergic agonists, such as kainate or NMDA, which were found to induce motor impairments mainly characterized by a cataleptic state (Pycock and Dawbam, 1980;Turski et al, 1987).…”

Section: Discussionsupporting

confidence: 74%

Evidence for Functional Differences between Entopeduncular Nucleus and Substantia Nigra: Effects of APV (DL‐2‐amino‐5‐phosphonovaleric acid) Microinfusion on Reaction Time Performance in the Rat

Baunez

Amalric

1996

Eur J of Neuroscience

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Overactivity of the excitatory amino acid outputs of the subthalamic nucleus (STN) has recently been found to be one of the cascade of subsequent disruptions caused by nigrostriatal dopaminergic degeneration in Parkinson's disease. The respective contribution of the excitatory glutamatergic output structures of the STN [i.e. the globus pallidus (GP), entopeduncular nucleus (EP) and substantia nigra pars reticulata (SNr)] to the control of movement is not known, however. To investigate further the function of glutamatergic transmission through NMDA receptor subtypes in these three structures, the effects of discrete local infusion of a competitive receptor antagonist, DL-2-amino-5-phosphonovaleric acid (APV), into the EP, GP and SNr were tested in rats performing a reaction time task. Bilateral infusion of APV into the different output structures of the STN differentially impaired the performance of rats trained to release a lever after the onset of a visual stimulus within a time limit to obtain a food reward. Infusion of APV (0.25 and 0.5 microgram/0.5 microliter) into the SNr was found to induce behavioural deficits characterized by a dramatic increase in the number of premature lever releases and decreased mean reaction time. In contrast, the infusion of APV at a dose of 0.25 microgram into the GP or EP was found to induce a motor initiation deficit characterized by an increased number of delayed responses (lever release after the time limit) and increased mean reaction time. At a dose of 0.5 microgram, a premature responding deficit was added to the previous motor impairment. Interestingly, when APV was infused simultaneously into the GP and SNr in the same animals, the behavioural effects tended to be similar to those observed after a single infusion into the SNr. Altogether, these results reveal that the different functional weight of the three main output pathways originating at the STN level is t.o. The behavioural deficits induced by NMDA receptor blockade in the SNr were similar to those observed previously after a neurotoxic lesion of the STN, suggesting that NMDA receptors in this structure play a major role as a functional output of the STN. Furthermore, regarding the differential effects produced by the same dose of APV in the SNr and the EP, these two structures, which are classically believed to be functionally linked should not be considered as the same functional entity in the organization of basal ganglia outflow.

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Section: Discussionsupporting

confidence: 74%

Evidence for Functional Differences between Entopeduncular Nucleus and Substantia Nigra: Effects of APV (DL‐2‐amino‐5‐phosphonovaleric acid) Microinfusion on Reaction Time Performance in the Rat

Baunez

Amalric

1996

Eur J of Neuroscience

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“…Systemic administration of pilocarpine progresses from staring spells, limbic gustatory automatisms, and motor limbic seizures that progressively developed into limbic status epilepticus that last for several hours. Pilocarpine-induced status epilepticus causes massive neuronal damage when examined at 24 to 72 hours (Turski et al, 1984(Turski et al, , 1986. In the pilocarpine epileptic animal model, pretreatment with atropine has been shown to normalize pilocarpine-induced temporal lobe epilepsy as well as neuronal death (Jope et al, 1986;Morrisett et al, 1987;Curia et al, 2008).…”

mentioning

confidence: 99%

Rapid Throughput Analysis Demonstrates that Chemicals with Distinct Seizurogenic Mechanisms Differentially Alter Ca²⁺ Dynamics in Networks Formed by Hippocampal Neurons in Culture

et al. 2015

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Primary cultured hippocampal neurons (HN) form functional networks displaying synchronous Ca 21 oscillations (SCOs) whose patterns influence plasticity. Whether chemicals with distinct seizurogenic mechanisms differentially alter SCO patterns was investigated using mouse HN loaded with the Ca 21 indicator fluo-4-AM. Intracellular Ca 21 dynamics were recorded from 96 wells simultaneously in real-time using fluorescent imaging plate reader.

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“…These findings form an interesting parallel to electrical-stimulation studies that indicated a possible role for the caudate nucleus in the control of convulsive activity in the amygdala, hippocampus, and temporal cortex in cats and dogs (21) argues against a preferential role for the SN in gating the expression of seizure activity. The SN and EP both undergo irreversible degeneration in rats subjected to status epilepticus, whereas striatum is resistant to epilepsy-related cell damage (9,22). Similarly, the caudate-putamen is remarkably resistant to the generation of kindled seizures (18).…”

Section: Discussionmentioning

confidence: 99%

Paradoxical anticonvulsant activity of the excitatory amino acid N-methyl-D-aspartate in the rat caudate-putamen.

Turski¹,

Meldrum²,

Cavalheiro³

et al. 1987

Proc. Natl. Acad. Sci. U.S.A.

