Glutamate‐Mediated Injury in Focal Cerebral Ischemia: The Excitotoxin Hypothesis Revised
Glutamate‐Mediated Injury in Focal Cerebral Ischemia: The Excitotoxin Hypothesis Revised
复制标题
谷氨酸介导的局灶性脑缺血损伤：兴奋毒素假说的修订
作者：
K. Hossmann
局灶性脑缺血后的神经元损伤被广泛归因于谷氨酸的兴奋毒性作用。然而，对已发表的谷氨酸体外毒性数据进行批判性分析，并将这些数据与体内谷氨酸释放和谷氨酸拮抗剂的治疗效果进行比较，提出了对神经毒性机制的怀疑。谷氨酸介导的损伤的另一种解释是梗塞周围弥漫性抑郁样去极化所致的低氧。这些去极化在缺血区的核心被触发，并以不规则的间隔扩散到梗塞区周围。在缺血未受损的组织中，与弥漫性抑郁相关的代谢工作负荷与血流和氧气供应的增加相结合，确保了氧化呼吸的维持。在局灶性缺血的半影区，侧支循环的血流动力学约束占优势，氧气输送的适当调整，导致相对组织缺氧的一过性发作。低氧会导致蛋白质合成受到抑制，能量代谢逐渐恶化，并导致不可逆转的受损组织进入半影区。
Neuronal injury following focal cerebral ischemia is widely attributed to the excitotoxic effects of gluta‐mate. However, critical analysis of published data on glutamate toxicity in vitro and the comparison of these data with in vivo release of glutamate and the therapeutic effect of glutamate antagonists raises doubts about a neurtoxic mechamism. An alternative explanation for glutamate‐mediated injury is hypoxia due to peri‐infarct spreading depression‐like depolarizations. These depolarizations are triggered in the core of the ischemic infarct and spread at irregular intervals into the peri‐infarct surrounding. In ischemically uncompromised tissue, the metabolic workload associated with spreading depression is coupled to an increase in blood flow and oxygen supply, assuring maintenance of oxidative respiration. In the penumbra region of focal ischemia, the hemodynamic constraints of collateral blood circulation prevail the adequate adjustment of oxygen delivery, leading to transient episodes of relative tissue hypoxia. The hypoxic episodes cause a suppression of protein synthesis, a gradual deterioration of energy metabolism and a progression of irreversibly damaged tissue into the penumbra zone.
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DOI：
10.1002/neu.480230915
发表时间：
1992-11-01
期刊：
JOURNAL OF NEUROBIOLOGY
影响因子：
--
作者：
CHOI, DW
通讯作者：
CHOI, DW
DOI：
--
发表时间：
1987-11
期刊：
The Journal of pharmacology and experimental therapeutics
影响因子：
--
作者：
M. Goldberg;J. Weiss;P. Pham;D. Choi
通讯作者：
M. Goldberg;J. Weiss;P. Pham;D. Choi
影响因子：
56.9
作者：
KAKU, DA;GIFFARD, RG;CHOI, DW
通讯作者：
CHOI, DW
MK-801 对局灶性脑缺血大鼠脑局部耗氧量的影响。
影响因子：
20.1
作者：
Chi,OZ;Anwar,M;Sinha,AK;Weiss,HR
通讯作者：
Weiss,HR
影响因子：
8.3
作者：
KAPLAN, B;BRINT, S;PULSINELLI, W
通讯作者：
PULSINELLI, W