Neurogenesis and neuronal commitment following ischemia in a new mouse model for neonatal stroke
Neurogenesis and neuronal commitment following ischemia in a new mouse model for neonatal stroke
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DOI：
10.1016/j.brainres.2008.02.037
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发表时间：
2008-05-07
期刊：
影响因子：
2.9
通讯作者：
Comi, A. M.
中科院分区：
文献类型：
--
作者：
Kadam, S. D.;Mulholland, J. D.;Comi, A. M.
新生儿脑卒中是神经系统疾病的重要原因。为了表征新生儿脑缺血后存活延迟后神经前体细胞增殖和成熟的动力学，我们仅使用单侧颈动脉结扎在出生后12天的CD 1小鼠中产生梗死。我们研究了损伤后齿状回脑室下区和颗粒下区的神经发生。在损伤后1周（P18-20），通过5次腹腔注射（每次50 mg/kg）用溴脱氧尿苷标记新产生的细胞。随后的迁移和分化的新生细胞进行了研究，在出生后第40天的分子神经元和神经胶质细胞谱系标记和BrdU掺入的免疫组化。甲酚紫染色显示同侧隔海马CA 3和CA 1区神经元大量丢失，伴有萎缩。无论是损伤侧还是对侧未损伤侧海马，新生细胞总数均显著降低，并与损伤引起的萎缩相关。然而，在齿状回的双边百分比神经元的承诺，没有显着不同的控制。新生儿中风后新皮质和纹状体的新细胞密度双侧增加。SVZ衍生的新细胞的主要非神经元定型与对照中非神经元定型的百分比相似。总之，在模型中新生儿缺血后1周发生的神经发生维持了与假手术对照相似的细胞谱系定型模式。然而，海马SGZ衍生的新神经元的总数减少双边相比，SVZ衍生的神经发生被放大。(C)2008 Elsevier B. V.保留所有权利。
Stroke in the neonatal brain is an important cause of neurologic morbidity. To characterize the dynamics of neural progenitor cell proliferation and maturation after survival delays in the neonatal brain following ischemia, we utilized unilateral carotid ligation alone to produce infarcts in postnatal day 12 CD1 mice. We investigated the neurogenesis derived from the sub-ventricular zone and the sub-granular zone of the dentate gyrus subsequent to injury. Newly produced cells were labeled by bromodeoxyuridine at similar to 1 week (P18-20) after the insult by 5 I.P. injections (each 50 mg/kg). Subsequent migration and differentiation of the newborn cells was investigated at postnatal day 40 by immunohistochemistry for molecular neuronal and glial cell-lineage markers and BrdU incorporation. Cresyl violet stain demonstrated massive loss of neurons in the ipsilateral septal hippocampus in the CA3 and CA1 regions associated with atrophy. Total counts of new cells were significantly lowered not only in the ipsilateral injured but also the contralateral uninjured hippocampi and correlated with the lesion induced atrophy. Bilateral percent neuronal commitments in the dentate gyri however, were not significantly different from control. New cell densities in the neocortex and striatum increased bilaterally after neonatal stroke. The predominantly non-neuronal commitment of the SVZ-derived new cells was similar to the percentage of non-neuronal commitment in controls. In conclusion, neurogenesis occurring at 1 week after neonatal ischemia in the model maintained cell-lineage commitment patterns similar to sham controls. However, the total number of hippocampal SGZ-derived new neurons was reduced bilaterally; in contrast, the SVZ-derived neurogenesis was amplified. (C) 2008 Elsevier B.V. All rights reserved.