Intracranial LPS injection induces cerebral palsy-like motor and behavioral deficits in immunodeficient mice

The translational potential of human cell therapies for cerebral palsy (CP) is limited by a lack of immune-compatible preclinical models. To address this, we established a CP-like model via intracranial lipopolysaccharide (LPS) injection in neonatal immunodeficient mice. Compared to Sham controls (n = 12), LPS-injected mice (n = 12) exhibited lower survival (83.3% vs. 100%), reduced body weight (23.15 ± 2.07 g vs. 25.53 ± 0.99 g, P < 0.01), and significant motor deficits, including locomotor asymmetry, impaired balance, and hypolocomotion. Gait analysis revealed hindlimb-predominant spatiotemporal abnormalities: prolonged stance, propulsion, and swing durations; reduced stride frequency and stance width; and a divergent forelimb-hindlimb paw angle response. These findings demonstrate that intracranial LPS injection in immunodeficient mice produces a multifaceted CP‑like phenotype featuring hindlimb-predominant gait abnormalities, motor incoordination, and altered exploration. This model could serve as a validated, immune-compatible platform for studying CP pathophysiology and for the preclinical evaluation of human cell therapies.