Calcium Ion Transients in Peri-Infarct Depolarizations May Deteriorate Ion Homeostasis and Expand Infarction in Focal Cerebral Ischemia in Cats
Calcium Ion Transients in Peri-Infarct Depolarizations May Deteriorate Ion Homeostasis and Expand Infarction in Focal Cerebral Ischemia in Cats
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DOI：
10.1161/01.str.32.2.535
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发表时间：
2001-02
期刊：
影响因子：
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通讯作者：
K. Ohta;R. Graf;G. Rosner;W. Heiss
中科院分区：
文献类型：
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作者：
K. Ohta;R. Graf;G. Rosner;W. Heiss
背景和目的——梗死周围去极化（PIDs）的有害影响可能依赖于复发性Ca2+内流。到目前为止，很少有研究证明PIDs与脑回畸形动物的相关性，并且该过程的进行性尚未在较长时间内进行研究。因此，我们研究了猫长期局灶性缺血时细胞外钙（[Ca2+]o）的时空变化与直流电（DC）电位、一氧化氮（NO）浓度和局部脑血流量变化的关系，以及最终的病理结果。方法-在氟烷麻醉的猫中，接受载药（n=12）或MK-801 (5 mg/kg IV; n=10)，永久闭塞左大脑中动脉。激光多普勒探针、离子选择微电极和NO电极同时测量左脑皮层外脑回和上脑回的脑血流、直流电位、皮质电图、[Ca2+]o和NO浓度。结果：药组动物大脑中动脉闭塞后出现10个外脑回和4个后脑回的持续去极化，mk -801组动物出现9个后脑回和3个后脑回的持续去极化。仅在4只药后动物的上脑回中检测到与[Ca2+]o短暂性降低相关的PIDs，其中3只发生复发性PIDs。在PIDs期间，皮质电图被抑制，皮质电图恢复随着连续去极化而逐步恶化。随着缺血的持续，PID持续时间略有增加，并在最后阶段演变为持续去极化。PID期间未检测到NO瞬态，局部脑血流瞬态不明显。初始持续去极化组的梗死比PID组大，mk -801组的梗死最小。结论：在猫的梗死周围区，PID并不常见，它可以被n -甲基-d-天冬氨酸拮抗剂MK-801抑制。然而，如果产生重复的PIDs，它们会导致神经元功能和离子稳态的逐步进行性破坏，可能导致局灶性脑缺血梗死的增长。反复的Ca2+内流可能是促成这一过程的一种机制。
Background and Purpose — Harmful effects of peri-infarct depolarizations (PIDs) may depend on recurrent Ca2+ influx. Thus far, few studies have documented the relevance of PIDs in gyrencephalic animals, and the progressive nature of this process has not been investigated over extended periods. We therefore studied in prolonged focal ischemia in cats spatial and temporal profiles of extracellular calcium ([Ca2+]o) shifts in relation to direct current (DC) potential, nitric oxide (NO) concentration and regional cerebral blood flow alterations, and final pathological outcome. Methods — In halothane-anesthetized cats receiving either vehicle (n=12) or MK-801 treatment (5 mg/kg IV; n=10), the left middle cerebral artery was permanently occluded. Laser-Doppler probes, ion-selective microelectrodes, and NO electrodes measured simultaneously regional cerebral blood flow, DC potential, electrocorticogram, [Ca2+]o, and NO concentrations in ectosylvian and suprasylvian gyri of the left cerebral cortex. Results — Persistent depolarization immediately after middle cerebral artery occlusion occurred in 10 ectosylvian and 4 suprasylvian gyri of vehicle-treated animals and in 9 ectosylvian and 3 suprasylvian gyri of MK-801–treated animals. PIDs associated with transient decreases of [Ca2+]o were detected in suprasylvian gyri of only 4 vehicle-treated animals, of which 3 developed recurrent PIDs. Electrocorticogram was suppressed during PIDs, and electrocorticogram recovery worsened in a stepwise manner with consecutive depolarizations. PID duration increased slightly with ongoing ischemia and evolved to persistent depolarization at a final stage. NO transients were not detected during PID, and regional cerebral blood flow transients were not pronounced. Infarction was larger with initial persistent depolarization than with PID and was smallest in MK-801–treated animals. Conclusions — PID is not a common finding in peri-infarct zones in cats, and it is suppressed by the N-methyl-d-aspartate antagonist MK-801. However, if repeated PIDs are generated, they result in a stepwise, progressive breakdown of neuronal function and ion homeostasis, probably contributing to the growth of infarction in focal cerebral ischemia. Recurrent Ca2+ influx is a mechanism that presumably contributes to this process.