Animal models of tumour-associated epilepsy

Kirschstein, Timo; Köhling, Rüdiger

doi:10.1016/j.jneumeth.2015.06.008

Cited by 13 publications

(6 citation statements)

References 114 publications

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“…To conduct the in vivo experiments with respect to orthotopic glioma progression and onset of tumor-related seizures, a robust animal model was needed. F98 glioma in Fischer rats is a wellestablished glioma model (Belloli et al, 2013;Schültke et al, 2018;Wang et al, 2018), but to the best of our knowledge, no data about its tumor-associated epileptiform phenotype have been published so far (Kirschstein and Köhling, 2016). The results of our studies suggest that F98 glioma led to interictal epileptiform events (e.g., spikes and spike-waves), indicating a high susceptibility to develop seizures, which was also demonstrated by video-EEG analysis.…”

Section: Discussionsupporting

confidence: 67%

“…First, we established a rat glioma model that shows both orthotopic glioma progression and tumor-associated symptomatic epilepsy. While in vivo implantation of F98 cells is a well-known glioma model (Kirschstein and Köhling, 2016), the epileptic phenotype has not yet been addressed. In prolonged video-EEG recordings, we could show that both epileptiform EEG potentials and motor seizures occurred during the pre-final clinical stage [from day 9 to 2 (relative to sacrifice); Figure 1A and Supplementary Figure 3].…”

Section: Orthotopic F98 Glioma Is a Valuable Model For The Human Diseasementioning

confidence: 99%

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Perampanel Add-on to Standard Radiochemotherapy in vivo Promotes Neuroprotection in a Rodent F98 Glioma Model

et al. 2020

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An abnormal glutamate signaling of glioblastoma may contribute to both tumor progression and the generation of glioma-associated epileptic seizures. We hypothesized that the AMPA receptor antagonist perampanel (PER) could attenuate tumor growth and epileptic events. F98 glioma cells, grown orthotopically in Fischer rats, were employed as a model of glioma to investigate the therapeutic efficiency of PER (15 mg/kg) as adjuvant to standard radiochemotherapy (RCT). The epileptiform phenotype was investigated by video-EEG analysis and field potential recordings. Effects on glioma progression were estimated by tumor size quantification, survival analysis and immunohistological staining. Our data revealed that orthotopically-growing F98 glioma promote an epileptiform phenotype in rats. RCT reduced the tumor size and prolonged the survival of the animals. The adjuvant administration of PER had no effect on tumor progression. The tumor-associated epileptic events were abolished by PER application or RCT respectively, to initial baseline levels. Remarkably, PER preserved the glutamatergic network activity on healthy peritumoral tissue in RCT-treated animals. F98 tumors are not only a robust model to investigate glioma progression, but also a viable model to simulate a glioma-associated epileptiform phenotype. Furthermore, our data indicate that PER acts as a potent anticonvulsant and may protect the tumor-surrounding tissue as adjuvant to RCT, but failed to attenuate tumor growth or promote animal survival.

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Section: Discussionsupporting

confidence: 67%

Section: Orthotopic F98 Glioma Is a Valuable Model For The Human Diseasementioning

confidence: 99%

Perampanel Add-on to Standard Radiochemotherapy in vivo Promotes Neuroprotection in a Rodent F98 Glioma Model

et al. 2020

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“…In order to reliably verify tumor-associated seizures, EEG recordings are required, supported by video recordings. To the best of our knowledge, only a small number of in vivo rodent models with glioma-associated epilepsy are published so far [ 184 ].…”

