Ninjurin1 Contributes to Blood-Brain Barrier Protection in the Photothrombotic Stroke Model
Photothrombosis 뇌졸중 모델의 뇌혈관장벽 보호에 관여하는 Ninjurin1의 기능에 관한 연구
- 약학대학 약학과
- Issue Date
- 서울대학교 대학원
- 학위논문 (석사)-- 서울대학교 대학원 : 약학과(의약생명과학전공), 2015. 8. 김규원.
- Nerve injury induced protein 1 (Ninjurin1, Ninj1) is a homophilic adhesion molecule that promote neurite extension via cell-cell interaction in the peripheral nervous system. In addition, Ninj1 mediates leukocyte trafficking in experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis. Previous studies were mainly investigated the function of Ninj1 in EAE pathogenesis. However, little is known about Ninj1's function in Central Nervous System(CNS). Therefore, we now studied the role of Ninj1 on another CNS inflammatory disease such as ischemic stroke.
For making the ischemic stroke model, 8-10 weeks C57BL/6 mouse were subjected to ischemia by photothrombosis (PT). Using the custom-made Ninj1 antibody, we first examed the Ninj1 localization in normal and PT mouse brain. In normal brain, Ninj1 was expressed in macrophages of meninges. Interestingly, Ninjurin1 signals were dominantly detected in penumbra area surrounding the lesion core and weakly in endothelial cells in the lesion core after stroke in the early stage. The number of Ninjurin1 positive cells are increased in lesion core region according to stroke progression in the later stage.
To examine the Ninjurin1-expressing cell-types, we double-stained Ninjurin1 with immune cell markers such as CD45 (leukocyte), F4/80 (macrophage). Ninj1 was merged with CD45, F4/80 especially with F4/80. Furthermore, focal brain injury in Ninj1 KO mice led to the Blood-Brain Barrier(BBB) disruption as the lacking of Claudin5 and increased infarct volume in the recovery stage.
Altogether, we clarified that Ninjurin1 has beneficial roles for BBB protection by modulating the BBB intensity and distribution in macrophage of stroke tissue. Thus, our results suggest that Ninjurin1 could be a potent drug candidate for ischemic stroke treatments.