Back Stephen A, Craig Andrew, Kayton Robert J, Luo Ning Ling, Meshul Charles K, Allcock Natalie, Fern Robert
Department of Pediatrics, Oregon Health and Sciences University, Portland, Oregon, USA.
J Cereb Blood Flow Metab. 2007 Feb;27(2):334-47. doi: 10.1038/sj.jcbfm.9600344. Epub 2006 Jun 7.
Ischemia is implicated in periventricular white matter injury (PWMI), a lesion associated with cerebral palsy. PWMI features selective damage to early cells of the oligodendrocyte lineage, a phenomenon associated with glutamate receptor activation. We have investigated the distribution of glutamate in rat periventricular white matter at post-natal day 7. Immuno-electron microcopy was used to identify O4(+) oligodendroglia in control rats, and a similar approach was employed to stain glutamate in these cells before and after 90 mins of hypoxia-ischemia. This relatively brief period of hypoxia-ischemia produced mild cell injury, corresponding to the early stages of PWMI. Glutamate-like reactivity was higher in oligodendrocytes than in other cell types (2.13+/-0.25 counts/microm(2)), and declined significantly during hypoxia-ischemia (0.93+/-0.15 counts/microm(2): P<0.001). Astrocytes had lower glutamate levels (0.7+/-0.07 counts/microm(2)), and showed a relatively small decline during hypoxia-ischemia. Axonal regions contained high levels of glutamate (1.84+/-0.20 counts/microm(2)), much of which was lost during hypoxia-ischemia (0.72+/-0.20 counts/microm(2): P>0.001). These findings suggest that oligodendroglia and axons are the major source of extracellular glutamate in developing white matter during hypoxia-ischemia, and that astrocytes fail to accumulate the glutamate lost from these sources. We also examined glutamate levels in the choroid plexus. Control glutamate levels were high in both choroid epithelial (1.90+/-0.20 counts/microm(2)), and ependymal cells (2.20+/-0.28 counts/microm(2)), and hypoxia-ischemia produced a large fall in ependymal glutamate (0.97+/-0.08 counts/microm(2): P>0.001). The ependymal cells were damaged by the insult and represent a further potential source of glutamate during ischemia.
缺血与脑室周围白质损伤（PWMI）有关，PWMI是一种与脑瘫相关的病变。PWMI的特征是少突胶质细胞谱系早期细胞的选择性损伤，这一现象与谷氨酸受体激活有关。我们研究了出生后第7天大鼠脑室周围白质中谷氨酸的分布。免疫电子显微镜用于识别对照大鼠中的O4(+)少突胶质细胞，在缺氧缺血90分钟前后，采用类似方法对这些细胞中的谷氨酸进行染色。这段相对短暂的缺氧缺血导致了轻度细胞损伤，与PWMI的早期阶段相对应。少突胶质细胞中谷氨酸样反应性高于其他细胞类型（2.13±0.25计数/μm²），在缺氧缺血期间显著下降（0.93±0.15计数/μm²：P<0.001）。星形胶质细胞的谷氨酸水平较低（0.7±0.07计数/μm²），在缺氧缺血期间下降相对较小。轴突区域含有高水平的谷氨酸（1.84±0.20计数/μm²），其中大部分在缺氧缺血期间丢失（0.72±0.20计数/μm²：P>0.001）。这些发现表明，少突胶质细胞和轴突是缺氧缺血期间发育中的白质细胞外谷氨酸的主要来源，并且星形胶质细胞无法积累从这些来源丢失的谷氨酸。我们还检测了脉络丛中的谷氨酸水平。对照时脉络丛上皮细胞（1.90±0.20计数/μm²）和室管膜细胞（2.20±0.28计数/μm²）中的谷氨酸水平都很高，缺氧缺血导致室管膜谷氨酸大幅下降（0.97±0.08计数/μm²：P>0.001）。室管膜细胞因损伤而受损，是缺血期间谷氨酸的另一个潜在来源。
