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Optimized Mouse Model of Sepsis-Associated Encephalopathy: A Rational Standard Based on Modified SHIRPA Score and
Yuewen Xin1, Mi Tian1, Xu Pei1
1Department of Critical Care Medicine of Huashan Hospital, State Key Laboratory of Medical Neurobiology, MOE Frontiers Center for Brain Science and Institutes of Brain Science, Fudan University, Shanghai, China.
CNS Neuroscience & Therapeutics
|April 9, 2025
Summary
This study introduces a standardized method to diagnose sepsis-associated encephalopathy (SAE) in mice. Using a median score approach, it effectively differentiates neurological impairment in SAE models.
Area of Science:
- Neuroscience
- Immunology
- Pathology
Background:
- Sepsis-associated encephalopathy (SAE) causes severe brain dysfunction.
- Current diagnostic criteria for SAE in animal models are inconsistent.
- A standardized evaluation method for SAE in mice is needed.
Purpose of the Study:
- To develop and validate a standardized method for diagnosing SAE in murine models.
- To improve the differentiation between SAE and non-SAE in research settings.
- To facilitate a better understanding of SAE pathogenesis and treatment.
Main Methods:
- Induction of sepsis using the cecal ligation and puncture (CLP) model in mice.
- Assessment of physiological status with a modified SHIRPA score, categorized by median split.
- Validation through behavioral tests (Y-maze, social interaction, open field), neuroinflammation markers, neuronal damage assessment, Morris water maze, and hippocampal LTP.
Main Results:
- Conventional SHIRPA grading was insufficient for SAE differentiation.
- The median-split modified SHIRPA score effectively distinguished neurological impairments.
- Mice with higher scores showed increased neuroinflammation, neuronal injury, and cognitive deficits.
Conclusions:
- A reliable evaluation method for SAE in murine models has been established.
- This method enhances the differentiation between SAE and non-SAE.
- Advancements will improve SAE pathogenesis understanding and inform treatment strategies.
