Jackowski A, Crockard A, Burnstock G, Russell R R, Kristek F
Cerebral Oedema Research Group, Institute of Neurology, Queen Square, London, England.
J Cereb Blood Flow Metab. 1990 Nov;10(6):835-49. doi: 10.1038/jcbfm.1990.140.
The rat subarachnoid haemorrhage (SAH) model was further studied to establish the precise time course of the globally reduced CBF that follows and to ascertain whether temporally related changes in cerebral perfusion pressure (CPP) and intracranial pressure (ICP) take place. Parallel ultrastructural studies were performed upon cerebral arteries and their adjacent perivascular subarachnoid spaces. SAH was induced by a single intracisternal injection of autologous arterial blood. Serial measurements of regional cortical CBF by hydrogen clearance revealed that experimental SAH resulted in an immediate 50% global reduction in cortical flows that persisted for up to 3 h post SAH. At 24 h, flows were still significantly reduced at 85% of control values (p less than 0.05), but by 48 h had regained normal values and were maintained up to 5 days post SAH. ICP rose acutely after haemorrhage to nearly 50 mm Hg with C-type pressure waves being present. ICP then fell slowly, only fully returning to control levels at 72 h. Acute hydrocephalus was observed on autopsy examination of SAH animals but not in controls. Reductions in CPP occurred post SAH, but only in the order of 15%, which could not alone account for the fall in CBF that took place. At 48 and, to a lesser extent, 24 h post SAH, myonecrosis confined largely to smooth muscle cells of the immediately subintimal media was observed. No significant changes in the intima or perivascular nerve plexus were seen. Within 24 h of haemorrhage, a limited degree of phagocytosis of erythrocytes by pial lining cells took place. However, early on the second day post SAH, a dramatic increase in the numbers of subarachnoid macrophages arose from a transformation of cells of the pia-arachnoid. This period was characterised by intense phagocytic activity, erythrocytes, fibrin, and other debris being largely cleared over the next 24 h. At 5 days post SAH the subarachnoid macrophage population declined, cells losing their mobile active features to assume a more typical pia-arachnoid cell appearance once more. Our studies indicate that this increasingly utilised small animal model of SAH develops global cortical flow changes only acutely, and it is likely that early vasospasm, secondary to released blood products rather than pressure changes per se, is responsible for the initial cerebral ischaemia that develops. Interestingly, both cerebral arterial vasculopathy and perivascular macrophage phagocytic activity are most marked at approximately 48 h following SAH in the rat, a time at which a phase of delayed cerebral arterial narrowing has previously been documented.
进一步研究大鼠蛛网膜下腔出血（SAH）模型，以确定随后出现的全脑脑血流量（CBF）降低的精确时间进程，并确定脑灌注压（CPP）和颅内压（ICP）是否发生与时间相关的变化。对脑动脉及其相邻的血管周围蛛网膜下腔进行了平行的超微结构研究。通过单次脑池内注射自体动脉血诱导SAH。通过氢清除法对局部皮质CBF进行系列测量，结果显示实验性SAH导致皮质血流立即整体降低50%，并在SAH后持续长达3小时。在24小时时，血流量仍显著降低，为对照值的85%（p<0.05），但到48小时时已恢复正常，并在SAH后维持至5天。出血后ICP急剧上升至近50mmHg，并出现C型压力波。然后ICP缓慢下降，仅在72小时时完全恢复到对照水平。在对SAH动物进行尸检时观察到急性脑积水，但在对照组中未观察到。SAH后CPP降低，但仅降低约15%，这本身不足以解释所发生的CBF下降。在SAH后48小时以及在较小程度上24小时时，观察到肌坏死主要局限于紧邻内膜下中膜的平滑肌细胞。在内膜或血管周围神经丛中未见明显变化。出血后24小时内，软脑膜衬里细胞对红细胞进行了有限程度的吞噬作用。然而，在SAH后第二天早期，蛛网膜下腔巨噬细胞数量急剧增加，这是由软脑膜-蛛网膜细胞转化而来的。这一时期的特点是吞噬活动强烈，在接下来的24小时内红细胞、纤维蛋白和其他碎片基本被清除。在SAH后5天，蛛网膜下腔巨噬细胞数量减少，细胞失去其移动活跃的特征，再次呈现出更典型的软脑膜-蛛网膜细胞外观。我们的研究表明，这种越来越常用的SAH小动物模型仅在急性期出现全脑皮质血流变化，并且很可能是继发于释放的血液产物而非压力变化本身的早期血管痉挛导致了最初发生的脑缺血。有趣的是，大鼠SAH后约48小时，脑动脉血管病变和血管周围巨噬细胞吞噬活动最为明显，此前已有文献记载这一时期存在延迟性脑动脉狭窄阶段。
