J Korean Neurol Assoc > Volume 21(2); 2003 > Article

Journal of the Korean Neurological Association 2003;21(2): 183-190.

백서 뇌출혈모델에서의 인간신경줄기세포이식

정상욱 , 주 건 정근화 김승업 김만호 노재규

서울대학교 의과대학 신경과학교실 임상의학연구소,아주대학교 뇌질환 연구소

"Human Neural Stem Cells Transplantation in Experimental Intracerebral Hemorrhage"

Sang-Wuk Jeong

"Department of Neurology and Neural stem cell laboratory, Clinical Research Institute Seoul National University Hospital,Brain Disease Research Center, Ajou University"

Abstract

"Background : Intracerebral hemorrhage (ICH) is associated with a considerable proportion of stroke and head injuries, but except for supportive care, there is no medical therapy available. Transplantation of human neural stem cells (NSCs) can be used to reduce behavioral deficit in experimental ischemic infarct model. However, effect of stem cell transplantation in experimental intracerebral hemorrhage (ICH) is unknown. We hypothesized that NSCs could migrate and differentiate into neurons or glial cells, and improve functional outcome in ICH. Methods : Experimental ICH was made by intrastriatal administration of bacterial collagenase in adult rats. Animals were randomized to receive intravenously either immortalized Lac-Z positive human NSCs (5 ×1 0 6 in 500 μL, n=15) or same volume of saline (n=12) on the following day. Animals were evaluated for 8 weeks after surgery with behavioral test battery. After 8 weeks, animals were sacrificed and the brains were sectioned. Transplanted NSCs were detected by X-gal histochem-istry or β-gal immunohistochemistry, and differentiation of grafted NSCs were evaluated by double labeling of GFAP, NeuN, or neurofilament. Results : Transplanted NSCs migrated to the side of peri-hematomal areas, and differentiated into neurons and astrocytes. NSCs injection group showed improved performances on rotarod test after 2 weeks and on limb placing test after 5 weeks compared with control group (p<0.05) and these effect persisted up to 8 weeks. Conclusions : Intravenously injected NSCs enter rat brain with ICH, and differentiate into astrocytes or neuronal cell, which lead to functional recovery. These findings show the possibility that NSCs can be used to reduce neurological deficits in the experimental ICH.Key Words : Intracerebral hemorrhage, Neural stem cell, Neural transplantation, Immunohistochemistry"