Neonatal quercetin exposure reduces motor impairments and cerebellar damage in cerebral palsy rats, with different effects on males and females.

Abstract

Cerebral palsy (CP) comprises a group of neuromusculoskeletal disorders resulting from fetal or infant brain injury. Quercetin has demonstrated antioxidant, anti-inflammatory and neuroprotective properties in neurological diseases. This study aimed to evaluate the effects of neonatal treatment with quercetin on motor development, neuronal loss, and inflammation in the cerebellum of rats subjected to CP. CP model was induced by postnatal anoxia (P0 and P1) and hindlimbs sensorimotor restriction (P2 to P28). Quercetin (10 mg/kg) was administered intraperitoneally from P2 to P22. Animals were analyzed for somatic growth; reflex ontogenesis; muscle strength; motor coordination; locomotor activity and gait in CatWalk; neuronal loss and inflammation in the cerebellum. Experimental CP, regardless of sex, restricted body weight gain, somatic growth, soleus muscle weight, muscle strength, motor coordination, locomotor activity and gait development, and promoted increased neuroinflammation in the cerebellum. Neonatal quercetin exposure was positive in the model of CP in males, favoring body weight gain, reducing the presence of primitive reflexes, increasing muscle strength, improving exploratory capacity in the open field, decreasing the time in the swing phase during gait, and reducing the expression of TNF in the cerebellum. In females, quercetin had a protective effect by stimulating somatic growth, favoring the regularity of steps during gait, and preventing neuronal loss in the cerebellum of CP animals. This study suggests a greater responsiveness in males compared to females, and indicates a possible protective role of quercetin in both sexes in motor development and neuroinflammation in CP models.