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Sex differences in memory impairments after traumatic brain injury: mechanisms and models
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DOI：10.3389/fnbeh.2026.1874990.png)
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Abstract
En 中文
Traumatic brain injury (TBI) is a major cause of long-term cognitive impairment; with deficits in episodic memory among the most common and disabling consequences. Although biological sex is increasingly recognized as an important determinant of TBI outcomes; its role in shaping post-injury memory impairment remains incompletely understood. Findings from both clinical and preclinical studies are often inconsistent; and sex is frequently underrepresented in experimental designs. Clinical studies generally indicate that women experience worse cognitive outcomes after TBI; including more severe and persistent memory deficits and greater affective burden. In contrast; preclinical findings are more variable; with sex differences emerging in a domain-specific and context-dependent manner. Early animal studies often reported no significant sex differences; particularly in spatial memory tasks. More recent work reveals that males tend to show earlier and more widespread spatial learning impairments and greater vulnerability to anterograde memory deficits; while females more commonly exhibit delayed but persistent deficits in memory consolidation and retention. These behavioral differences are accompanied by sex-specific mechanisms. Altogether; sex differences in memory outcomes following TBI are complex; context-dependent; and shaped by both biological and methodological factors. Greater incorporation of sex as a biological variable in both clinical and preclinical research is essential. Moving toward a precision medicine framework; accounting for sex as a variable in therapeutic target selection and trial design will be important for optimizing cognitive recovery after TBI.
Keywords:
sex
memory
females
traumatic brain injury
preclinical models
males
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