Study On The Effect Of Electromagnetic Pulse On The Permeability Of Blood-brain Barrier In Rabbits

The existence of the blood-brain barrier（BBB）brings challenges to the treatment of central nervous system（CNS）diseases.Opening the BBB by electromagnetic pulse（EMP）becomes a potential treatment for CNS diseases due to its reversibility,non-invasiveness,and small side effects.At present,the experimental studies of BBB opening induced by EMP exposure are mainly in rats and mice.The difference in electric field intensity in rat brains caused by the diversity of irradiation parameters makes it incompatible with different experimental studies,let alone extrapolating these experimental results to the human body.The intracerebral electric field is the key physical quantity concerned with the EMP-induced biological effects.Therefore,it is necessary to systematically study the intracerebral field of different types of animals under different EMP irradiation parameters,to search for patterns to allow extrapolation to human cases referring to animal experiments.Therefore,based on the experimental results of rats,we further studied the relationship between EMP irradiation and BBB opening of a relatively larger animal—rabbits.Firstly,the intensity of electric field in rabbit brain was obtained by numerical simulation;Subsequently,the relationship between EMP parameters and rabbit BBB opening was studied experimentally;Finally,the law of influence of EMP irradiation on BBB opening in both rabbits and rats was discussed referring to the intracerebral electric field,and the reference intensity of the electric field of EMP that required for BBB opening in pigs,monkeys,and humans was recommended.This work is expected to provide theoretical reference and data support for the preclinical study on EMP-induced BBB opening.In this paper,a three-dimensional digital model of rabbits was constructed based on 7T-MRI,and the EMP irradiation chamber was established.The three-pole Debye model was used to describe the dielectric parameters of biological tissues,and the intracerebral electric field was calculated by Xfdtd.The calculation results showed that:（1）The pulse width of the penetrated EMP within the rabbit brain was greatly narrowed when compared to the original waveform;（2）The change of irradiation parameters will affect the field strength of the penetrated EMP in the brain.The intensity of the electric field reached a maximum at E-polarization（the direction of the animal body length is consistent with the electric field of the wave）,decreased at k-polarization（the direction of the animal body length is consistent with the wave vector）,and reached a minimum at H-polarization（the direction of the animal body length is consistent with the magnetic field of the wave）.The steeper the pulse front is,the stronger the intracerebral field is,and the weaker the influence of the pulse width on the intracerebral field is;（3）Under the same external field of the incident EMP,the field strength in the brain of rabbits is nearly doubled from that of rats.The experimental results of EMP-induced BBB opening in rabbits showed that:（1）The polarization direction affects the permeability of rabbit BBB.Under the same irradiation field,the Evans Blue leakage of rabbits brain under the k-polarization was significantly different from that of the Sham group,but there was no significant difference in H polarization.This is because the intracerebral field in the case of k-polarization is greater than that of H-polarization;（2）The number of pulses also affected the BBB opening of rabbits.It showed that with the increase in pulse number,the permeability of rabbit BBB firstly increased and then decreased,and reached a maximum at the pulse number of 200;（3）With the increase of EMP field strength,the permeability of rabbit BBB increased.The experimental results of tracers with different molecular weights（EB and FITC-dextran）showed that EMP-induced BBB opening in rabbits has a size effect.The stronger the irradiation field strength is,the bigger the molecular weight of the tracer that can pass through the BBB.It is found that the law of influence of pulse number and irradiation field intensity on BBB permeability of the rabbits is largely in line with that of rats.Similar intracerebral field leads to approximate BBB effects within such two types of animals.Therefore,we regard that the intracerebral field can be used to better explain the law of EMP-induced BBB opening.Subsequently,the intracerebral field strength of pigs,monkeys,and humans was calculated to estimate the reference electric field intensity of EMP required for their BBB opening,which could provide a reference for the follow-up studies on large animal experimental.