Seizures induced by penicillin microinjections in the mesencephalic tegmentum

Jiménez, Fiacro; Velasco, Francisco; Carrillo-Ruíz, José Damián; F, Villanueva; Velasco, Marcos; Ponce, Hector

doi:10.1016/s0920-1211(99)00078-9

Cited by 7 publications

(4 citation statements)

References 29 publications

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“…This suggested that phasic currents would always be inhibited by penicillin, regardless of which subset of receptor isoforms is localized to synapses. Penicillin is therefore likely to have widespread effects on phasic inhibition, which may underlie its potent pro-convulsant properties and ability to produce epileptiform activity in vitro (Schneiderman et al, 1994; Uysal et al, 1996; Schneiderman 1997; Jimenez et al, 2000; Shen and Lai, 2002). …”

Section: Discussionmentioning

confidence: 99%

Context-dependent modulation of αβγ and αβδ GABAA receptors by penicillin: Implications for phasic and tonic inhibition

2009

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SummaryPenicillin, an open-channel blocker of GABA A receptors, was recently reported to inhibit phasic, but not tonic, currents in hippocampal neurons. To distinguish between isoform-specific and contextdependent modulation as possible explanations for this selectivity, the effects of penicillin were evaluated on recombinant GABA A receptors expressed in HEK293T cells. When co-applied with saturating GABA, penicillin decreased peak amplitude, induced rebound, and prolonged deactivation of currents evoked from both synaptic and extrasynaptic receptor isoforms. However, penicillin had isoform-specific effects on the extent of desensitization, reflecting its ability to differentially modulate peak (non-equilibrium) and residual (near-equilibrium) currents. This suggested that the context of activation could determine the apparent sensitivity of a given receptor isoform to penicillin. To test this hypothesis, we explored the ability of penicillin to modulate synaptic and extrasynaptic isoforms that were activated under more physiologically relevant conditions. Interestingly, while currents evoked from synaptic isoforms under phasic conditions (transient activation by a saturating concentration of GABA) were substantially inhibited by penicillin, currents evoked from extrasynaptic isoforms under tonic conditions (prolonged application by a sub-saturating concentration of GABA) were minimally affected. We therefore concluded that the reported inability of penicillin to modulate tonic currents could not simply be attributed to insensitivity of extrasynaptic receptors, but rather, reflected an inability to modulate these receptors in their native context of activation.

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Section: Discussionmentioning

confidence: 99%

Context-dependent modulation of αβγ and αβδ GABAA receptors by penicillin: Implications for phasic and tonic inhibition

2009

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“…For example, severe and treatment-resistant epileptic seizures appeared in a patient after the unintentional administration of a high dose of mezlocillin in a brain ventricle (1). In another report Marangoz and Bagirici applied 3 3 10 6 units of penicillin G per kilogram of body weight to provoke epileptic activity in rats, whereas Jimenez et al stereotaxically administered 250 to 500 units of penicillin into multiple brain structures and registered motor and electroencephalographic seizures in awakened cats (25,26). Jin et al lowered the PTZ convulsive threshold in rodents by intravenously administering 800 mg/kg body wt cefazolin but not by intravenously administering 400 mg/kg (27).…”

Section: Effects Of Ceftriaxone On the Latency Times Of Ptz-evoked Convulsion Patterns And Deathmentioning

confidence: 99%

Beneficial Effects of Ceftriaxone Against Pentylenetetrazole-Evoked Convulsions

Jelenković

Jovanović²,

Stanimirovic³

et al. 2008

Exp Biol Med (Maywood)

