Self-sustaining limbic status epilepticus induced by ‘continuous’ hippocampal stimulation: electrographic and behavioral characteristics

Lothman, Eric W.; Bertram, Edward H.; Bekenstein, Jonathan W.; Perlin, Jonathan B.

doi:10.1016/0920-1211(89)90038-7

Cited by 279 publications

(180 citation statements)

References 17 publications

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“…Ten days after electrode implantation, 59 mice were subjected to electrically induced SE, as originally described by Lothman et al (1989). Mice received 1 h of suprathreshold stimulation consisting of 10 s trains of 1 ms biphasic square wave pulses at a frequency of 50 Hz.…”

Section: Tnf-r1/r2mentioning

confidence: 99%

“…In rats, the seizure-generated mature neurons can survive for at least 6 months (Bonde et al, 2006). We induced SE by applying 1 h of electrical stimulation to the hippocampus (Lothman et al, 1989;Mohapel et al, 2004). During the subsequent 2 h of self-sustained SE, all groups of mice exhibited either partial (grade 0 -2) or generalized (grade 3-5) convulsive behavior (Fig.…”

Section: Deletion Of Tnf-r1 and Tnf-r2 Differentially Affects Hippocamentioning

confidence: 99%

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Tumor Necrosis Factor Receptor 1 Is a Negative Regulator of Progenitor Proliferation in Adult Hippocampal Neurogenesis

Iosif

Ekdahl²,

Ahlenius³

et al. 2006

J. Neurosci.

422

297

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Tumor necrosis factor-␣ (TNF-␣) is a proinflammatory cytokine, acting through the TNF-R1 and TNF-R2 receptors. The two receptors have been proposed to mediate distinct TNF-␣ effects in the CNS, TNF-R1 contributing to neuronal damage and TNF-R2 being neuroprotective. Whether TNF-␣ and its receptors play any role for neurogenesis in the adult brain is unclear. Here we used mouse models with loss of TNF-R1 and TNF-R2 function to establish whether signaling through these receptors could influence hippocampal neurogenesis in vivo under basal conditions, as well as after status epilepticus (SE), which is associated with inflammation and elevated TNF-␣ levels. Notably, in the intact brain, the number of new, mature hippocampal neurons was elevated in TNF-R1Ϫ/Ϫ and TNF-R1/R2 Ϫ/Ϫ mice, whereas no significant changes were detected in TNF-R2 Ϫ/Ϫ mice. Also after SE, the TNF-R1 Ϫ/Ϫ and TNF-R1/R2 Ϫ/Ϫ mice produced more new neurons. In contrast, the TNF-R2 Ϫ/Ϫ mice showed reduced SE-induced neurogenesis. Cell proliferation in the dentate subgranular zone was elevated in TNF-R1 Ϫ/Ϫ and TNF-R1/R2 Ϫ/Ϫ mice both under basal conditions and after SE. The TNF-R2 Ϫ/Ϫ mice either showed no change or minor decrease of cell proliferation. TNF-R1 and TNF-R2 receptors were expressed by hippocampal progenitors, as assessed with reverse transcription-PCR on sorted or cultured cells and immunocytochemistry on cultures. Our data reveal differential actions of TNF-R1 and TNF-R2 signaling in adult hippocampal neurogenesis and identify for the first time TNF-R1 as a negative regulator of neural progenitor proliferation in both the intact and pathological brain.

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Section: Tnf-r1/r2mentioning

confidence: 99%

Section: Deletion Of Tnf-r1 and Tnf-r2 Differentially Affects Hippocamentioning

confidence: 99%

Tumor Necrosis Factor Receptor 1 Is a Negative Regulator of Progenitor Proliferation in Adult Hippocampal Neurogenesis

Iosif

Ekdahl²,

Ahlenius³

et al. 2006

J. Neurosci.

422

297

View full text Add to dashboard Cite

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“…DeGiorgio and colleagues (503 1) found elevated neuron-specific enolase in cerebrospinal fluid and serum during complex partial and myoclonic NCSE. A rat model of NCSE results from a brief 90-minute period of continuous electrical hippocampal stimulation that induces 12 to 24 hours of NCSE centered in the limbic system (65). Approximately 6 weeks later, the animals develop spontaneous recurrent seizures and pathologic changes identical to human mesial temporal sclerosis (66).…”

