Imaging biomarkers of behavioral impairments: A pilot micro–positron emission tomographic study in a rat electrical post–status epilepticus model

Abstract

Objective:In patients with epilepsy, psychiatric comorbidities can significantly affect the disease course and quality of life. Detecting and recognizing these comorbidities is central in determining an optimal treatment plan. One promising tool in detecting biomarkers for psychiatric comorbidities in epilepsy is positron emission tomography (PET). Methods: Behavioral and biochemical variables were cross-correlated with the results from two μPET scans using the tracers [ 18 F]fluoro-2-deoxy-D-glucose ([ 18 F]FDG) and 2′-methoxyphenyl-(N-2′-pyridinyl)-p-18 F-fluoro-benzamidoethylpiperazine ([ 18 F]MPPF) to explore potential biomarkers for neurobehavioral comorbidities in an electrically induced post-status epilepticus rat model of epilepsy.Results: In rats with epilepsy, μPET analysis revealed a local reduction in hippocampal [ 18 F]FDG uptake, and a local increase in [ 18 F]MPPF binding. These changes exhibited a correlation with burrowing as a "luxury" behavior, social interaction, and anxiety-associated behavioral patterns. Interestingly, hippocampal [ 18 F]FDG uptake did not correlate with spontaneous recurrent seizure activity. Significance: In the electrically induced post-status epilepticus rat model, we demonstrated hippocampal hypometabolism and its correlation with a range of neurobehavioral alterations. These findings require further confirmation in other preclinical models and patients with epilepsy and psychiatric disorders to address the value of [ 18 F]FDG uptake as an imaging biomarker candidate for psychiatric comorbidities in patients as well as for severity assessment in rodent epilepsy models.

Toward evidence‐based severity assessment in rat models with repeated seizures: III. Electrical post‐status epilepticus model

“…In addition, behavioral test batteries in the electrical post-SE and other epilepsy models can be used to assess correlations between potential biomarker candidates and behavioral parameters under standardized conditions. 38,39 Finally, we were eager to obtain further information about whether replacement of tethered seizure monitoring by telemetric seizure monitoring reduces the burden for the animals as suggested by Lidster et al 2 Our findings from the pilocarpine model revealed that minor differences can be observed between animals with tethered and telemetric recordings with evidence for a higher level of distress in the group with tethered monitoring (Koska et al, manuscript in revision).…”

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.…”

“…Chemical post-status epilepticus model [15,16]. Following a three week recovery period animals were injected with lithium chloride (i.p.…”

“…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.…”