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Although considered to be generally safe, a number of beta-lactam antibiotics have been associated with epileptic seizures in humans. Furthermore, some beta-lactam antibiotics, including ceftriaxone, are used to evoke convulsions under experimental conditions. Recently it was demonstrated that ceftriaxone increased expression of the glutamate transporter (GLT1) and its biochemical and functional activity in the brain of rodents. GLT1 regulates extracellular concentrations of glutamate, an excitatory amino acid involved in the pathogenesis of seizures and epilepsy. Because of its rapid transfer of glutamate into neurons and adjacent glial cells, GLT1 diminishes glutamate toxicity. We investigated whether ceftriaxone (200 mg/kg body wt) administered intraperitoneally (ip) for 6 days could modify the convulsant effects of pentylenetetrazole (PTZ, 100 mg/kg ip) in inbred male BALBcAnNCR and C57 black (BL)/6 mice aged 4 and 12 weeks. Ceftriaxone pretreatment provided significant protective effects against PTZ-evoked generalized clonic convulsions (GCCs), generalized clonic-tonic convulsions (GCTCs), and convulsion-induced mortality during a period of 30 mins after PTZ administration. The incidence of GCCs, GCTCs, and death was statistically significantly lower for BALBcAnNCR mice of both ages, particularly younger mice. The latency time for each of the three parameters was significantly greater, with the exception of GCCs in adult mice. Protective effects of ceftriaxone were also noticed in adult C57BL/6 mice but not in prepubertal C57BL/6 mice. This is the first demonstration of anticonvulsant effects of ceftriaxone or any other beta-lactam antibiotic, which are not uniform across the mouse population. Our results provide new insight into the effects of ceftriaxone, which need further investigation.

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“…For example, in the experimental model of epilepsy induced by topical injection of penicillin, hundreds of penicillin units are necessary to induce focal seizures when injected in the cerebral cortex, 31 whereas only 10 to 20 units induced focal epileptic attacks when delivered by microinjections in the mesencephalic tegmentum. 32 In the experimental model of generalized seizures induced by intravenous administration of pentylenetetrazol in cats (20 mg/kg), bipolar electrodes with 40-mm tip size were placed in mesencephalic, pontine, and bulbar RF, nucleus centralis medialis of thalamus, and associative cortex as representative of nonspecific areas, and vestibular, facial, and trigeminal nerves nuclei, superior colliculus, lateral geniculate nucleus, and motor cortex as representative of specific brain stem thalamic-cortical structures. Signals were filtered for recording EEG (1-100 Hz) and multiunit activity (MUA) (1,000-10,000 Hz) simultaneously.…”

Section: Epilepsy and The Rf Systemmentioning

confidence: 99%

Section: Functional Backgroundmentioning

confidence: 99%

Centromedian Nucleus and Epilepsy

Velasco

Saucedo-Alvarado

Reichrath

et al. 2021

Journal of Clinical Neurophysiology

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Summary: Centromedian thalamic nucleus is an intralaminar nucleus with vast connectivity to cerebral cortex and basal ganglia. It receives afferents from the brain stem through the central tegmental tract and is part of the diffuse thalamic projection system. Because the reticulothalamic system has been related to initiation and propagation of epileptic activity (centroencephalic theory of epilepsy), deep brain stimulation has been proposed to interfere with seizure genesis or propagation. Centromedian thalamic nucleus is a large nucleus laying nearby the anatomical references for stereotaxis and therefore a convenient surgical target to approach. Electrodes are implanted in the anterior ventral lateral part of the nucleus (parvocellular area), guided by intraoperative recruiting responses elicited by unilateral 6 to 8 Hz electrical stimulation delivered through the deep brain stimulation electrode. Therapeutic stimulation is delivered with the following parameters: 60 Hz, 450 μs, 3.0 V. Seizure control runs between 69% and 83% in different reports, decreasing mainly generalized seizures from the start, with significant improvement in neuropsychological performance. Significant decrease in seizure occurs from hours to days after the onset of deep brain stimulation. Some reports refer that seizure improvement may occur by the simple insertion of the deep brain stimulation electrodes, and therefore, it was used to treat refractory epileptic status.

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Seizures induced by penicillin microinjections in the mesencephalic tegmentum

Cited by 7 publications

References 29 publications

Context-dependent modulation of αβγ and αβδ GABAA receptors by penicillin: Implications for phasic and tonic inhibition

Context-dependent modulation of αβγ and αβδ GABAA receptors by penicillin: Implications for phasic and tonic inhibition

Beneficial Effects of Ceftriaxone Against Pentylenetetrazole-Evoked Convulsions

Centromedian Nucleus and Epilepsy

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