Human pallial MGE-type GABAergic interneuron cell therapy for chronic focal epilepsy.

Mesial temporal lobe epilepsy (MTLE) is the most common focal epilepsy. One-third of patients have drug-refractory seizures and are left with suboptimal therapeutic options such as brain tissue-destructive surgery. Here, we report the development and characterization of a cell therapy alternative for drug-resistant MTLE, which is derived from a human embryonic stem cell line and comprises cryopreserved, post-mitotic, medial ganglionic eminence (MGE) pallial-type GABAergic interneurons. Single-dose intrahippocampal delivery of the interneurons in a mouse model of chronic MTLE resulted in consistent mesiotemporal seizure suppression, with most animals becoming seizure-free and surviving longer. The grafted interneurons dispersed locally, functionally integrated, persisted long term, and significantly reduced dentate granule cell dispersion, a pathological hallmark of MTLE. These disease-modifying effects were dose-dependent, with a broad therapeutic range. No adverse effects were observed. These findings support an ongoing phase 1/2 clinical trial (NCT05135091) for drug-resistant MTLE.

Rat tickling: A systematic review of applications, outcomes, and moderators.

INTRODUCTION: Rats initially fear humans which can increase stress and impact study results. Additionally, studying positive affective states in rats has proved challenging. Rat tickling is a promising habituation technique that can also be used to model and measure positive affect. However, current studies use a variety of methods to achieve differential results. Our objective was to systematically identify, summarize, and evaluate the research on tickling in rats to provide direction for future investigation. Our specific aims were to summarize current methods used in tickling experiments, outcomes from tickling, and moderating factors. METHODS: We systematically evaluated all articles about tickling identified from PubMed, Scopus, Web of Science, and PsychInfo. Our inclusion criteria were publication in a peer-reviewed journal and collection of original, empirical data on rats using the handling method of tickling. One researcher extracted information from each article. Bias was assessed by 2 investigators using the SYRCLE bias assessment tool. RESULTS: We identified 32 articles (56 experiments) published in peer-reviewed journals about rat tickling for inclusion. A wide variety of strains, sexes, and ages of rats were included. The most common method used for tickling was cycling through 15 seconds of tickling and 15 seconds of rest for 2 minutes for 3 to 5 days. Experiments with a control for tickling (N = 22) showed that tickling increases positive vocalization, approach behavior, decreases anxiety measures, improves handling, and in some cases decreases stress hormones. Tickling juvenile, individually housed rats with a trait predisposition to respond more positively to tickling, results in the most positive outcomes. Methods to reduce bias were insufficiently reported. CONCLUSIONS: We conclude that tickling is a promising method for improving rat welfare and investigating positive affect. However, the establishment of tickling best practices is essential as the outcomes from tickling can be moderated by several factors.