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The provided companion has been developed by the Behavioral Working Group of the Joint Translational Task Force of the International League Against Epilepsy (ILAE) and the American Epilepsy Society (AES) with the purpose of assisting the implementation of Preclinical Common Data Elements (CDE) for studying and for reporting neurobehavioral comorbidities in rodent models of epilepsy. Case Report Forms (CRFs) are provided, which should be completed on a per animal/per test basis, whereas the CDEs are a compiled list of the elements that should be reported. This companion is not designed as a list of recommendations, or guidelines for how the tests should be run-rather, it describes the different types of assessments, and highlights the importance of rigorous data collection and transparency in this regard. The tests are divided into 7 categories for examining behavioral dysfunction on the syndrome level: deficits in learning and memory; depression; anxiety; autism; attention deficit/hyperactivity disorder; psychosis; and aggression. Correspondence and integration of these categories into the National Institute of Mental Health (NIMH) Research Domain Criteria (RDoC) is introduced. Developmental aspects are addressed through the introduction of developmental milestones. Discussion includes complexities, limitations, and biases associated with neurobehavioral testing, especially when performed in animals with epilepsy, as well as the importance of rigorous data collection and of transparent reporting. This represents, to our knowledge, the first such resource dedicated to preclinical CDEs for behavioral testing of rodents.

ObjectiveCommon data elements (CDEs) are currently unavailable for mobile health (mHealth) in epilepsy devices and related applications. As a result, despite expansive growth of new digital services for people with epilepsy, information collected is often not interoperable or directly comparable. We aim to correct this problem through development of industry-wide standards for mHealth epilepsy data.MethodsUsing a group of stakeholders from industry, academia, and patient advocacy organizations, we offer a consensus statement for the elements that may facilitate communication among different systems.ResultsA consensus statement is presented for epilepsy mHealth CDEs.SignificanceAlthough it is not exclusive, we believe that the use of a minimal common information denominator, specifically these CDEs, will promote innovation, accelerate scientific discovery, and enhance clinical usage across applications and devices in the epilepsy mHealth space. As a consequence, people with epilepsy will have greater flexibility and ultimately more powerful tools to improve their lives.

The major objective of preclinical translational epilepsy research is to advance laboratory findings toward clinical application by testing potential treatments in animal models of seizures and epilepsy. Recently there has been a focus on the failure of preclinical discoveries to translate reliably, or even to be reproduced in different laboratories. One potential cause is a lack of standardization in preclinical data collection. The resulting difficulties in comparing data across studies have led to high cost and missed opportunity, which in turn impede clinical trials and advances in medical care. Preclinical epilepsy research has successfully brought numerous antiseizure treatments into the clinical practice, yet the unmet clinical needs have prompted the reconsideration of research strategies to optimize epilepsy therapy development. In the field of clinical epilepsy there have been successful steps to improve such problems, such as generation of common data elements ( CDEs) and case report forms ( CRFs and standards of data collection and reporting) by a team of leaders in the field. Therefore, the Translational Task Force was appointed by the International League Against Epilepsy ( ILAE) and the American Epilepsy Society ( AES), in partnership with the National Institute of Neurological Disorders and Stroke ( NINDS) and the National Institutes of Health ( NIH) to define CDEs for animal epilepsy research studies and prepare guidelines for data collection and experimental procedures. If adopted, the preclinical CDEs could facilitate collaborative epilepsy research, comparisons of data across different laboratories, and promote rigor, transparency, and impact, particularly in therapy development. [ABSTRACT FROM AUTHOR]

The mossy fiber (MF) pathway is critical to hippocampal function and influenced by gonadal hormones. Physiological data are limited, so we asked whether basal transmission and long-term potentiation (LTP) differed in slices of adult male and female rats. The results showed small sex differences in basal transmission but striking sex differences in opioid receptor sensitivity and LTP. When slices were made from females on proestrous morning, when serum levels of 17β-estradiol peak, the nonspecific opioid receptor antagonist naloxone (1 μm) enhanced MF transmission but there was no effect in males, suggesting preferential opioid receptor-dependent inhibition in females when 17β-estradiol levels are elevated. The μ-opioid receptor (MOR) antagonist Cys2,Tyr3,Orn5,Pen7-amide (CTOP; 300 nm) had a similar effect but the d-opioid receptor (DOR) antagonist naltrindole (NTI; 1 μm) did not, implicating MORs in female MF transmission. The GABAB receptor antagonist saclofen (200 μm) occluded effects of CTOP but the GABAA receptor antagonist bicuculline (10 μm) did not. For LTP, a low-frequency (LF) protocol was used because higher frequencies elicited hyperexcitability in females. Proestrous females exhibited LF-LTP but males did not, suggesting a lower threshold for synaptic plasticity when 17β-estradiol is elevated. NTI blocked LF-LTP in proestrous females, but CTOP did not. Electron microscopy revealed more DOR-labeled spines of pyramidal cells in proestrous females than males. Therefore, we suggest that increased postsynaptic DORs mediate LF-LTP in proestrous females. The results show strong MOR regulation of MF transmission only in females and identify a novel DOR-dependent form of MF LTP specific to proestrus. [ABSTRACT FROM AUTHOR]

Androgens have dramatic effects on neuronal structure and function in hippocampus. However, androgen depletion does not always lead to hippocampal impairment. To address this apparent paradox, we evaluated the hippocampus of adult male rats after gonadectomy (Gdx) or sham surgery. Surprisingly, Gdx rats showed increased synaptic transmission and long-term potentiation of the mossy fiber (MF) pathway. Gdx rats also exhibited increased excitability and MF sprouting. We then addressed the possible underlying mechanisms and found that Gdx induced a long-lasting upregulation of MF BDNF immunoreactivity. Antagonism of Trk receptors, which bind neurotrophins, such as BDNF, reversed the increase in MF transmission, excitability, and long-term potentiation in Gdx rats, but there were no effects of Trk antagonism in sham controls. To determine which androgens were responsible, the effects of testosterone metab-olites DHT and 5ɑ-androstane-3ɑ,17ɓ-diol were examined. Exposure of slices to 50 nM DHT decreased the effects of Gdx on MF trans-mission, but 50 nM 5ɑ-androstane-3ɑ,17ɓ-diol had no effect. Remarkably, there was no effect of DHT in control males. The data suggest that a Trk- and androgen receptor-sensitive form of MF transmission and synaptic plasticity emerges after Gdx. We suggest that andro-gens may normally be important in area CA3 to prevent hyperexcitabiiity and aberrant axon outgrowth but limit MF synaptic transmission and some forms of plasticity. The results also suggest a potential explanation for the maintenance of hippocampal-dependent cognitive function after androgen depletion: a reduction in androgens may lead to compensatory upregulation of MF transmission and plasticity. [ABSTRACT FROM AUTHOR]