Dreier J P, Ebert N, Priller J, Megow D, Lindauer U, Klee R, Reuter U, Imai Y, Einhäupl K M, Victorov I, Dirnagl U
Department of Neurology and Physiology, Charité, Humboldt-University, Berlin, Germany.
J Neurosurg. 2000 Oct;93(4):658-66. doi: 10.3171/jns.2000.93.4.0658.
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.
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 Hb 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).
The authors conclude that subarachnoid Hb combined with either a high K+ or a low glucose concentration leads to widespread necrosis of the cortex.
蛛网膜下腔出血后迟发性缺血性神经功能缺损的发病机制与溶血产物有关。先前研究表明，向脑表面灌注含溶血产物钾离子（K⁺）和血红蛋白（Hb）的人工脑脊液（ACSF）可在大鼠中诱发缺血。在缓慢的血管痉挛反应基础上，缺血事件表现为神经胶质网络的扩散性去极化，进而引发急性血管收缩。本研究的目的是探讨皮质中的这种扩散性缺血是否会导致脑损伤。
对31只大鼠植入颅骨视窗。使用激光多普勒血流仪测量脑血流量（CBF），并记录直流（DC）电位。将ACSF局部灌注到脑表面。大鼠被分为五组，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化钙结合衔接分子）以及末端脱氧核苷酸转移酶介导的脱氧尿苷三磷酸缺口末端标记检测。灌注含Hb并结合高浓度K⁺（35 mmol/L，16只动物）或低浓度葡萄糖（0.8 mmol/L，4只动物）的ACSF会使CBF逐渐降低。当CBF降至与基线相比为40%至70%（基线视为100%）时，皮质出现扩散性缺血。这种扩散性缺血的特征是DC出现急剧的负向偏移，随后CBF急剧下降，接着缓慢恢复（平均持续时间60分钟）。在存活的14只动物中，有12只在颅骨视窗部位及邻近区域观察到广泛的皮质梗死，这与三个对照组（11只动物）的结果不同。
作者得出结论，蛛网膜下腔Hb与高K⁺或低葡萄糖浓度相结合会导致皮质广泛坏死。
