Postischemic reperfusion: Ultrastructural blood-brain barrier and hemodynamic correlative changes in an awake model of transient forebrain ischemia
Postischemic reperfusion: Ultrastructural blood-brain barrier and hemodynamic correlative changes in an awake model of transient forebrain ischemia
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DOI：
10.1227/01.neu.0000154702.23664.3d
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发表时间：
2005-03-01
期刊：
影响因子：
4.8
通讯作者：
Diaz, FG
中科院分区：
文献类型：
--
作者：
Melgar, MA;Rafols, J;Diaz, FG
目的：在脑缺血的不可恢复模型中，血脑屏障(BBB)和脑血流量(CBF)在再灌流过程中发生改变。然而，尚不清楚这些CBF和BBB变化是否发生在短暂、短暂的脑缺血和神经恢复之后。本研究的目的是在一个清醒的、恢复的短暂性前脑缺血(GFI)模型中观察脑血流量和血脑屏障超微结构变化的时程。方法：45只成年SD大鼠在清醒状态下，用九支结扎法造成GFI 10min。年龄匹配的35只动物组成假手术组。取正常对照组(n=5)、假手术组(n=5)、九支血管阻断/再灌注组(n=15)进行超微结构观察。脑缺血再灌流24小时后进行脑电检查，并测量脑血流量、平均动脉压和颅内压。用透射电子显微镜对脑缺血再灌注过程中脑血流量发生变化的时间点的皮质血脑屏障毛细血管进行定量的形态分析。结果：脑血流量在GFI过程中降至闭塞前的6%。这与昏迷和去大脑僵直有关。在再灌流期间，短暂充血(225+/-18%，P<；0.001)的特征是颅内压升高(28.3+/-32.6 mm Hg，P<；0.001)和等电脑图。紧随其后的是低灌注率，90分钟时低灌注率从基线水平下降了59.7%(59.7+/-8.8%，P<；0.01)。此时脑电恢复正常，颅内压和平均动脉压均未见异常。到8.5小时，脑血流量恢复正常，这与动物完全恢复相吻合。超微结构血脑屏障分析显示充血时星形胶质细胞足底突起肿胀，毛细血管通畅。低灌注期可见严重的间质血脑屏障水肿和毛细血管腔塌陷。结论：清醒状态下短暂的非致死性GFI再灌注后，周细胞出现双相CBF反应。
OBJECTIVE: In nonrecovery models of cerebral ischemia, blood-brain barrier (BBB) and cerebral blood flow (CBF) changes are known to occur during reperfusion. It is unknown, however, whether those CBF and BBB alterations occur after brief, transient ischemia with neurological recovery. The purpose of this study was to characterize the time course-of CBF and BBB ultrastructural changes during reperfusion in an awake, recovery model of transient global forebrain ischemia (GFI).METHODS: Forty-five adult Sprague-Dawley rats were subjected, while awake, to 10 minutes of GFI by the nine-vessel occlusion method. Thirty-five age-matched animals composed a sham-operated group. Normal control (n = 5), sham-operated (n = 5), and nine-vessel occlusion/reperfusion (n = 15) rats were selected for ultrastructural analysis. Electroencephalography was performed, and CBF, mean arterial blood pressure, and intracranial pressure were measured during ischemia and reperfusion up to 24 hours. Quantitative morphological analysis of cortical BBB capillaries was performed by transmission electron microscopy at the same time points at which specific CBF changes occurred during reperfusion.RESULTS: CBF decreased to 6% of preocclusion values during GFI. This correlated with coma and decerebrate rigidity. During reperfusion, short-lived hyperemia (225 +/- 18%, P < 0.001) was characterized by increased intracranial pressure (28.3 +/- 3 2.6 mm Hg, P < 0.001) and isoelectric electroencephalogram. This was followed by hypoperfusion, which reached a nadir of 59.7% (59.7 +/- 8.8%, P < 0.01) from baseline by 90 minutes. At this time point, the electroencephalogram recovered, and intracranial pressure and mean arterial blood pressure showed no abnormalities. By 8.5 hours, CBF returned to normal, and this coincided with complete recovery of the animal. Ultrastructural BBB analysis revealed astrocyte end-foot process edema and patent capillaries during hyperemia. Severe interstitial BBB edema and capillary lumen collapse was observed during hypoperfusion. Detachment and migration of pericytes was observed during hypoperfusion and beyond.CONCLUSION: A biphasic CBF response is elicited during reperfusion after brief nonlethal GFI under awake conditions.