Sørensen J C, Mattsson B, Andreasen A, Johansson B B
Department of Anatomy and Cytology, Institute of Medical Biology, University of Odense, Winslowparken 19, DK-5000, Odense C, Denmark.
Brain Res. 1998 Nov 23;812(1-2):265-9. doi: 10.1016/s0006-8993(98)00943-3.
The study was undertaken to determine if the levels of vesicular zinc in neuronal terminals would decrease in response to focal brain ischemia. The middle cerebral artery was occluded distal to the striatal branches in male spontaneously hypertensive rats. At 7, 15, 30, 45, 60, 90, 120 min; 3, 6, 12, 24, 48 h and 7 days later the animals were sacrificed and the brains were stained for zinc-sulfides, cell bodies and AChE-positive cholinergic fibers. The density of zinc positive terminals significantly decreased in the neocortical ischemic zone 7 min after middle cerebral artery occlusion (MCAO). In the neocortical layers II and III most zinc positive neuronal terminals disappeared at 7 min after MCAO whereas the zinc positive terminals in layers V and VI remained positive at least 2 h. Beginning at 1 h after MCAO and progressing to 24 h a significant decrease in the density of zinc positive terminals was observed in the dorsolateral striatum, and ventrobasal thalamic nucleus, both major projection areas of the sensorimotor cortex. The disappearance of zinc positive neuronal terminals in the ischemic neocortex and related areas, is most likely due to a neuronal release of vesicular zinc in response to hypoxia. The high extracellular concentration of zinc is thought to be both neuroprotective by blocking the NMDA receptor and neurotoxic by activating neuronal influx of Ca2+ through voltage gated calcium channels. It seems evident that the latter effect of zinc is contributing to the neuronal death in focal brain ischemia.
本研究旨在确定神经元终末中的囊泡锌水平是否会因局灶性脑缺血而降低。在雄性自发性高血压大鼠中，大脑中动脉在纹状体分支的远端被阻断。在阻断后7、15、30、45、60、90、120分钟；3、6、12、24、48小时和7天后，处死动物，对大脑进行硫化锌、细胞体和乙酰胆碱酯酶阳性胆碱能纤维染色。大脑中动脉闭塞（MCAO）后7分钟，新皮质缺血区锌阳性终末的密度显著降低。在新皮质的II层和III层，大多数锌阳性神经元终末在MCAO后7分钟消失，而V层和VI层的锌阳性终末至少在2小时内仍为阳性。从MCAO后1小时开始并持续到24小时，在感觉运动皮质的两个主要投射区域背外侧纹状体和腹基底丘脑核中，观察到锌阳性终末的密度显著降低。缺血性新皮质和相关区域中锌阳性神经元终末的消失，很可能是由于神经元对缺氧反应而释放囊泡锌所致。锌的细胞外高浓度被认为既通过阻断NMDA受体具有神经保护作用，又通过电压门控钙通道激活神经元钙内流而具有神经毒性作用。锌的后一种作用似乎促成了局灶性脑缺血中的神经元死亡。