Section: Preclinical Models To Study Glutamate Interaction and Tumor-associated Epilepsymentioning

confidence: 99%

Glutamatergic Mechanisms in Glioblastoma and Tumor-Associated Epilepsy

Lange

Hörnschemeyer

Kirschstein

2021

Cells

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The progression of glioblastomas is associated with a variety of neurological impairments, such as tumor-related epileptic seizures. Seizures are not only a common comorbidity of glioblastoma but often an initial clinical symptom of this cancer entity. Both, glioblastoma and tumor-associated epilepsy are closely linked to one another through several pathophysiological mechanisms, with the neurotransmitter glutamate playing a key role. Glutamate interacts with its ionotropic and metabotropic receptors to promote both tumor progression and excitotoxicity. In this review, based on its physiological functions, our current understanding of glutamate receptors and glutamatergic signaling will be discussed in detail. Furthermore, preclinical models to study glutamatergic interactions between glioma cells and the tumor-surrounding microenvironment will be presented. Finally, current studies addressing glutamate receptors in glioma and tumor-related epilepsy will be highlighted and future approaches to interfere with the glutamatergic network are discussed.

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“…For instance, Cx43 interacts with ZO-1 protein, which could prevent the cytoplasmic localization and lead to glioma cell invasion (12,76). Cx43 interacts with other cytoskeleton proteins and tight junctions or adherens junctions associated with proteins, including tubulin, cadherins, catenin and actin, to modulate polarity, motility and directional migration of cells (12,24,77,78). In addition, Cx43 interacts with c-Src and inhibits Src activity, sequentially modulating cell polarity, motility and invasion through several signaling pathways (Fig.…”

Section: Controversy Of the Effect Of Cx43 On Glioma Cell Invasion Anmentioning

confidence: 99%

Complex role of connexin 43 in astrocytic tumors and possible promotion of glioma-associated epileptic discharge

Dong

Zhou

Wang

et al. 2017

Molecular Medicine Reports

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Connexin (Cx)43 is a multifunction protein which forms gap junction channels and hemi‑channels. It also contains abundant binding domains which possess the ability to interact with certain Cx43‑associated proteins and therefore serve a fundamental role in various physiological and pathological functions. However, the understanding of the association between cancer and Cx43 along with Cx43‑gap junctions (GJ) remains unclear. All available data illustrate that Cx43 and its associated GJ serve important functions in cancers. The expression levels of Cx43 demonstrate a downward trend and an increase in the levels of malignancy, particularly in astrocytomas. The GJ intercellular communication activity in glioma cells can be adjusted via Cx43 phosphorylation and through the combination of Cx43 and its associated protein. Available evidence reveals Cx43 as a tumor‑inhibiting factor that suppresses glioma growth and proliferation. However, its mechanism is also regarded as complicated and ambiguous. Furthermore, it is apparent that Cx43‑GJ and the carboxyl tail may contribute to glioma growth and proliferation too. However, this valuable role could be weakened by its effects on migration and invasiveness. The detailed mechanism remains unclear and full of controversies. Cx43 can enhance the motor ability and invasiveness of astrocytic glioma cells. It is also able to influence glioma cells to detach from the tumor core to the peritumoral neocortex. This peritumoral region has recently been regarded as the basic focus of glioma‑associated seizure. Thus, Cx43 may take part in the onset and development of glioma‑associated epileptic discharge. In addition, change and increase of Cx43 expression in GJs has been observed in seizure perilesional tissue, which is associated with brain tumors. Cx43 or GJ/hemi‑channels exert enduring effects in the promotion of glioma‑associated epileptic release through direct mass effects and change of the tumor microenvironment. However, there are still a number of issues concerning this aspect that require further exploration. Cx43, as a potential treatment target against this incurable disease and its common symptom of epilepsy, requires further investigation.

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Animal models of tumour-associated epilepsy

Cited by 13 publications

References 114 publications

Perampanel Add-on to Standard Radiochemotherapy in vivo Promotes Neuroprotection in a Rodent F98 Glioma Model

Perampanel Add-on to Standard Radiochemotherapy in vivo Promotes Neuroprotection in a Rodent F98 Glioma Model

Glutamatergic Mechanisms in Glioblastoma and Tumor-Associated Epilepsy

Complex role of connexin 43 in astrocytic tumors and possible promotion of glioma-associated epileptic discharge

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