Objective: To explore the impairment mechanisms of blood brain barrier in spinal cord and observe the changes of matrix metalloproteinase-9 (MMP-9) and functional improvement in rats with chronic fluorosis.
Methods: A total of 120 Wistar rats were divided randomly into 4 groups, high fluoride (fed by water with a high concentration of sodium fluoride at 200 mg/L), high fluoride control (fed by distilled water), defluorination (fed by water with a high concentration of sodium fluoride at 200 mg/L for 12 weeks and then distilled water for 12 weeks) and defluorination control (n = 30 each). The urinary contents of fluoride were detect for 4 groups at Weeks 4, 8 and 12. The high fluoride and control groups were sacrificed at Week 12 while the defluorination and defluorination control groups at Week 24. Their cervical spinal cords were collected for electron microscope examinations. The expression of MMP-9 protein in thoracic cord was detected by immunohistochemistry and Western blot. Quantitative analysis of function of blood brain cord barrier was performed by the technique of Evans blue. The comparison of measurement data was performed with F test and correlation analysis. The cytological changes of neurons in thoracic spinal cord were detected after chronic fluorosis.
Results: Under electron microscope, the pathological manifestations of chronic damage in blood brain barrier could be found. As compared with the high fluoride control group, the content of Evans blue increased markedly in spinal cord of the high fluoride group (29.2 ± 0.1 vs 0.7 ± 0.1 mg/L, P < 0.01). It was higher in the defluorination group than that in the defluorination control group. But there was no significant difference with the high fluoride group (29.2 ± 0.1 vs 28.9 ± 0.2 mg/L, P > 0.01). And the expression of MMP-9 increased in spinal cord of the fluorosis and defluorination groups in comparison with those in the control group. But no difference existed among them.
Conclusion: The damage of blood brain barrier of spinal cord occurs probably as a result of a higher expression of MMP-9 in rats with chronic fluorosis. Defluorination for a short time may not recover.