颅脑损伤后内源性神经干细胞增殖与迁移中的基质细胞衍生因子1

Role of stromal cell derived factor-1 in proliferation and migration of endogenous neural stem cells after traumatic brain injury

背景:神经干细胞的迁移在颅脑损伤中起着极其重要的作用,但是其具体迁移机制尚不明确。目的:观察大鼠颅脑损伤后基质细胞衍生因子1在内源性神经干细胞的增殖与迁移中的作用。方法:采用Feeney’s等的方法用自制自由落体撞击器撞击大鼠左侧皮质运动感觉区以制备大鼠中度重型颅脑损伤模型,于伤后6h,3d,5d,7d灌注取脑,通过冰冻切片免疫组织化学检测Nestin及基质细胞衍生因子1表达,比较分析大鼠颅脑损伤后基质细胞衍生因子1和内源性神经干细胞的增殖与迁移之间的关系。并设正常对照组和假手术组做对照。结果与结论:颅脑损伤大鼠的神经行为学评分与对照组比较差异显著。冰冻切片免疫组织化学显示:伤后3d,基质细胞衍生因子1表达较对照组明显,海马区可见大量Nestin阳性细胞,未见向损伤区迁移;伤后5d和7d,基质细胞衍生因子1表达更明显,范围扩大,损伤区可见少量Nestin阳性细胞。对照组及假手术组未有上述改变。结果表明大鼠颅脑损伤后基质细胞衍生因子1表达时间推移越加明显,提示基质细胞衍生因子1参与内源性神经干细胞的增殖及向损伤区迁移的过程。

BACKGROUND： The migration of neural stem cells plays an important role in brain injury, but its specific mechanism is still unclear. OBJECTIVE： To observe the role of stromal cell derived factor-1 （SDF-1） in proliferation and migration of endogenous neural stem cells after traumatic brain injury in rats. METHODS： The left motor and sensory cortical areas in rats were hit by self-made free-fall drop using Feeney’s method in order to establish the moderate and severe traumatic brain injury model. The brains were removed at 6 hours, 3, 5 and 7 days after injury. Immunohistochemical analysis of Nestin and SDF-1 was performed on frozen sections. The correlation between proliferation and migration of endogenous neural stem cells and SDF-1 was analyzed. Control group and sham-operated group were taken as control. RESULTS AND CONCLUSION： The difference of neuroethology assessments between the brain injury group and the control group was significant. Immunohistochemical analysis on frozen sections showed： the SDF-1 was increased significantly compared with the control group at 3 days after injury, a great amount of Nestin-positive cells were seen in the hippocampus and none in the injured region. The SDF-1 expression was increased and distributed more obviously and widely at 5 and 7 days, and few Nestin-positive cells were seen in the injured region. There were no changes in the control and sham-operated groups. It is indicated that the expression of SDF-1 is increased as time going on after brain injury, and SDF-1 is involved in the proliferation and migration of endogenous neural stem cells to the injured region.