RESUMEN
Cerebral palsy (CP) is a neurodevelopmental disorder characterized by motor and postural impairments. However, early brain injury can promote deleterious effects on the hippocampus, impairing memory. This study aims to investigate the effects of resveratrol treatment on memory, anxiety-like behavior, and neuroinflammation markers in rats with CP. Male Wistar rats were subjected to perinatal anoxia (P0-P1) and sensory-motor restriction (P2-P28). They were treated with resveratrol (10 mg/kg, 0.1 ml/100 g) or saline from P3-P21, being divided into four experimental groups: CS (n = 15), CR (n = 15), CPS (n = 15), and CPR (n = 15). They were evaluated in the tests of novel object recognition (NORT), T-Maze, Light-Dark Box (LDB), and Elevated Plus Maze (EPM). Compared to the CS group, the CPS group has demonstrated a reduced discrimination index on the NORT (p < 0.0001) and alternation on the T-Maze (p < 0.01). In addition, the CPS group showed an increase in permanence time on the dark side in LDB (p < 0.0001) and on the close arms of the EPM (p < 0.001). The CPR group demonstrated an increase in the object discrimination index (p < 0.001), on the alternation (p < 0.001), on the permanence time on the light side (p < 0.0001), and on the open arms (p < 0.001). The CPR group showed a reduction in gene expression of IL-6 (p = 0.0175) and TNF-α (p = 0.0007) and an increase in Creb-1 levels (p = 0.0020). The CPS group showed an increase in the activated microglia and a reduction in cell proliferation in the hippocampus, while CPR animals showed a reduction of activated microglia and an increase in cell proliferation. These results demonstrate promising effects of resveratrol in cerebral palsy behavior impairment through reduced neuroinflammation in the hippocampus.
RESUMEN
BACKGROUND: Different approaches to reproduce cerebral palsy (CP) in animals, contribute to the knowledge of the pathophysiological mechanism of this disease and provide a basis for the development of intervention strategies. Locomotion and coordination are the main cause of disability in CP, however, few studies highlight the quantitative differences of CP models, on locomotion parameters, considering the methodologies to cause brain lesions in the perinatal period. METHODS: Studies with cerebral palsy animal models that assess locomotion parameters were systematically retrieved from Medline/PubMed, SCOPUS, LILACS, and Web of Science. Methodological evaluation of included studies and quantitative assessment of locomotion parameters were performed after eligibility screening. RESULTS: CP models were induced by hypoxia-ischemia (HI), Prenatal ischemia (PI), lipopolysaccharide inflammation (LPS), intraventricular haemorrhage (IVH), anoxia (A), sensorimotor restriction (SR), and a combination of different models. Overall, 63 studies included in qualitative synthesis showed a moderate quality of evidence. 16 studies were included in the quantitative meta-analysis. Significant reduction was observed in models that combined LPS with HI related to distance traveled (SMD -7.24 95 % CI [-8.98, -5.51], Z = 1.18, p < 0.00001) and LPS with HI or anoxia with sensory-motor restriction (SMD -6.01, 95 % CI [-7.67, -4.35], Z = 7.11), or IVH (SMD -4.91, 95 % CI [-5.84, -3.98], Z = 10.31, p < 0.00001) related to motor coordination. CONCLUSION: The combination of different approaches to reproduce CP in animals causes greater deficits in locomotion and motor coordination from the early stages of life to adulthood. These findings contribute to methodological refinement, reduction, and replacement in animal experimentation, favoring translational purposes.