The pilocarpine model of temporal lobe epilepsy: Marked intrastrain differences in female Sprague–Dawley rats and the effect of estrous cycle

Brandt, Claudia; Bankstahl, Marion; Töllner, Kathrin; Klee, Rebecca; Löscher, Wolfgang

doi:10.1016/j.yebeh.2016.05.020

Cited by 25 publications

(33 citation statements)

References 48 publications

(113 reference statements)

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“…As in the study with Wistar rats, we obtained details of the breeding conditions from the vendors, housing, and handling procedures (Table 2). Similar experiments were performed with the lithium-pilocarpine model of TLE [37]. As shown in Table 2, only Janvier performed daily handling habituation during rearing of the SD rats, resulting in socialization to humans.…”

Section: Inter- and Intra-strain Differences Affect Performance Inmentioning

confidence: 97%

“…Following intrahippocampal administration of 10 mM pilocarpine, CRL1 rats were significantly more prone to seizures than the CRL2 and HAR HAN rats, while the CRL HAN rats showed similar seizure susceptibility as the CRL1 rats [18]. The latter study prompted us to compare the consequences of systemic administration of pilocarpine (following pretreatment with lithium) in SD rats from different breeders (Harlan, Charles River [CRL], Taconic) as well as different breeding locations of the same breeder (Harlan-Winkelmann [HW] in Germany vs. Harlan Laboratories [HL] in the Netherlands) [37]. Pilocarpine was administered by a ramp- up dosing protocol that allows determining inter-individual differences in susceptibility to the convulsant.…”

Section: Intrastrain Differences In Mice and Ratsmentioning

confidence: 99%

“…In 17 rats used for pilocarpine experiments, SE could not be induced in any rat [37]. This sharply distinguished this Wistar substrain from Wistar rats from Harlan-Winkelmann (Wistar Unilever) that we had previously used for several pilocarpine experiments, resulting in an overall incidence of SE of 68% of a group of 170 rats by the ramp-up protocol [37]. …”

Section: Intrastrain Differences In Mice and Ratsmentioning

confidence: 99%

“…Results from SD rats have not shown major differences in the development of behavioral and electrographic alterations [130,131], while ameliorating the mortality rates [29]. In a recent study in which SE was induced in female Wistar and SD rats by lithium-pilocarpine [37], Wistar and SD rats obtained from the same breeder (Harlan-Winkelmann) in Germany did not differ in SE induction (68 vs. 74%) or percent of rats developing SRS (90 vs. 100%)(Table 1), whereas SD rats from other breeders were less sensitive (see section 2.2). Pilocarpine effects were more pronounced in Long-Evans rats, in which a higher mortality rate, larger damage to the hippocampus and a behavioral outcome worse than in Wistar rats was found [132].…”

Section: Interstrain Differences In the Expression Of Seizures Andmentioning

confidence: 99%

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The relevance of inter- and intrastrain differences in mice and rats and their implications for models of seizures and epilepsy

Löscher¹,

Ferland

Ferraro

2017

Epilepsy & Behavior

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It is becoming increasingly clear that the genetic background of mice and rats, even in inbred strains, can have a profound influence on measures of seizure susceptibility and epilepsy. These differences can be capitalized upon through genetic mapping studies to reveal genes important for seizures and epilepsy. However, strain background and particularly mixed genetic backgrounds of transgenic animals need careful consideration in both the selection of strains and in the interpretation of results and conclusions. For instance, mice with targeted deletions of genes involved in epilepsy can have profoundly disparate phenotypes depending on the background strain. In this review, we discuss findings related to how this genetic heterogeneity has and can be utilized in the epilepsy field to reveal novel insights into seizures and epilepsy. Moreover, we discuss how caution is needed in regards to rodent strain or even animal vendor choice, and how this can significantly influence seizure and epilepsy parameters in unexpected ways. This is particularly critical in decisions regarding the strain of choice used in generating mice with targeted deletions of genes. Finally, we discuss the role of environment (at vendor and/or laboratory) and epigenetic factors for inter- and intrastrain differences and how such differences can affect the expression of seizures and the animals’ performance in behavioral tests that often accompany acute and chronic seizure testing.

