Protective Effect Of Fucoidan On Hypoxic-Ischemic Brain Damage In Neonatal Rats

Objective: Hypoxic-ischemic encephalopathy (HIE) is a kind of newborn disease, which is one of the most common causes of severe brain damage, neonatal death and long-term neurological deficits in children. The pathogenetic machanism of HIE is complex. Many associated factors interact each other and contribute to the neuropathologic lesions and neurodevelopmental disabilities. It is very important to find out some effective neuroprotective strategies to improve the prognosis of HIE. Fucoidan extracted from brown algae is a marine sulfated polysaccharide endowed with important biological properties, such as anticoagulant and antithrombotic activity, antiadhesive activity, anticomplementary activity and promoting revascularization. It has been reported that fucoidan can inhibit the development of organ injury by ischemia and reperfusion (I/R) in heart, renal, limb and brain. In this study, whether fucoidan has protective effect on hypoxic-ischemic brain damage in neonatal rats has been investigated.. Method: The HIBD model was performed with seven-day-old SD rats. Briefly, after the left common carotid artery had been cut animals were exposed to a gas mixture of 8% oxygen and 94% nitrogen. All rats were divided into five groups at random:â… . preventive group, 13 rats (just before starting hypoxic exposure, they were injected intraperitioneally with fucoidan 0.25ml/10g);â…¡. therapeutic group, 13 rats (after hypoxic exposure, they were injected intraperitioneally with fucoidan 0.25ml/10g);â…¢. Twice administer group, 13 rats (before and after hypoxic exposure, they were injected respectively with fucoidan 0.125ml/10g);â…£. contral group, 12 rats (after hypoxic exposure, they were injected intraperitioneally with saline 0.25ml/10g);â…¤. sham operated group, 5 rats (their left common carotid artery just was isolated, without hypoxia). Seven pups of â… to â…£groups were killed four days after the administration of HI injury. After tissue preparation, TUNEL and H-E staining was performed to evaluate CA1 neuronal loss and apoptotic neuronal cell death. When the left pups were fifty days old, Morris water maze including hidden-platform acquisition training and probe trial testing was performed to investigate whether fucoidan can minimize long-lasting functional deficits. Result: The study show that the number of TUNEL-positive cells in the hippocampus and average neuronal loss in the CA1 decreased significantly in the groups that has received fucoidan compared with the contral group. In the hidden-platform acquisition training, the escape latency time of HI animal (group â… ,â…¡,â…¢versus group â…£) is shortened significantly. In probe trial testing the average searching time and distance of preventive group and twice administer group are longer than that of contral group significantly. However, neither in the cell counting nor in the Morris water maze the difference between any two groups of all that received fucoidan reached statistical significance. Conclusion: Our results suggest that fucoidan can alleviate HI insult in the immature brain by decreasing both apoptosis and CA1 neuronal loss and mininize long-lasting functional deficits by ameliorate spatial learning and memory.