# A Novel NLRP3 Inhibitor AMS‐17 Rescues Deficits in Long‐Term Potentiation Following Mild Traumatic Brain Injury in Adult C57Bl/6 Mice

## TL;DR

A new NLRP3 inhibitor called AMS-17 helps restore brain function in mice after mild traumatic brain injury by reducing harmful inflammation.

## Contribution

AMS-17 is a novel NLRP3 inhibitor shown to rescue synaptic plasticity deficits after mTBI in mice.

## Key findings

- mTBI caused long-term potentiation deficits in mice that developed by 3 days post-injury.
- AMS-17 incubation restored LTP to sham-injured levels without affecting healthy mice.
- Targeting NLRP3 may be a promising treatment for mTBI-related cognitive impairments.

## Abstract

Traumatic brain injury (TBI) is a leading cause of long‐term disability, with limited effective treatment options. A key factor of TBI pathophysiology is neuroinflammation, which can involve the activation of the nucleotide‐binding domain leucine‐rich repeat protein 3 (NLRP3) inflammasome. Aberrant inflammation following injury has the ability to reduce the capacity to induce long‐term changes in synaptic plasticity, a leading mechanism for the development of learning and memory deficits following injury. This study investigated the potential of a novel NLRP3 inhibitor, AMS‐17, to mitigate synaptic plasticity deficits following mild TBI (mTBI) in mice. Adult C57Bl/6 mice were subjected to mTBI or a sham injury, and hippocampal slices were then prepared for field electrophysiological recordings in the medial perforant pathway of the dentate gyrus. We found that mTBI induced deficits in long‐term potentiation that were not immediate at 2 h post‐injury but developed by 3 days post‐injury. We next incubated slices in AMS‐17 or a control solution prior to electrophysiological recordings. Here we found that incubation with AMS‐17 rescued these LTP deficits, bringing them to levels observed in sham‐injured controls. Importantly, AMS‐17 did not affect the capacity to induce LTP in sham‐injured mice. These findings suggest that targeting the NLRP3 inflammasome may offer a promising therapeutic strategy to reduce learning and memory impairments following mTBI. Further studies are needed to determine the optimal therapeutic window and long‐term efficacy of AMS‐17 in mTBI.