# Notch signaling inhibition attenuates epileptogenesis and hippocampal damage without altering mossy fiber sprouting in adolescent rats post-status epilepticus

## TL;DR

Blocking Notch signaling in rats after a seizure episode reduces brain damage and seizure severity without affecting mossy fiber sprouting.

## Contribution

This study shows that inhibiting Notch signaling post-seizure reduces epileptogenesis and hippocampal damage without altering mossy fiber sprouting.

## Key findings

- DAPT treatment reduced epileptiform discharges and hippocampal neuronal loss in rats.
- Notch inhibition preserved synaptic structure in the hippocampus without affecting mossy fiber sprouting.
- Findings suggest Notch signaling as a potential therapeutic target for post-seizure neuroprotection.

## Abstract

Notch overactivation and aberrant neurogenesis following status epilepticus (SE) has been identified by our previous study. The current study further supplements this by exploring additional pathological changes during epileptogenesis post-SE, as well as the potential role of Notch in these processes.

Rats were administered N-[N-(3,5-difluorophenacetyl)-L-alanyl)]-S-phenylglycine t-butyl ester (DAPT) immediately after SE induction. Spontaneous recurrent seizures were monitored via electroencephalogram (EEG). Hippocampal synaptic ultrastructure was analyzed using transmission electron microscopy. Nissl staining and Timm staining were performed at 28 days post-SE to evaluate neuronal loss and mossy fiber sprouting (MFS), respectively.

EEG recordings demonstrated that DAPT treatment significantly reduced the severity of epileptiform discharges post-SE. Transmission electron microscopy revealed decreased presynaptic active zone length and postsynaptic density thickness in the hippocampal CA1 region of DAPT-treated rats. Nissl staining indicated attenuated hippocampal neuronal loss and partial structural restoration following DAPT administration. Notably, Timm staining showed no significant effect of DAPT on MFS compared to controls.

Inhibition of Notch signaling alleviates EEG epileptic activity, mitigates synaptic damage, and partially preserves hippocampal neuronal structure in adolescent rats post-SE, without altering MFS. These findings suggest Notch signaling as a potential therapeutic target for post-SE neuroprotection, though its role in MFS remains unclear.