Effect of a Single Brief Seizure on Subsequent Seizure Susceptibility in the Immature Rat

Pentylenetetrazole‐induced seizures cause acute, but not chronic, mTOR pathway activation in rat

“…Although in the kainate and pilocarpine models, a second, chronic phase of mTOR activation occurs over days to weeks following the initial seizures (Zeng et al., 2009; Huang et al., 2010), there is no such secondary, late mTOR activation following PTZ seizures. Because PTZ seizures do not typically lead to neuropathologic injury or spontaneous epilepsy (Holmes et al., 1984; Wong et al., 2003), this suggests that the acute phase of seizure‐induced mTOR activation is not sufficient to trigger epileptogenesis. By comparison, after resolution of the acute seizures in the kainate and pilocarpine models, subsequent inhibition of the later phase of mTOR activation has been implicated in suppressing pathologic changes (Buckmaster et al., 2009) and spontaneous seizures (Zeng et al., 2009; Huang et al., 2010) that develop in these other models.…”

“…Then, a second, more chronic phase of mTOR activation evolves over days to weeks and correlates with the process of epileptogenesis and eventual development of spontaneous seizures. In contrast to the kainate model, pentylenetetrazole (PTZ) is an antagonist of γ‐aminobutyric acid (GABA) receptors that induces acute seizures in rodents, but without repetitive applications of PTZ (kindling), this exposure does not appear to lead to significant pathologic changes or spontaneous epilepsy (Holmes et al., 1984; Wong et al., 2003). Therefore, the PTZ model offers an opportunity to isolate the direct effects of seizures on the mTOR pathway, in the absence of chronic epileptogenesis.…”

Pentylenetetrazole‐induced seizures cause acute, but not chronic, mTOR pathway activation in rat

“…Although in the kainate and pilocarpine models, a second, chronic phase of mTOR activation occurs over days to weeks following the initial seizures (Zeng et al., 2009; Huang et al., 2010), there is no such secondary, late mTOR activation following PTZ seizures. Because PTZ seizures do not typically lead to neuropathologic injury or spontaneous epilepsy (Holmes et al., 1984; Wong et al., 2003), this suggests that the acute phase of seizure‐induced mTOR activation is not sufficient to trigger epileptogenesis. By comparison, after resolution of the acute seizures in the kainate and pilocarpine models, subsequent inhibition of the later phase of mTOR activation has been implicated in suppressing pathologic changes (Buckmaster et al., 2009) and spontaneous seizures (Zeng et al., 2009; Huang et al., 2010) that develop in these other models.…”

“…Then, a second, more chronic phase of mTOR activation evolves over days to weeks and correlates with the process of epileptogenesis and eventual development of spontaneous seizures. In contrast to the kainate model, pentylenetetrazole (PTZ) is an antagonist of γ‐aminobutyric acid (GABA) receptors that induces acute seizures in rodents, but without repetitive applications of PTZ (kindling), this exposure does not appear to lead to significant pathologic changes or spontaneous epilepsy (Holmes et al., 1984; Wong et al., 2003). Therefore, the PTZ model offers an opportunity to isolate the direct effects of seizures on the mTOR pathway, in the absence of chronic epileptogenesis.…”

Do vaccines cause epilepsy? Review of cases in the National Vaccine Injury Compensation Program

“…With the possible exception of FSE, which will be discussed below, there is no scientific evidence to support the contention that single or recurrent febrile seizures cause cell loss, apoptosis, aberrant mossy fiber sprouting, or epilepsy. 65,66 Likewise, animal studies do not show that single 67,68 or repeated afebrile seizures [69][70][71] result in cell loss or epilepsy.…”

mTOR-Related Cell-Clearing Systems in Epileptic Seizures, an Update

“…For instance, pentylenetetrazole (PTZ) is a GABA a receptor antagonist used to induce seizures in experimental settings through decreasing inhibitory GABA activity. PTZ's effect is most prominent in the cortex and hippocampus, and its acute administration is a valuable model of generalized tonic-clonic and myoclonic seizures [107,108], while repetitive administrations of PTZ (kindling) are needed to induce SE and pathological alterations [109,110]. Chemical kindling seizures triggered by PTZ are assumed to mimic the pathogenesis of human epilepsy and are considered a model of drug-resistant epilepsy [109,110].…”

Pentylenetetrazole‐induced seizures cause acute, but not chronic, mTOR pathway activation in rat

“…Although in the kainate and pilocarpine models, a second, chronic phase of mTOR activation occurs over days to weeks following the initial seizures (Zeng et al., 2009; Huang et al., 2010), there is no such secondary, late mTOR activation following PTZ seizures. Because PTZ seizures do not typically lead to neuropathologic injury or spontaneous epilepsy (Holmes et al., 1984; Wong et al., 2003), this suggests that the acute phase of seizure‐induced mTOR activation is not sufficient to trigger epileptogenesis. By comparison, after resolution of the acute seizures in the kainate and pilocarpine models, subsequent inhibition of the later phase of mTOR activation has been implicated in suppressing pathologic changes (Buckmaster et al., 2009) and spontaneous seizures (Zeng et al., 2009; Huang et al., 2010) that develop in these other models.…”

