Vitamin D intervention improves recognition memory and reduces hippocampal inflammation in rats submitted to an experimental model of cerebral palsy

Abstract

Cerebral Palsy (CP) comprises neurological conditions characterized by abnormalities in movement, body posture, and altered muscle tone. Vitamin D (VitD) is important in bone metabolism and has anti-inflammatory, immune, and neuromodulatory properties. The aim of this study was thus to investigate the effects of VitD supplementation on parameters associated with memory, hippocampal inflammation, and neuronal loss in male and female rats with CP. The experimental model of CP included postnatal anoxia (P0-P1) and sensory-motor restriction (P2-P28). The pups were treated intraperitoneally with vehicle or VitD (5 μg/kg/day) during the first 30 days of postnatal life. The following were assessed: reflex-ontogeny, T-Maze and novel object recognition test (NORT), glial and neuronal responses, and inflammatory markers in the hippocampus. In male pups, CP caused delayed reflex maturation, impaired short- (P31) and long-term (P38) object recognition and spatial memory (P50-P52), reduced neuronal density, increased microglial area and density, and elevated expression of tumor necrosis factor alpha (TNF-α) and interleukin-6 (IL-6). Female CP pups showed only delayed reflex maturation, impaired long-term object recognition, and increased microglial area. Intervention with VitD led to an earlier maturation of the righting reflex in males and females with CP, better performance in object recognition in the long term, a reduction in the area and density of microglia, as well as a reduction in the expression of TNF-α and IL-6 in CP males. These results confirm the greater resilience of females to the damage caused by CP and the promising effects of VitD in reducing hippocampal neuroinflammation.