Intracerebral transplantation of bone marrow stromal cells improves motor behavior at different period of cerebral ischemic rats

• Main Authors: Lo Yo Chih, 羅友志
• Other Authors: 王順德
• Format: Others
• Language: zh-TW
• Published: 2009
• Online Access: http://ndltd.ncl.edu.tw/handle/71924493066662609594

碩士 === 國防醫學院 === 生物及解剖學研究所 === 97 === Cerebrovascular diseases have been in the top of the ten leading causes of death in Taiwan. The ischemic stroke is the most common type among theses diseases. The thrombolytic therapy is the current clinical procedure using to treat acute ischemic stroke. However, when thrombolytic therapy is not work, it would cause permanent brain damage. Recent year studies suggest that stem cells transplantation may provide the alternate way to improve the efficacy of ischemic stroke treatment. When adult bone marrow non-hematopoietic stromal cells (BMSCs) were placed into different microenvironment, these cells would be induced to differentiate into osteoblast, chondrocyte, myocyte, adipocyte, and neuron. Recent studies revealed that BMSCs transplantation could improve neurological deficits of various damages or central nervous system (CNS) disease such as Parkinson’s disease and stroke. However, these studies have not examined the optimal transplant time yet. To find out the best treatment opportunity, the present study transplants BMSCs followed at different stroke time. The middle cerebral artery occlusion (MCAo) as an infarct animal model to be made and was performed behavior test day after injury. BMSCs were transplanted into the striatum at bregma, 3 mm lateral to midline and 4 mm vertical to dura at 1 day, 7 days and 14 days after MCAo. Rats were performed the modified neurological severity scores (mNSS) behavior test following 14 days after BMSCs transplant and sacrificed at the last day. To use 2.3.5-Triphenylterazolium hydrochloride (TTC) stain, anti-human nuclei and anti-GFAP immunohistochemistry (IHC) stain to examine the infarction area, the survival and migration of BMSCc and the gliosis. The mNSS scores are 4.30±0.52, 4.20±0.41 and 4.67±0.52 followed 1 day, 7 days and 14 days after BMSCs transplantation respectively. The infarction areas are 3.57±0.86, 3.87±0.70, 3.77±0.59 in 15 days, 21 days, and 28 days after MCAo and 2.61±0.79%, 2.62±0.92% and 3.23±0.79% in 1 day, 7 days, and 14 days group compared to the non-infarction side. The results show that both the motor behavior and infarction areas have significant improvement and attenuation (p< 0.05) at 1 day and 7 days but not 14 days after transplant. Also, immunohistochemical staining results demonstrate that the BMSCs survive and migrate to the infarction area after 14 days transplantation. The thickness of scar are 337.9±47.9, 116.7±32.6, 131.6±28.3 and 196.0±86.8μm in untreated, 1 day, 7 days, and 14 days group. There is less gliosis in the treated groups. These results may suggest that the optimal timing for BMSCs transplantation would be taken place within one week after ischemic stroke. Also, the BMSCs may contribute to the motor behavioral improvement, gliosis inhibition and decrease infarction area, but the mechanisms need to be further investigation.