Products of hemolysis in the subarachnoid space inducing spreading ischemia in the cortex and focal necrosis in rats: a model for delayed ischemic neurological deficits after subarachnoid hemorrhage?
Products of hemolysis in the subarachnoid space inducing spreading ischemia in the cortex and focal necrosis in rats: a model for delayed ischemic neurological deficits after subarachnoid hemorrhage?
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DOI：
10.3171/jns.2000.93.4.0658
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发表时间：
2000-10-01
影响因子：
4.1
通讯作者：
Dirnagl, U
中科院分区：
文献类型：
--
作者：
Dreier, JP;Ebert, N;Dirnagl, U
物体。蛛网膜下腔出血后迟发性缺血性神经功能障碍的发病机制与溶血产物有关。含有溶血产物K+和血红蛋白(Hb)的人工脑脊液(ACSF)局部脑灌流可诱导大鼠脑缺血。叠加在缓慢的血管痉挛反应上，缺血事件代表了神经元-神经胶质网络的扩散性去极化，引发了急性血管收缩。本研究的目的是探讨大脑皮层弥漫性脑缺血是否导致脑损伤。31只大鼠植入颅窗。用激光多普勒血流仪测定脑血流量(CBF)，并记录直流电。ACSF在大脑上局部超融合。大鼠被分成五组，代表不同的ACSF成分。分析包括经典的组织化学和免疫组织化学研究(胶质纤维酸性蛋白和离子钙结合接头分子)以及末端脱氧核苷酸转移酶介导的脱氧尿嘧啶核苷缺口末端标记分析。含KB的ACSF联合高浓度K+(35 mmoL/L，16只动物)或低浓度葡萄糖(0.8 mmoL/L，4只动物)灌流逐渐减少脑血流量。当脑血流量达到基线(被认为是100%)的40%~70%时，大脑皮质出现广泛性缺血。弥漫性脑缺血的特点是DC急剧负移，随后CBF急剧下降，随后缓慢恢复(平均持续60分钟)。在存活的14只动物中，有12只在颅窗及其邻近区域观察到广泛的皮质梗塞，与三个对照组(11只动物)的发现形成对比。作者的结论是，蛛网膜下腔Hb与高K+或低葡萄糖浓度相结合会导致广泛的皮质坏死。
Object. The pathogenesis of delayed ischemic neurological deficits after subarachnoid hemorrhage has been related to products of hemolysis. Topical brain superfusion of artificial cerebrospinal fluid (ACSF) containing the hemolysis products K+ and hemoglobin (Hb) was previously shown to induce ischemia in rats. Superimposed on a slow vasospastic reaction, the ischemic events represent spreading depolarizations of the neuronal-glial network that trigger acute vasoconstriction. The purpose of the present study was to investigate whether such spreading ischemias in the cortex lead to brain damage.Methods. A cranial window was implanted in 31 rats. Cerebral blood flow (CBF) was measured using laser Doppler flowmetry, and direct current (DC) potentials were recorded. The ACSF was superfused topically over the brain. Rats were assigned to five groups representing different ACSF compositions. Analyses included classic histochemical and immunohistochemical studies (glial fibrillary acidic protein and ionized calcium binding adaptor molecule) as well as a terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling assay.Superfusion of ACSF containing Kb combined with either a high concentration of K+ (35 mmol/L, 16 animals) or a low concentration of glucose (0.8 mmol/L, four animals) reduced CBF gradually. Spreading ischemia in the cortex appeared when CBF reached 40 to 70% compared with baseline (which was deemed 100%). This spreading ischemia was characterized by a sharp negative shift in DC, which preceded a steep CBF decrease that was followed by a slow recovery (average duration 60 minutes). in 12 of the surviving 14 animals widespread cortical infarction was observed at the site of the cranial window and neighboring areas in contrast to findings in the three control groups (11 animals).Conclusions. The authors conclude that subarachnoid Hb combined with either a high K+ or a low glucose concentration leads to widespread necrosis of the cortex.