| Due to the rapid development of society and the progress of medical and health conditions,the aging of the population has aggravated,which leads to the high incidence of central nervous system(Central Nervous System,CNS)diseases,CNS diseases mainly including meningitis,stroke,Alzheimer’s disease and other diseases.The main reason for the high incidence of CNS disease and poor treatment effect is the existence of the Blood-Brain Barrier(BBB).Due to the tight structure of the BBB,drugs exceeding 500 Da cannot enter the brain parenchyma.The function of BBB not only sustains the stability of the CNS system,but also restricts drug access to the brain parenchyma.The approaches of opening the BBB has also been explored.The ideal method of opening the BBB should be non-invasive,reversible,safe and easy to operate.Electromagnetic Pulses(EMP)opening the BBB has been proven to be non-invasive,reversible and easy to operate.Therefore,this article explores the law and mechanism of EMP inducing BBB opening.This article explores the laws of EMP’s different field intensity,pulse number and pulse width on the BBB permeability of the rat brain.The Evans blue(EB)tracer method was used to investigate the change of BBB permeability under different field intensitys,and a regular curve was obtained.In addition,the regular curves of different pulse numbers and BBB opening under the field intensities of 200 k V/m and 400 k V/m are studied.Finally,the effects of three different pulse widths of 200 k V/m,200 ns and 250 k V/m,120 ns and 720 k V/m,20 ns of EMP on the permeability of rat BBB were explored.The results showed that with the increase of EMP field intensity,the permeability of rat BBB also increased,and there were significant differences between 200 k V/m and 400 k V/m compared with the sham-irradiated group.The EB leakage value of 400 k V/m group is 2.6 times that of the sham-irradiation group.When the pulse width is 200 ns and the number of pulses increases,the permeability of the rat BBB first increases and then decreases,reaching a peak at200 pulses.When the pulse width is 120 ns and the pulse increases,the permeability of BBB also increases first and then decreases,but the peak point is the number of pulses 1000.Field intensity of 250,200 k V/m,pulse width of 120,200 ns can induce BBB to open,but pulse width of 20 ns cannot open BBB.In order to better understand the regular changes of EMP opening BBB,this article also explored the mechanism of EMP inducing BBB opening.By detecting the expression of Tight Junction(TJ)protein,exploring the changes in the m RNA content of TJ protein after EMP irradiation,and observing the characteristics of different molecular weight tracers passing BBB and the ultrastructure of BBB.The experimental results of protein and m RNA showed that the expression levels of TJ protein and PKC isoenzyme-related protein and RNA did not change significantly under different field intensities and different pulse numbers.The BBB ultrastructure observation results show that as the field intensity increases,the TJ channel gap enlargess,and as the number of pulses increases,the TJ channel also raises.The results of this paper show that the law of BBB opening induced by EMP is: 1)With the increase of field intensity,the degree of BBB opening also increases.2)As the field intensity enlarges,the degree of BBB opening first magnifies and then decreases,showing a "window effect".3)There is a threshold relationship between pulse width and BBB permeability.FITCdextran of different molecular weights through BBB,WB,q RT-PCR and TEM results show that the potential mechanism of EMP-induced BBB opening is: EMP irradiation did not cause a significant change in TJ protein expression and its corresponding m RNA content,but caused TJ channel gap increases,and the passage of substances through the BBB is molecular size dependent. |
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