Abstract
Objective To explore the effect of conventional whole-brain radiation therapy(WBRT)on the blood-brain barrier (BBB) in rats and provide the experimental basis for the optimum time of clinical chemotherapv after conventional WBRT.Methods 100 Sprague-Dowley rats were randomly divided into five groups,normal control group,10 Gy group,20 Gy group,30 Gy group and 40 Gy group.The rats were exposed to conventional fractionation(2 Gy/day,5 days a week)for a total dose of 10-40 Gy with 60Co γ-rays.MTX(25 ms/kg body weight)were injected intravenously 16 h after each group finished the planned irradiation dosage, and the CSF and blood samples were collected 2 hours later.MTX levels in samples were measured by using RP- HPLC.The changes of ultrastructure of BBB in 4 rats of each group were observed using lanthanum trace labeling with electron microscopy.Results The average concentrations of MTX in rat's CSF in control group,10 Gy group.20 Gy group,30 Gy group and 40 Gy group were 0.068,0.078,0.118,0.236 and 0.229 ms/L, respectively.The MTX concentration in CSF was increasing but not statistically different between the control group and 10 Gy group(P>0.5),so was between the 30 Gy group and 40 Gy group(P>0.5).The MTX concentration difference in CSF between any other two groups was statistically significant(P<0.05).The lanthanum was only seen in the lumens of capillaries but not in the extravessels on the control rats.The lanthanum entered the outside of capillaries but not in the extravesscls in 10 Gy group.It entered the extra cellular space but not the neurons in 20 Gy group,and the plasma, mitochondria and endoplasmic reticulum of neurons in 30 Gy group.For 40 Gy group,lanthanum nitrate particles were observed in the brain tissue diffusely, and a few endothelial cells and neurons lost normal configuration.Conclusions Radiation could directly damage the function and structure of BBB,and the penetration of BBB reaches the peak at 30 Gy,which suggests that it may be a best chemotherapy opportunity after 30 Gy.The limit dose of whole brain radiotherapy is 40 gray,otherwise it may cause irreversible brain injure. Key words: Radiotherapy; Blood-brain barrier; Methotrexate; Ultrastructure; Drug Concentration
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