Functional connectivity within sensorimotor cortical and striatal regions is regulated by sepsis in a sex-dependent manner.

Summary

Using a polymicrobial intra-abdominal sepsis model, the authors show sex-dependent neuroimmune and functional connectivity responses: males exhibit stronger splenic expansion, intracerebral gliosis, and increased intra-striatal connectivity, while females show attenuated network alterations. Both sexes had reduced gut microbiome diversity and recovered body weight by day 7.

Key Findings

• Both male and female mice survived sepsis, regained body weight by 7 days, and showed reduced gut microbiome diversity.
• Post-septic males exhibited stronger splenic cell expansion and intracerebral glial proliferation compared with females.
• Resting-state fMRI showed increased intra-striatal connectivity in males, with female mice maintaining near-baseline intra-striatal connectivity and reduced alterations in PAG→SC and ACC–striatal projections.

Clinical Implications

While preclinical, findings argue for incorporating sex as a biological variable in neurocognitive assessment and rehabilitation after sepsis, and motivate clinical fMRI studies to identify at-risk survivors (particularly males) for tailored interventions.

Limitations

• Preclinical murine model limits direct generalizability to humans; exact sample sizes per group are not specified in the abstract.
• Functional connectivity changes were not linked to behavioral outcomes or causal neural manipulations.

Future Directions

Couple rs-fMRI with behavioral testing and causal circuit manipulations; dissect hormonal and microglial drivers of sex differences; translate to longitudinal clinical neuroimaging in sepsis survivors.