Section: Nonconvulsive Status Epilepticusmentioning

confidence: 99%

Status Epilepticus: Risk Factors and Complications

2000

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Summary: Status epilepticus is common and associated with significant mortality and complications. It affects approximately 50 patients per 100,000 population annually and recurs in >13%. History of epilepsy is the strongest single risk factor for generalized convulsive status epilepticus. More than 15% of patients with epilepsy have at least one episode of status epilepticus and low antiepileptic drug levels are a potentially modifiable risk factor. Other risks include young age, genetic predisposition, and acquired brain insults. Fever is a very common risk in children, as is stroke in adults. Mortality rates are 15% to 20% in adults and 3% to 15% in children. Acute complications result from hyperthermia, pulmonary edema, cardiac arrhythmias, and cardiovascular collapse. Long‐term complications include epilepsy (20% to 40%), encephalopathy (6% to 15%), and focal neurologic deficits (9% to 11%). Neuronal injury leading to temporal lobe epilepsy is probably mediated by excess excitation via activation of the N‐methyl‐D‐aspartate (NMDA) subtype of glutamate receptors and consequent elevated intracellular calcium that causes acute necrosis and delayed apoptotic cell death. Some forms of nonconvulsive status epilepticus may also lead to neuronal injury by this mechanism, but others may not. Based on clinical and experimental observations, complex partial status epilepticus is more likely to result in neuronal injury similar to generalized convulsive status epilepticus. Absence status epilepticus is much less likely to result in neuronal injury, and complications because it may be mediated primarily through excess inhibition. Future research strategies to prevent complications of status epilepticus include the study of new drugs (including NMDA antagonists, new drug delivery systems, and drug combinations) to stop seizure activity and prevent acute and delayed neuronal injury that leads to the development of epilepsy.

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“…The technique has been fully described previously (23). The animals were not treated during the course of SE.…”

Section: Surgerymentioning

confidence: 99%

Functional Anatomy of Spontaneous Seizures in a Rat Model of Limbic Epilepsy

Bertram

1997

Epilepsia

142

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Summary: Purpose: The substrate of seizure initiation in partial epilepsy is not well understood. Although many studies imply a focus that is will localized to a single structure, some information suggests that seizures arise regionally with simultaneous or near-simultaneous onset at several separate sites. To determine the physiological pattern of seizure onset, recordings were made of spontaneous seizures from multiple limbic structures in a rat model of limbic epilepsy.Methods: Seventeen rats with chronic spontaneous limbic seizures that occurred after an episode of electrical hippocampal stimulation-induced status epilepticus (SE) underwent chronic recording of seizures with a minimum of four electrodes placed bilaterally in the midventral hippocampus and either the amygdala or piriform cortex. As many as 15 of the first recorded spontaneous seizures (mean of 12 seizures, range 2-15) was evaluated for each animal with regard to pattern of seizure onset (focal hippocampal, focal nonhippocampal, or diffuse). The results were evaluated for number of seizure patterns displayed by each animal and the potential change in the pattern of onset with successive seizures (from the first to the fifteenth).Results: In all, 210 seizures were evaluated, beginning 1 week after SE and with monitoring lasting G 18 weeks (mean recording duration 6 weeks) to record a maximum of 15 seizures for each animal. Overall, 54% of the seizures were of diffuse onset, 25% were of nonhippocampal onset, and 21% were of hippocampal onset. Eight of the 17 (47%) animals had seizures with all three patterns of onset. Evaluation of the evolution of the pattern of onset from the first to the fifteenth seizure recorded for the animals showed a clear tendency for the later seizures to have diffuse onsets (regression analysis r = 0.737, p < 0.002). Qualitative histologic analysis demonstrated neuronal loss in the recorded regions.Conclusions: These findings indicate that the epileptogenic zone is broad in this model of limbic "focal" epilepsy and suggest that the substrate for seizure generation is distributed over several structures. Key Words: Epilepsy-Functional anatomy-Limbic seizures-Animal models.Although the functional anatomy for primarily generalized epilepsy is relatively well established as a perturbation in the thalamocortical circuits (1,2), the substrate for the generation of mesial temporal lobe seizures, one of the common forms of partial epilepsy, is not known, but several mechanisms have been proposed (3). The debate in part involves the degree of focality in the physiologic processes that generate the spontaneous seizures. The more focal theories suggest that a single key pathological entity [e.g., mossy fiber sprouting and dentate gyrus synaptic reorganization (4-6) or dormant intemeurons (7)] or a specific region exists (e.g., CA3, fascia dentata) that is the primary contributor to the generation of seizures. the other end of the hypothesis (least focal) holds that the seizures result from a widespread derangement in the physiol...

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Self-sustaining limbic status epilepticus induced by ‘continuous’ hippocampal stimulation: electrographic and behavioral characteristics

Cited by 279 publications

References 17 publications

Tumor Necrosis Factor Receptor 1 Is a Negative Regulator of Progenitor Proliferation in Adult Hippocampal Neurogenesis

Tumor Necrosis Factor Receptor 1 Is a Negative Regulator of Progenitor Proliferation in Adult Hippocampal Neurogenesis

Status Epilepticus: Risk Factors and Complications

Functional Anatomy of Spontaneous Seizures in a Rat Model of Limbic Epilepsy

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