Axon conduction and survival in CNS white matter during energy deprivation: A developmental study

Axon conduction and survival in CNS white matter during energy deprivation: A developmental study
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DOI:
10.1152/jn.1998.79.1.95
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发表时间:
1998-01-01
影响因子:
2.5
通讯作者:
Ransom, BR
Ransom, BR
中科院分区:
医学3区
文献类型:
--
作者:
Fern, R;Davis, P;Ransom, BR

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我们研究了出生后发育的轴突敏感性的撤回氧气,葡萄糖,或联合撤回氧气+葡萄糖在离体大鼠视神经(中枢神经系统白色物质道)。通过诱发复合动作电位(CAP)的丧失来评估,去除氧气或葡萄糖60分钟导致成年大鼠视神经的不可逆损伤。视神经在年龄45分钟造成选择性损失的晚期CAP组件,这是没有看到缺氧。早期成分的振幅恢复到94.8%的控制后60分钟的葡萄糖戒断,虽然总CAP面积恢复到只有42.3%。联合氧+葡萄糖撤退60分钟产生了更大程度的永久CAP损失比60分钟的葡萄糖或氧撤退单独在视神经从大鼠年龄大于P4。年轻于P4的视神经在60分钟的联合氧+葡萄糖戒断中没有表现出永久性功能丧失。出乎意料的是,来自P21-P49大鼠的视神经在所有三种条件后恢复显著低于成年视神经(>P50)。很可能,这一最后髓鞘形成时期对应于白色物质代谢活动增强的时期。中枢神经系统白色物质对能量剥夺的耐受性可分为4个阶段,并与其发育特征相关:髓鞘形成前期(P0-P4),对缺氧、缺糖和缺氧/缺糖联合耐受性强;髓鞘形成晚期(P21-P49),对缺氧、血糖缺乏和缺氧/血糖缺乏的耐受性非常低;和成熟(>P50),对缺氧、血糖缺乏和缺氧/血糖缺乏的耐受性低。与无氧条件下葡萄糖戒断相比,视神经功能在氧存在下对葡萄糖戒断的相对阻力可能是由于存在氧依赖性能量储备,如星形胶质细胞糖原、氨基酸和磷脂。
We investigated the postnatal development of axon sensitivity to the withdrawal of oxygen, glucose, or the combined withdrawal of oxygen + glucose in the isolated rat optic nerve (a CNS white matter tract). Removal of either oxygen or glucose for 60 min resulted in irreversible injury in optic nerves from adult rats, assessed by loss of the evoked compound action potential( CAP). Optic nerves at ages 45 min caused the selective loss of late CAP components; this was not seen with oxygen deprivation. The amplitude of the early component recovered to 94.8% of control after 60 min of glucose withdrawal, although total CAP area recovered to only 42.3%. Combined oxygen + glucose withdrawal for 60 min produced a greater degree of permanent CAP loss than 60 min of glucose or oxygen withdrawal individually in optic nerves from rats older than P4. Younger than P4 optic nerves showed no permanent loss of function from 60 min of combined oxygen + glucose withdrawal. Unexpectedly, optic nerves from P21-P49 rats recovered significantly less after all three conditions than adult optic nerves (>P50). It is probable that this period of final myelination corresponds to a time of heightened metabolic activity in white matter. The tolerance of CNS white matter to energy deprivation can be categorized into four stages that are correlated with specific developmental features: premyelination (P0-P4), highly tolerant to anoxia, aglycemia and combined anoxia/aglycemia; early myelination (P5-P20), partially tolerant of anoxia and aglycemia but not to combined anoxia/aglycemia; late myelination (P21-P49), very low tolerance of anoxia, aglycemia and combined anoxia/aglycemia; and mature (>P50), low tolerance of anoxia, aglycemia and combined anoxia/aglycemia. The relative resistance of optic nerve function to glucose withdrawal in the presence of oxygen, compared with glucose withdrawal in the absence of oxygen, is presumably due to the presence of oxygen-dependent energy reserves such as astrocytic glycogen, amino acids and phospholipids.