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Cell Treatment for Stroke in Type Two Diabetic Rats Improves Vascular Permeability Measured by MRI

机译:对2型糖尿病大鼠中风的细胞治疗可改善MRI测量的血管通透性

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摘要

Treatment of stroke with bone marrow stromal cells (BMSC) significantly enhances brain remodeling and improves neurological function in non-diabetic stroke rats. Diabetes is a major risk factor for stroke and induces neurovascular changes which may impact stroke therapy. Thus, it is necessary to test our hypothesis that the treatment of stroke with BMSC has therapeutic efficacy in the most common form of diabetes, type 2 diabetes mellitus (T2DM). T2DM was induced in adult male Wistar rats by administration of a high fat diet in combination with a single intraperitoneal injection (35mg/kg) of streptozotocin. These rats were then subjected to 2h of middle cerebral artery occlusion (MCAo). T2DM rats received BMSC (5x106, n = 8) or an equal volume of phosphate-buffered saline (PBS) (n = 8) via tail-vein injection at 3 days after MCAo. MRI was performed one day and then weekly for 5 weeks post MCAo for all rats. Compared with vehicle treated control T2DM rats, BMSC treatment of stroke in T2DM rats significantly (p<0.05) decreased blood-brain barrier disruption starting at 1 week post stroke measured using contrast enhanced T1-weighted imaging with gadopentetate, and reduced cerebral hemorrhagic spots starting at 3 weeks post stroke measured using susceptibility weighted imaging, although BMSC treatment did not reduce the ischemic lesion volumes as demarcated by T2 maps. These MRI measurements were consistent with histological data. Thus, BMSC treatment of stroke in T2DM rats initiated at 3 days after stroke significantly reduced ischemic vascular damage, although BMSC treatment did not change infarction volume in T2DM rats, measured by MRI.
机译:在非糖尿病性中风大鼠中,骨髓基质细胞(BMSC)治疗中风可显着增强大脑重塑并改善神经功能。糖尿病是中风的主要危险因素,并诱发可能影响中风治疗的神经血管变化。因此,有必要检验我们的假设,即以BMSC治疗中风对糖尿病的最常见形式即2型糖尿病(T2DM)具有治疗功效。通过给予高脂饮食和单次腹膜内注射(35mg / kg)链脲佐菌素,在成年雄性Wistar大鼠中诱发T2DM。然后对这些大鼠进行2h的大脑中动脉闭塞(MCAo)。 T2DM大鼠在MCAo后3天通过尾静脉注射接受了BMSC(5x10 6 ,n = 8)或等体积的磷酸盐缓冲盐水(PBS)(n = 8)。所有大鼠在MCAo后一天进行MRI,然后每周进行一次,持续5周。与用媒剂治疗的对照T2DM大鼠相比,BMSC治疗T2DM大鼠中风显着(p <0.05)减少了卒中后1周开始的血脑屏障破坏,这是通过使用对比增强的ado多戊酸酯T1加权成像测量的,并减少了脑出血点的开始尽管BMSC治疗并未减少T2图所划定的缺血性病变体积,但仍使用药敏加权成像在卒中后3周进行了观察。这些MRI测量结果与组织学数据一致。因此,尽管通过MRI测量,BMSC治疗并没有改变T2DM大鼠的梗死体积,但是BMSC治疗在中风后3天开始的T2DM大鼠中风显着减少了缺血性血管损伤。

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