Single nucleus sequencing of mouse hippocampi four days after pilocarpine induced status epilepticus

All current drug treatments for epilepsy, a neurological disorder affecting over 50 million people merely treat symptoms, and a third of patients with epilepsy do not respond to medication. There are no disease modifying treatments that may be administered briefly to patients to enduringly eliminate spontaneous seizures and reverse cognitive deficits. Applying network approaches to whole tissue and single-nuclei transcriptomic data collected from mouse models of temporal lobe epilepsy and publicly available transcriptomic data from human temporal lobectomy samples, we confirmed a previously described pattern of rapid and transient induction of the Janus kinase/signal transducers and activators of transcription (JAK/STAT) pathway within days of epileptogenic insult. This was followed by a resurgent activation weeks to months later with the onset of spontaneous seizures. Targeting the first wave of JAK/STAT activation after epileptic insult did not prevent seizures. However, inhibition of..., Pilocarpine model of status epilepticus. Status epilepticus was induced in male and female C57BL/6CRN mice with pilocarpine (8-12 weeks old). Mice were injected with terbutaline (4 mg/kg i.p., Sigma T2528) and methylscopolamine (4 mg/kg ip, Sigma S8502) to alleviate respiratory and cardiovascular effects of pilocarpine, then 30 min later received saline or pilocarpine (280 mg/kg i.p. as free base, Sigma P6503). After 1 hour of SE, seizures were interrupted by diazepam (10mg/kg i.p.). Mice were weighed and scored for behavioral deficits (Irwin score) daily, with injections of lactated Ringer’s solution as needed.
Tissue Harvest and Sequencing. To select which epileptic mice would be sent for sequencing, we determined a composite score of seizure severity during pilocarpine SE, weight loss 24 hours after SE, ability to build a nest and neurobehavioral recovery scores on day 4 after SE (See Fig. S14 in linked manuscript Hoffman et al). The mean number of standard deviations from the mean o..., , # Single nucleus sequencing of mouse hippocampi four days after pilocarpine induced status epilepticus

[https://doi.org/10.5061/dryad.kprr4xhg7](https://doi.org/10.5061/dryad.kprr4xhg7)

## Description of the data and file structure

All current drug treatments for epilepsy, a neurological disorder affecting over 50 million people merely treat symptoms, and a third of patients with epilepsy do not respond to medication. There are no disease modifying treatments that may be administered briefly to patients to enduringly eliminate spontaneous seizures and reverse cognitive deficits. Applying network approaches to mouse models of temporal lobe epilepsy and human temporal lobectomy samples at both whole tissue and single-nuclei resolutions, we observe the well-characterized pattern of rapid induction and subsequent quenching exhibited of the JAK/STAT pathway within days of epileptogenic insult. This is followed by a resurgent activation weeks to months later with the onset of spontaneous s...