# From Acute Stress to Long-Term Dysregulation: Changes in Hematological and Hormonal Parameters in the Long-Term Post-Stress Period in a Modified SPS&S Model

## TL;DR

This study introduces a modified PTSD model in rats that captures long-term stress effects through behavioral and physiological changes.

## Contribution

A modified SPS&S model is proposed to better replicate PTSD progression with stable biomarker changes over time.

## Key findings

- 25% of rats developed a PTSD-like phenotype with persistent biomarker alterations.
- PTSD rats showed increased anxiety, neutrophilic leukocytosis, and endocrine dysregulation.
- Stress markers remained stable for 28 days post-stress, indicating long-term dysregulation.

## Abstract

Objectives: Existing animal models of post-traumatic stress disorder (PTSD) are often methodologically complex and produce variable outcomes. The aim of this study was to develop a modified PTSD model that accurately recapitulates the clinical progression of the disorder, incorporating both behavioral features and objective physiological parameters. Methods: We utilized a modified Single Prolonged Stress with Subsequent Stress (SPS&S) protocol, supplemented by a stress reminder phase (without re-exposure to primary stressors) and an evaluation of stress response extinction. Eighty male Wistar rats were subjected to the stress protocol, followed by comprehensive behavioral, hematological (leukocytes, hemoglobin, and hematocrit), and hormonal (corticosterone; adrenocorticotropic hormone (ACTH)) assessments 4–5 weeks post-stress. Results: The model produced a PTSD-like phenotype in 25% of animals, characterized by persistent alterations in the investigated biomarkers. The PTSD group exhibited sustained behavioral impairments (increased anxiety), hematological changes (neutrophilic leukocytosis), and endocrine dysregulation (decreased corticosterone, ACTH, and epinephrine). Conclusions: This modified SPS&S model demonstrates validity for studying the long-term consequences of stress, with PTSD markers remaining stable throughout the 28-day observation period.