The Role Of BBB In Immune Molecules-Brain Communication And The Change Of The Brain Neuron Activity Induced By Superantigen SEB

This thesis comprises two parts. One is about the effect of the blood- brain barrier (BBB) opening induced by adrenaline (AD) on the cerebral immune condition and the function of neuroimmunomodulation, the other is about the possible type of the brain modulation to the immune activity induced by the sttperantigen staphylococcal enterotoxin B (SEB). Central nervous system (CNS) is considered as an immune privilege tissue mainly owing to the existence of BBB. Because of the selective permeability to the substance of both sides, BBB maintains the stability of normal structure and function of CNS as well as limits the immune molecular or cells in the plasma. However, BBB opening under various conditions may leads the plasma substance enter the brain which can not pass the BBB normally, which offers an opportunity for the immune signal molecules reaching the brain and for the change of the privilege of the brain. Of all the factors to BBB, blood pressure is the common and sensitive one. This research investigated the relation between the BBB opening by transient hypertension induced by adrenaline administration and the plasma ?? 第四军医大学博士学位论文一proteins enteringthe brain．Firstly,we applied Evansblue to examinetheopeningofBBB inthe ratwith tluorescence microscope,whichimprovedthe sensitivityofthe BBB openingevaluation．Itwasfoundthatthe brainareas where BBB opened by AD were patch－like,and the number of＊thepatches mightbe used asthe evaluation to he degree ofBBB opening．Secondly,With the aid of this method,the effect of transient hypertensionon BBB opening by various doses ofAD was investigated．The detection ofthe rats'咖erial pressure and the observationic the BBB opening inthebrain sections showed that in a certain range BBB opened by transienthypertension with atime－and amplitude－dependent mariner,and theopeningthreshold was obtained．Then we testthe rat BBB opening by thetransient hypeftension underthe openingtNesholdwith pretreatment oflipopolysacchride(LPS)administration．The result showing the rat's BBBopened mildly implicated irrunune challenge may increase the vulnerabilityofBBB so asto provide an condition forthe immune signal molecularentering the brain． On the other hand,BBB opening caused immune effective molecular inplasma entrance to the brain also challenged the normal immune situation ofhe CNS．In this aspect,this part also discussed whether the immuneglobulin G(IgG)could cross BBB on BBB opening by transienthypertension．With the methods of immunohistochemistry,electricalmicroscope and Westemblot,we provedthatwhenBBB openedbytransient hypeftension,the plasma IgG crossed BBB and entered thecerebral tissue．Andthe routoflgG was observed as from the caPillary tothe endothelial cellularplasma,thento the spacebetweenthe neurons' 一6一 projections. These data suggested that some anti-encephaloantigen antibodies should enter the brain when peripheral antibody titer was increased by immune reaction, and lead to CNS immune damage. Thus would be a possible mechanism of some CNS autoimmune disease pathogenesis. In the second part, it was investigated that the possible brain area modulating the peripheral immune activity induced by superantigen (Sag) staphylococcal enterotoxin B (SEB) and the role of p44/42 MAPK in the modulation. SAg is a type antigen characteristic with binding to both MHC II molecular and T cell receptor V 13 motif so...