Lindsberg P J, Carpén O, Paetau A, Karjalainen-Lindsberg M L, Kaste M
Department of Neurology, University of Helsinki, Finland.
Circulation. 1996 Sep 1;94(5):939-45. doi: 10.1161/01.cir.94.5.939.
After focal brain ischemia, leukocytes adhere to the perturbed endothelium and are believed to aggravate reperfusion injury. Although ischemia-induced upregulation of endothelial adhesion molecules, intercellular adhesion molecule-1 (ICAM-1) and P-selectin, has been observed in experimental animals, the mechanism of cerebral leukocyte infiltration and thus therapeutic possibilities to reduce it in humans are uncertain.
We counted the granulocytes, mononuclear phagocytes, and the percentages of cerebral microvessels expressing ICAM-1 by applying immunohistochemistry on brain sections showing a variable degree of neuronal damage from 11 human subjects who died 15 hours to 18 days after ischemic stroke and from normal control brains. In infarcted regions, granulocytes were detected as early as at 15 hours after injury (11.3 versus 0.5 cells/mm2 in noninfarcted hemisphere); their amount exceeded 200 cells/mm2 by 2.2 days but was back to normal level at 6.3 and 8.5 days. Acute infarctions (0.6 to 8.5 days) harbored significantly more ICAM-1-stained microvessels (up to 97% of microvessels at 1.8 days) than the noninfarcted hemisphere (P < .001), although the noninfarcted hemisphere (1.8 to 6.3 days) also showed higher ICAM-1 expression than controls. In the absence of ICAM-1 upregulation, macrophages (> 200/mm2) were abundant in the core of neuronal damage at 17 and 18 days.
The striking upregulation of endothelial ICAM-1 expression, functioning in concert with chemotactic factors, may cause granulocyte infiltration during the first 3 days after stroke. This study may support the usage and timing of antibody infusions to block endothelial adhesion molecules in an attempt to reduce leukocyte-induced damage in stroke.
局灶性脑缺血后，白细胞黏附于受损的内皮细胞，被认为会加重再灌注损伤。尽管在实验动物中已观察到缺血诱导的内皮黏附分子、细胞间黏附分子-1（ICAM-1）和P-选择素上调，但脑白细胞浸润的机制以及在人类中减少这种浸润的治疗可能性尚不确定。
我们通过对11例缺血性中风后15小时至18天死亡的人类受试者以及正常对照大脑的脑切片进行免疫组织化学，来计数粒细胞、单核吞噬细胞以及表达ICAM-1的脑微血管百分比，这些脑切片显示出不同程度的神经元损伤。在梗死区域，损伤后15小时即可检测到粒细胞（梗死半球为11.3个细胞/mm²，非梗死半球为0.5个细胞/mm²）；到2.2天时其数量超过200个细胞/mm²，但在6.3天和8.5天时恢复到正常水平。急性梗死（0.6至8.5天）中ICAM-1染色的微血管显著多于非梗死半球（1.8天时高达97%的微血管）（P <.001），尽管非梗死半球（1.8至6.3天）的ICAM-1表达也高于对照组。在没有ICAM-1上调的情况下，17天和18天时巨噬细胞（> 200/mm²）在神经元损伤核心区域大量存在。
内皮ICAM-1表达的显著上调与趋化因子协同作用，可能在中风后的头3天内导致粒细胞浸润。本研究可能支持使用抗体输注并确定其时机，以阻断内皮黏附分子，从而试图减少中风中白细胞诱导的损伤。