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Section: Inter- and Intra-strain Differences Affect Performance Inmentioning

confidence: 97%

Section: Intrastrain Differences In Mice and Ratsmentioning

confidence: 99%

Section: Intrastrain Differences In Mice and Ratsmentioning

confidence: 99%

Section: Interstrain Differences In the Expression Of Seizures Andmentioning

confidence: 99%

See 2 more Smart Citations

The relevance of inter- and intrastrain differences in mice and rats and their implications for models of seizures and epilepsy

Löscher¹,

Ferland

Ferraro

2017

Epilepsy & Behavior

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“…Experimentally induced convulsive SE in rodents by neurotoxins such as kainate or pilocarpine or diisopropylfluorophosphate (DFP), an organophosphate, causes irreversible brain damage if not adequately treated immediately (Lemercier et al, 1983; Furtado et al, 2012; Iyer et al, 2015; Brandt et al, 2016; Puttachary et al, 2016a and b). The duration and severity of SE determines the outcome of epileptogenesis.…”

Section: Severity Of Status Epilepticus Determines Epileptogenesismentioning

confidence: 99%

Glial source of nitric oxide in epileptogenesis: A target for disease modification in epilepsy

Sharma

Puttachary

Thippeswamy

2017

J of Neuroscience Research

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Epileptogenesis is the process of developing an epileptic condition and/or its progression once it is established. The molecules that initiate, promote, and propagate remarkable changes in the brain during epileptogenesis are emerging as targets for prevention/treatment of epilepsy. Epileptogenesis is a continuous process that follows immediately after status epilepticus (SE) in animal models of acquired temporal lobe epilepsy (TLE). Both SE and epileptogenesis are potential therapeutic targets for the discovery of anticonvulsants and antiepileptogenic or disease-modifying agents. For translational studies, SE targets are appropriate for screening anticonvulsive drugs prior to their advancement as therapeutic agents, while targets of epileptogenesis are relevant for identification and development of therapeutic agents that can either prevent or modify the disease or its onset. The acute seizure models do not reveal antiepileptogenic properties of anticonvulsive drugs. This review highlights the important components of epileptogenesis and the long-term impact of intervening one of these components, nitric oxide (NO), in rat and mouse kainate models of TLE. NO is a putative pleotropic gaseous neurotransmitter and an important contributor of nitro-oxidative stress that coexists with neuroinflammation and epileptogenesis. The long-term impact of inhibiting the glial source of NO during early epileptogenesis in the rat model of TLE is reviewed. The importance of sex as a biological variable in disease modification strategies in epilepsy is also briefly discussed.

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TSPO PET Identifies Different Anti-inflammatory Minocycline Treatment Response in Two Rodent Models of Epileptogenesis

et al. 2020

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Epileptogenesis-associated brain inflammation might be a promising target to prevent or attenuate epileptogenesis. Positron emission tomography (PET) imaging targeting the translocator protein (TSPO) was applied here to quantify effects of different dosing regimens of the anti-inflammatory drug minocycline during the latent phase in two rodent models of epileptogenesis. After induction of epileptogenesis by status epilepticus (SE), rats were treated with minocycline for 7 days (25 or 50 mg/kg) and mice for 5 or 10 days (50 or 100 mg/kg). All animals were subjected to scans at 1 and 2 weeks post-SE. Radiotracer distribution was analyzed and statistical parametric mapping (SPM) was performed, as well as histological analysis of astroglial activation and neuronal cell loss. Atlas-based analysis of [ 18 F]GE180 PET in rats revealed a dose-dependent regional decrease of TSPO expression at 2 weeks post-SE. Results of SPM analysis depicted a treatment effect already at 1 week post-SE in rats treated with the higher minocycline dose. In mice, TSPO PET imaging did not reveal any treatment effects whereas histology identified only a treatment-related reduction in dispersion of dentate gyrus neurons. TSPO PET served as an auspicious tool for temporal monitoring and quantification of anti-inflammatory effects during epileptogenesis. Importantly, the findings underline the need to applying more than one animal model to avoid missing treatment effects. For future studies, the setup is ready to be applied in combination with seizure monitoring to investigate the relationship between individual early treatment response and disease outcome. Key Words Neuroinflammation. translocator protein. PET. epileptogenesis. minocycline Bettina J. Wolf and Mirjam Brackhan as well as Jens P. Bankstahl and Marion Bankstahl contributed equally to this work.

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The pilocarpine model of temporal lobe epilepsy: Marked intrastrain differences in female Sprague–Dawley rats and the effect of estrous cycle

Cited by 25 publications

References 48 publications

The relevance of inter- and intrastrain differences in mice and rats and their implications for models of seizures and epilepsy

The relevance of inter- and intrastrain differences in mice and rats and their implications for models of seizures and epilepsy

Glial source of nitric oxide in epileptogenesis: A target for disease modification in epilepsy

TSPO PET Identifies Different Anti-inflammatory Minocycline Treatment Response in Two Rodent Models of Epileptogenesis

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