Kainic Acid-Induced Post-Status Epilepticus Models of Temporal Lobe Epilepsy with Diverging Seizure Phenotype and Neuropathology

Bertoglio, Daniele; Amhaoul, Halima; Eetveldt, Annemie Van; Houbrechts, Ruben; Vijver, Sebastiaan Van De; Ali, Idrish; Dedeurwaerdere, Stefanie

doi:10.3389/fneur.2017.00588

Cited by 63 publications

(59 citation statements)

References 57 publications

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“…4,6,28,29 Others report F I G U R E 6 DC shifts recorded in 125-µm conditioned-silver brainstem electrode following lethal apneas. 31 Other confounds include strain differences in susceptibility, 32 sex, type of anesthetic, type of convulsant, and route of administration. As in Figure 5, nasal signal shows cessation of respiration while brainstem unit activity (recorded with 25-µm Pt/Ir electrode) and derived EMG activity continue for over 10 s. Note brainstem discharge on both brainstem recordings following final attempt to breathe.…”

Section: Cardiovascular Changesmentioning

confidence: 99%

“…4,30 This discrepancy could depend on relative levels of sympathetic and parasympathetic activity and/or on starting heart rate. 31 Other confounds include strain differences in susceptibility, 32 sex, type of anesthetic, type of convulsant, and route of administration. Unlike focal injections into a restricted area of the brain, systemic administration of convulsants may include widespread non-seizure-related responses to actions at multiple cardiorespiratory centers.…”

Section: Cardiovascular Changesmentioning

confidence: 99%

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Brainstem activity, apnea, and death during seizures induced by intrahippocampal kainic acid in anaesthetized rats

et al. 2019

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Objective: To investigate how prolonged seizure activity affects cardiorespiratory function and activity of pre-Bötzinger complex, leading to sudden death. Methods: Urethane-anesthetized female Long-Evans rats were implanted with nasal thermocouple; venous and arterial cannulae; and electrodes for electrocardiography (ECG) and hippocampal, cortical, and brainstem recording. Kainic acid injection into the ventral hippocampus induced status epilepticus. Results: Seizures caused hypertension, tachycardia, and tachypnea punctuated by recurrent transient apneas. Salivation increased considerably: in 11 of 12 rats, liquid with alkaline pH consistent with saliva was expelled from the mouth. Most transient apneas were obstructive: nasal airflow ceased, while, in 83%, efforts to breathe persisted as continued rhythmic activity of respiratory pre-Bötzinger neurons, inspiratory electromyography (EMG), and excursions of the chest wall and abdomen. Blood pressure oscillated in time with respiratory efforts. This pattern also occurred in a minority of cases (16%) of incomplete apnea, but not in rare cases (1%) of transient central apneas. During transient obstructive apneas, the frequency of all inspiratory efforts decreased abruptly by ~30%, suggesting a resetting of the central respiratory rhythm generator. Twenty-two of thirty-one rats died, due either to obstructive apnea (12) or central apnea following progressive slowing of respiration (10). Most rats dying of central apnea had experienced several transient obstructive apneas.Negative DC field potential shifts of the brainstem followed the final breath, consistent with previous reports on spreading depolarization in mouse models. Timing suggests that the DC shift is a consequence rather than cause of respiratory collapse.Cardiac activity continued for tens of seconds. Significance: Seizure activity in forebrain induces pronounced autonomic activation and disrupts activity in medullary respiratory centers, resulting in death from either obstructive or central apnea. These results directly inform mechanisms of death in status epilepticus, and indirectly provide clues to mechanisms of sudden unexpected death in epilepsy (SUDEP). K E Y W O R D SHeart rate, obstructive apnea, status epilepticus, SUDEP | 2347 JEFFERYS Et al.

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Section: Cardiovascular Changesmentioning

confidence: 99%

Section: Cardiovascular Changesmentioning

confidence: 99%

Brainstem activity, apnea, and death during seizures induced by intrahippocampal kainic acid in anaesthetized rats

et al. 2019

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“…3,10,[34][35][36][37] For Ox-42 staining, images of ROIs were taken at 4× magnification with an AxioCam Erc5s (ZEISS, Germany) and converted into 8-bit images in ImageJ. ROI included the entire hippocampal cornu ammonis (CA)1, CA3, CA4, hilar sub-regions, and piriform cortex (PC).…”

