# Slow Releasing CO Donor Modulates Susceptibility to Seizures in Rats with Chronic Prostatitis/Chronic Pelvic Pain Syndrome: Behavioral and EEG Study

## TL;DR

A CO-releasing molecule reduced seizure risk in rats with chronic prostatitis, suggesting a potential new treatment approach.

## Contribution

Demonstrates that CORM-A1 reduces seizure susceptibility in a rat model of CP/CPPS.

## Key findings

- CORM-A1 treatment decreased seizure incidence, latency, and severity in CP/CPPS rats.
- CORM-A1 reduced the number and duration of ictal periods in CP/CPPS animals.
- CP/CPPS increased seizure risk compared to sham controls.

## Abstract

Background and Objectives: Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a complex disease that involves changes in multiple organs and even the central nervous system (CNS). CP/CPPS may elevate seizure risk via neuroinflammatory mechanisms within the CNS. Neuroprotective effects of CO-releasing molecules (CORMs) were demonstrated in inflammation-driven conditions, while CORMs potential to ameliorate seizure susceptibility in inflammatory states, like CP/CPPS, remains unclear. Therefore, we investigated effects of CORM-A1 on susceptibility to lindane–induced seizures in rats with CP/CPPS through behavioral and electroencephalographic (EEG) study. Materials and Methods: Wistar rats were divided into four groups (n = 8/group): Sham-PBS, Sham-CORM, CP/CPPS-PBS and CP/CPPS-CORM. The CP/CPPS model was created by injection of 3% λ-carrageenan and its development assessed by mechanical pain threshold. CORM-A1 (2 mg/kg/day, i.p.) or vehicle (PBS) was given during seven postoperative days. Hereupon, subconvulsive dose of lindane (4 mg/kg, i.p.) was administered and behavioral features of seizures were observed alongside with EEG recordings. Results: Our data showed that the incidence and severity of lindane-induced seizures was significantly higher in the CP/CPPS-PBS group than in the Sham-PBS group. CORM-A1 treatment significantly decreased seizure incidence, prolonged seizure latency, and reduced seizure severity in CP/CPPS rats compared to vehicle treatment (CP/CPPS-CORM vs. CP/CPPS-PBS). Also, CORM-A1 treatment significantly reduced the number and duration of ictal periods induced by lindane in CP/CPPS animals compared to vehicle treatment. Conclusions: It could be concluded that CORM-A1 treatment reduced both behavioral and EEG signs of increased seizure susceptibility in rats with CP/CPPS, thus it could be a potential therapeutic target.