Study On Treatment Of AD Rats By Anti-Aβ Antibody Vianasal Administration

IntroductionAlzheimer's disease is a kind of recognition defect clinical syndrome with special cerebral pathological change. AD often occurs in the aged. At present, it has become the forth cause of death behind heart disease, tumor and stroke.The main pathological characters are senile plaque, neurofibrillary tangle and loss of basal forebrain cholinergic neurons. Among these, the major component of senile plaque isβ-amyloid protein. The etiology of AD is poorly understood, however accumulation of Aβis likely to play an early role in AD pathogenesis. So the therapeutic measure aim at Aβwill become a potential treatment.Blood brain barrier prevents most exogenous macromolecule enter cerebral parenchyma from blood circulation. Nasal administration is a new central nervous system medication method, which can directly deliver drugs to CNS bypassing the BBB. It has the characteristic of convenience and no vice trauma. Therefore, it is a focal point of research in the present neurological field.In this study, we use anti-Aβantibody to treat AD rats via nasal administration. The purpose of this study is to test the feasibility of anti-Aβantibody treat AD via nasal administration.Methods1. Experimental animals and groups:Male health Wistar rats (n=15) were randomly devided into three groups: control group (n=5), AD model group (n=5) and treatment group (n=5).2. To establish AD models: Rats in AD model group and treatment group were injected condensed Aβinto bilateral hippocampus. Rats in control group were injected saline. Three days later, water maze experiment was practice to test whether AD models are succeed.3. Nasal administration:Three days after establish AD models, anti-Aβantibody was given through nasal cavity. Succesive medicate for seven days. Rats in treatment group and control group were given horse-radish peroxidase-labeled anti-Aβantibody, while rats in AD model group were given saline.4. Water maze experiment:Use water maze experiment to test behavior change of rats. Rats were trained for three days before establish AD models. Water maze experiment was practiced at three and ten days after establish AD models.5. Detect Aβ:Immunohistological assessments were performed to examine Aβ. Examined and photographed using computerized video imaging microscopy. Data were acquired at cortex region by analysing the positive area percentage at high power magnification (400×).6. Statistical analysis:All data were expressed as x|-±s. The results were analyzed using t-test and processed by SPSS 13.0. A value P<0.05 was considered statistically significant.Results1. Water maze experiment:There was no significant difference of water maze results among each groups before establish AD models(P>0.05). Three and ten days later, the escape latency of AD model group and treatment group were significantly longer than that of control group (P<0.05), and the escape latency of AD model group was significantly longer than that of treatment group ten days later(.P<0.05).2. Deposition of Aβin brain:There was no Aβdeposition in control group, and there was a great quantity deposition in AD model group and treatment group. The positive cell in treatment group was significant fewer than that of AD model group(P<0.05).Conclusions1. Anti-Aβantibody given through nasal cavity can bypass BBB and be distributed over cortex, hippocampus and pars thalamica region.2. Anti-Aβantibody can improve recognition defect and decrease Aβdeposition of AD rats.