Section: Immunohistochemistrymentioning

confidence: 99%

“…The protocols for NeuN, OX-42, CD-68, and GFAP staining were published previously. 9,10,[34][35][36][37] The antibodies used in the immunohistochemical experiments are listed in Table 1.…”

Section: Immunohistochemistrymentioning

confidence: 99%

“…The specific details for the different evaluation methods are outlined below. 3,10,[34][35][36][37] For Ox-42 staining, images of ROIs were taken at 4× magnification with an AxioCam Erc5s (ZEISS, Germany) and converted into 8-bit images in ImageJ. Using ImageJ, an intensity threshold was set visually to detect all stained cells above background.…”

Section: Immunohistochemistrymentioning

confidence: 99%

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Spatiotemporal expression and inhibition of prolyl oligopeptidase contradict its involvement in key pathologic mechanisms of kainic acid–induced temporal lobe epilepsy in rats

et al. 2018

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Summary Objective Prolyl oligopeptidase (PREP) has been implicated in neuroinflammatory processes and neuroplasticity and has been suggested as a target for the treatment of neurodegenerative disease. The aim of this investigation was to explore the involvement of PREP in the neuropathologic mechanisms relevant to temporal lobe epilepsy (TLE) using a PREP inhibitor in a well‐established rat model. Methods PREP activity and expression was studied in Sprague‐Dawley rats 2 and 12 weeks following kainic acid–induced status epilepticus (KASE). Continuous video‐electroencephalography monitoring was performed for 2 weeks in the 12‐week cohort to identify a relationship of PREP expression/activity with epileptic seizures. In addition, the animals included in the 2‐week time point were treated with a specific inhibitor of PREP, KYP‐2047, or saline continuously, starting immediately after SE. PREP activity and its expression were analyzed in rat brain by using enzyme kinetics and western blot. In addition, markers for microglial activation, astrogliosis, cell loss, and cell proliferation were evaluated. Results Enzymatic activity of PREP was unchanged following induction of SE after 2 and 12 weeks in rats. PREP activity in epileptic rats did not relate to the number of seizures/day at the 12‐week time point. Moreover, continuous inhibition of PREP for 2 weeks after KASE did not alter the SE‐mediated neuroinflammatory response, cell loss, or cell proliferation in the hippocampal subgranule zone measured at the 2‐week time point. Significance PREP inhibition does not affect key pathologic mechanisms, including activation of glial cells, cell loss, and neural progenitor cell proliferation, in this KASE model of TLE. The results do not support a direct role of PREP in seizure burden during the chronic epilepsy period in this model.

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Neurodegenerative pathways as targets for acquired epilepsy therapy development

2020

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There is a growing body of clinical and experimental evidence that neurodegenerative diseases and epileptogenesis after an acquired brain insult may share common etiological mechanisms. Acquired epilepsy commonly develops as a comorbid condition in patients with neurodegenerative diseases such as Alzheimer's disease, although it is likely much under diagnosed in practice. Progressive neurodegeneration has also been described after traumatic brain injury, stroke, and other forms of brain insults. Moreover, recent evidence has shown that acquired epilepsy is often a progressive disorder that is associated with the development of drug resistance, cognitive decline, and worsening of other neuropsychiatric comorbidities. Therefore, new pharmacological therapies that target neurobiological pathways that underpin neurodegenerative diseases have potential to have both an anti-epileptogenic and diseasemodifying effect on the seizures in patients with acquired epilepsy, and also mitigate the progressive neurocognitive and neuropsychiatric comorbidities. Here, we review the neurodegenerative pathways that are plausible targets for the development of novel therapies that could prevent the development or modify the progression of acquired epilepsy, and the supporting published experimental and clinical evidence. K E Y W O R D SAMPA, amyloid-β, glutamate, mTOR, neuroinflammation, tau

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Kainic Acid-Induced Post-Status Epilepticus Models of Temporal Lobe Epilepsy with Diverging Seizure Phenotype and Neuropathology

Cited by 63 publications

References 57 publications

Brainstem activity, apnea, and death during seizures induced by intrahippocampal kainic acid in anaesthetized rats

Brainstem activity, apnea, and death during seizures induced by intrahippocampal kainic acid in anaesthetized rats

Spatiotemporal expression and inhibition of prolyl oligopeptidase contradict its involvement in key pathologic mechanisms of kainic acid–induced temporal lobe epilepsy in rats

Neurodegenerative pathways as targets for acquired epilepsy therapy development

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