Optimized Mouse Model of Sepsis‐Associated Encephalopathy: A Rational Standard Based on Modified SHIRPA Score and Neurobehaviors in Mice

ABSTRACT Background Sepsis‐associated encephalopathy (SAE), a severe neurological disorder, is marked by widespread brain dysfunction. At present, there is no universally accepted criterion for diagnosing SAE in animal models. This study proposes a standardized evaluation method for SAE in mice, addressing inconsistencies in current research. Method Using a cecal ligation and puncture (CLP) model to induce sepsis, we assessed the physiological status of mice with a modified SHIRPA score to differentiate SAE from non‐SAE, validating our findings through various behavioral tests and evaluations of neuroinflammation and neuronal damage. Results Our findings revealed that the conventional mild–moderate–severe categorization of SHIRPA was insufficient for distinguishing between SAE and non‐SAE. To enhance differentiation, we classified mice based on the median modified SHIRPA score, validating this approach through behavioral tests including the Y‐maze, three‐chamber social test, and open field test. This method effectively identified neurological impairments in septic mice. Further validation involved assessing neuronal damage, neuroinflammation, the Morris water maze, and long‐term potentiation (LTP) in the hippocampal CA1 region. Results indicated that mice in the up‐Median group exhibited greater neuroinflammation, neuronal injury, and cognitive deficits compared to the down‐Median group. Conclusions This study establishes a reliable evaluation method for SAE in murine models, facilitating improved differentiation between SAE and non‐SAE. Such advancements will enhance our understanding of the pathogenesis of SAE and guide more effective treatment strategies.