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We used limbic seizures induced in rats by systemic injection of the cholinergic agonist pilocarpine (380 mg/kg; i.p.) to study the neuronal pathways within the basal ganglia that modulate seizure threshold. N-Methyl-D-aspartate (N-Me-D-Asp) is an excitatory amino acid derivative that is a powerful convulsant agent when injected into the cerebral cortex, amygdala, or hippocampus in rats. Bilateral microinjections of N-Me-D-Asp into the caudate-putamen, however, protected against limbic seizures induced by pilocarpine (injected systemically), with an ED50 of 0.7 nmol (range 0.5-1.0 nmol). Lesioning the caudate-putamen (by bilateral microinjection of the excitotoxin ibotenate) converted subconvulsant doses of pilocarpine into convulsant ones. The anticonvulsant action of N-Me-D-Asp in the caudate-putamen was reversed by blocking y-aminobutyrate-mediated inhibition in the substantia nigra pars reticulata or in the entopeduncular nucleus. The results suggest that the caudate-putamen and its y-aminobutyrate-dependent efferent pathways modulate the threshold for seizures in the limbic forebrain.The function of the basal ganglia in the spread of seizures within the forebrain has interested neurologists, neurosurgeons, and neuropathologists since the 19th century (1). Clinical observations in humans and lesion studies in monkeys and dogs established that the globus pallidus (GP) and the substantia nigra (SN) serve as relay stations in the propagation of seizures elicited from the motor cortex or the limbic system (2, 3). However, the precise pathways in the basal ganglia that are involved in the spread of seizures and the specific neurotransmitters used in these pathways have not been identified.The SN has been proposed as a key site at which the anticonvulsant activity of drugs that enhance y-aminobutyric acid (GABA)-mediated inhibition is expressed (4, 5). Excitation within the SN is probably mediated by dicarboxylic amino acids (L-glutamate or L-aspartate). Blockade of excitatory neurotransmission in the SN by 2-amino-7-phosphonoheptanoate, an antagonist that acts selectively at the receptor site sensitive to N-methyl-D-aspartate (N-Me-D-Asp), raises the threshold for seizures and curtails their motor expression (6, 7).Temporal lobe, or "psychomotor," epilepsy is the most common form of epilepsy in humans (8). Prolonged limbic seizures in animals and humans result in selective damage to the forebrain, involving hippocampus, amygdala, and sometimes the thalamus (9). This form of epilepsy is particularly resistant to anticonvulsant medication and represents a major therapeutic problem (10).Seizures produced by pilocarpine in rats provide an animal model of temporal lobe epilepsy that permits the evaluation of behavioral, electroencephalographic, and morphological sequelae of intractable limbic convulsions (11-13). This experimental model of epilepsy serves to delineate the anatomical substrates essential for the motor expression of seizures (7,14).We recently observed that microinjections of the GABA agonist mu...

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Seizures produced by pilocarpine: Neuropathological sequelae and activity of glutamate decarboxylase in the rat forebrain

Cited by 96 publications

References 54 publications

Evidence for Functional Differences between Entopeduncular Nucleus and Substantia Nigra: Effects of APV (DL‐2‐amino‐5‐phosphonovaleric acid) Microinfusion on Reaction Time Performance in the Rat

Evidence for Functional Differences between Entopeduncular Nucleus and Substantia Nigra: Effects of APV (DL‐2‐amino‐5‐phosphonovaleric acid) Microinfusion on Reaction Time Performance in the Rat

Rapid Throughput Analysis Demonstrates that Chemicals with Distinct Seizurogenic Mechanisms Differentially Alter Ca²⁺ Dynamics in Networks Formed by Hippocampal Neurons in Culture

Paradoxical anticonvulsant activity of the excitatory amino acid N-methyl-D-aspartate in the rat caudate-putamen.

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Seizures produced by pilocarpine: Neuropathological sequelae and activity of glutamate decarboxylase in the rat forebrain

Cited by 96 publications

References 54 publications

Evidence for Functional Differences between Entopeduncular Nucleus and Substantia Nigra: Effects of APV (DL‐2‐amino‐5‐phosphonovaleric acid) Microinfusion on Reaction Time Performance in the Rat

Evidence for Functional Differences between Entopeduncular Nucleus and Substantia Nigra: Effects of APV (DL‐2‐amino‐5‐phosphonovaleric acid) Microinfusion on Reaction Time Performance in the Rat

Rapid Throughput Analysis Demonstrates that Chemicals with Distinct Seizurogenic Mechanisms Differentially Alter Ca2+ Dynamics in Networks Formed by Hippocampal Neurons in Culture

Paradoxical anticonvulsant activity of the excitatory amino acid N-methyl-D-aspartate in the rat caudate-putamen.

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Rapid Throughput Analysis Demonstrates that Chemicals with Distinct Seizurogenic Mechanisms Differentially Alter Ca²⁺ Dynamics in Networks Formed by Hippocampal Neurons in Culture