Toward evidence‐based severity assessment in rat models with repeated seizures: II. Chemical post–status epilepticus model

Abstract

Objective Considering the complexity of neuronal circuits and their epilepsy‐associated alterations, epilepsy models cannot be completely replaced by in vitro experimental approaches. Decisions about ethical approval of in vivo studies require a thorough weighing of the animal's burden and the benefit regarding the expected gain in knowledge. Methods Based on combined behavioral, biochemical, and physiological analyses, we assessed the impact on animal well‐being and condition in different phases of the pilocarpine post–status epilepticus (SE) model in rats. Results As a consequence of SE, increased levels of impairment were evident in the early postinsult phase and late chronic phase, whereas only mild impairment was observed in the interim phase. Parameters that stood out as sensitive indicators of animal distress include burrowing, which proved to be affected throughout all experimental phases, saccharin preference, fecal corticosterone metabolites, heart rate, and heart rate variability. Significance The cumulative burden with temporary but not long‐lasting phases of more pronounced impairment suggests a classification of severe as a basis for laboratory‐specific prospective and retrospective evaluation. Among the parameters analyzed, burrowing behavior and saccharin preference stand out as candidate parameters that seem to be well suited to obtain information about animal distress in epileptogenesis models.

Design of composite measure schemes for comparative severity assessment in animal-based neuroscience research: A case study focussed on rat epilepsy models

“…The data used in this study was originally published in five individual studies, investigating three different rat epilepsy models [12][13][14][15][16]. A total of seven subprojects were carried out.…”

“…Electrical post-status epilepticus model [12,13]. Status epilepticus was induced according to Walker et al [18].…”

“…Therefore, a national research consortium FOR2591 (https://severity-assessment.de/) has been initiated to develop new strategies for severity assessment [2]. In our laboratory, we have recently completed a comprehensive analysis of behavioral and biochemical parameters in five studies with analysis in three different rat epilepsy models [12][13][14][15][16], which are among the most common models applied in epilepsy research [28]. Multivariate analysis of data sets from these studies resulted in the identification of the most informative parameters, which were integrated into a candidate composite measure scheme (CMS).…”

“…Saccharin preference is a well-established paradigm frequently applied to assess anhedonia in neuropsychiatric research [23,24]. This parameter has recently been successfully integrated into severity assessment concepts in our previous studies that contributed to the data set used in the present study [12][13][14][15][16]. Activity and social interaction represent parameters that are often integrated into common clinical scores as indicators of animal wellbeing.…”

Dynamic-related protein 1 inhibitor eases epileptic seizures and can regulate equilibrative nucleoside transporter 1 expression

“…Rats in the experimental group were injected with pilocarpine (30 mg/kg, i.p. ; Sigma) [20,21], and rats in the control group received the same treatment (both lithium chloride and atropine sulfate), except that saline was used instead of pilocarpine. Only those rats exhibiting sustained severe SE with convulsive seizures (Class IV-V) were included for further studies [22].…”