“…Then, a second, more chronic phase of mTOR activation evolves over days to weeks and correlates with the process of epileptogenesis and eventual development of spontaneous seizures. In contrast to the kainate model, pentylenetetrazole (PTZ) is an antagonist of γ‐aminobutyric acid (GABA) receptors that induces acute seizures in rodents, but without repetitive applications of PTZ (kindling), this exposure does not appear to lead to significant pathologic changes or spontaneous epilepsy (Holmes et al., 1984; Wong et al., 2003). Therefore, the PTZ model offers an opportunity to isolate the direct effects of seizures on the mTOR pathway, in the absence of chronic epileptogenesis.…”

Do vaccines cause epilepsy? Review of cases in the National Vaccine Injury Compensation Program

“…With the possible exception of FSE, which will be discussed below, there is no scientific evidence to support the contention that single or recurrent febrile seizures cause cell loss, apoptosis, aberrant mossy fiber sprouting, or epilepsy. 65,66 Likewise, animal studies do not show that single 67,68 or repeated afebrile seizures [69][70][71] result in cell loss or epilepsy.…”

mTOR-Related Cell-Clearing Systems in Epileptic Seizures, an Update

“…For instance, pentylenetetrazole (PTZ) is a GABA a receptor antagonist used to induce seizures in experimental settings through decreasing inhibitory GABA activity. PTZ's effect is most prominent in the cortex and hippocampus, and its acute administration is a valuable model of generalized tonic-clonic and myoclonic seizures [107,108], while repetitive administrations of PTZ (kindling) are needed to induce SE and pathological alterations [109,110]. Chemical kindling seizures triggered by PTZ are assumed to mimic the pathogenesis of human epilepsy and are considered a model of drug-resistant epilepsy [109,110].…”

Pentylenetetrazole‐induced seizures cause acute, but not chronic, mTOR pathway activation in rat

“…Although in the kainate and pilocarpine models, a second, chronic phase of mTOR activation occurs over days to weeks following the initial seizures (Zeng et al., 2009; Huang et al., 2010), there is no such secondary, late mTOR activation following PTZ seizures. Because PTZ seizures do not typically lead to neuropathologic injury or spontaneous epilepsy (Holmes et al., 1984; Wong et al., 2003), this suggests that the acute phase of seizure‐induced mTOR activation is not sufficient to trigger epileptogenesis. By comparison, after resolution of the acute seizures in the kainate and pilocarpine models, subsequent inhibition of the later phase of mTOR activation has been implicated in suppressing pathologic changes (Buckmaster et al., 2009) and spontaneous seizures (Zeng et al., 2009; Huang et al., 2010) that develop in these other models.…”

“…Then, a second, more chronic phase of mTOR activation evolves over days to weeks and correlates with the process of epileptogenesis and eventual development of spontaneous seizures. In contrast to the kainate model, pentylenetetrazole (PTZ) is an antagonist of γ‐aminobutyric acid (GABA) receptors that induces acute seizures in rodents, but without repetitive applications of PTZ (kindling), this exposure does not appear to lead to significant pathologic changes or spontaneous epilepsy (Holmes et al., 1984; Wong et al., 2003). Therefore, the PTZ model offers an opportunity to isolate the direct effects of seizures on the mTOR pathway, in the absence of chronic epileptogenesis.…”

Do vaccines cause epilepsy? Review of cases in the National Vaccine Injury Compensation Program

“…With the possible exception of FSE, which will be discussed below, there is no scientific evidence to support the contention that single or recurrent febrile seizures cause cell loss, apoptosis, aberrant mossy fiber sprouting, or epilepsy. 65,66 Likewise, animal studies do not show that single 67,68 or repeated afebrile seizures [69][70][71] result in cell loss or epilepsy.…”

mTOR-Related Cell-Clearing Systems in Epileptic Seizures, an Update

“…For instance, pentylenetetrazole (PTZ) is a GABA a receptor antagonist used to induce seizures in experimental settings through decreasing inhibitory GABA activity. PTZ's effect is most prominent in the cortex and hippocampus, and its acute administration is a valuable model of generalized tonic-clonic and myoclonic seizures [107,108], while repetitive administrations of PTZ (kindling) are needed to induce SE and pathological alterations [109,110]. Chemical kindling seizures triggered by PTZ are assumed to mimic the pathogenesis of human epilepsy and are considered a model of drug-resistant epilepsy [109,110].…”