Effect of apolipoprotein E genetic polymorphism in repair of blood brain barrier breakdown following traumatic brain injury / 中华创伤杂志

ABSTRACT

Objective To investigate the effect and underlying mechanism of apolipoprotein E (APOE) genetic polymorphism in treating blood brain barrier (BBB) breakdown after traumatic brain injury (TBI).Methods Human APOE knock-in mice (ε3,ε4),APOE knockout mice,and APOE wild-type mice with each numbering 80 were respectively divided into TBI group (n =50),sham-operation group (n =15) and normal control group (n =15) according to the random number table.TBI group was subdivided at 1 day (n=15),3 days (n=15),and7 days (n=20).TBI was induced with a pneumatically operated injury device.BBB permeability to large or small molecules was evaluated by measuring Evans blue (EB) and fluorescein sodium (NaFI) extravasation into the damage area at 1,3,and 7 days postinjury.Brain water content was determined using the dry-wet method.Western blotting and qRT-PCR for tight junction-associated proteins Occludin and Claudin-5 were performed at 7 days postinjury.Results With respect to normal control group,BBB permeability to EB and NaFI was significantly higher in ε4 and APOE knockout mice than in ε3 and APOE wild-type mice.There appeared significant increase in BBB permeability to EB and NaFI in TBI group,with insignificant differences among rats of each genotype at 1 and 3 days postinjury (P ＞ 0.05).Whereas at 7 days postinjury,BBB permeability to EB in APOE wild-type and e3 mice returned to the normal level (P ＞ 0.05),but it re mained at a high level in APOE knockout and ε4 mice (P ＜ 0.01).Meanwhile,BBB permeability toNaFI was significantly higher in ε4 and APOE knockout mice than in ε3 and APOE wild-type mice (P ＜ 0.01).Brain water content was equivalent among rats of each genotype at 1,3 and 7 days postinjury (P ＞0.05).Western blotting and qRT-PCR demonstrated Occludin and Claudin-5 in ε4 and APOE knockout mice were significantly lower than those in ε3 and APOE wide-type mice (P ＜ 0.05).Conclusion APOE plays an important role in restoration of BBB function after TBI,but ε4 may impede the recovery of BBB breakdown after TBI through its effect on tight junction.