Nagaraja Tavarekere N, Keenan Kelly A, Brown Stephen L, Fenstermacher Joseph D, Knight Robert A
Department of Anesthesiology, Henry Ford Health System, Detroit, MI, USA.
Neurol Res. 2007 Jan;29(1):78-80. doi: 10.1179/174313206X153815.
Acute blood-brain barrier (BBB) opening in cerebral ischemia is an often observed but seldom studied phenomenon. Increased permeability has been implicated with several consequences including exacerbating ischemic injury, leading to hemorrhagic transformation (HT) and also predictive of chronic damage and a way of delivering therapeutics to the diseased parts of brain. Very few studies have investigated the 'size' of such acute openings. Herein the blood-brain distribution of fluorescent isothiocyanate (FITC)- labeled red blood cells (RBCs; approximately 5 tm in diameter) and two different sized plasma flow markers in cerebral microvessels was studied by laser scanning confocal microscopy (LSCM) 6 and 24 hours after the onset of a 3 hour period of focal ischemia. At hour 6, Evans blue-tagged albumin [EB-Alb; molecular weight (MW)= 68 kDa, Stokes-Einstein radius=37 A], a marker of both plasma flow and BBB opening, was seen both inside and around microvessels whereas the RBCs were only intravascular. FITC-labeled dextran (FITC-dextran; MW=2000 kDa, Stokes-Einstein radius = approximately 150 A), another plasma flow tracer, had not leaked across the BBB into the tissue at this time. At hour 24, both RBCs and FITC-dextran were found extravascularly along with EB-Alb. We postulate that smaller sized openings in BBB at hour 6 limited the leaking of the two large tracers (RBCs and FITC-dextran) and that such size-dependency was lost by 24 hours with the progression of the ischemic injury.
脑缺血时急性血脑屏障（BBB）开放是一种常见但很少被研究的现象。通透性增加与多种后果相关，包括加重缺血性损伤、导致出血性转化（HT），还可预测慢性损伤以及作为向脑病变部位递送治疗药物的一种方式。很少有研究调查这种急性开放的“大小”。在此，通过激光扫描共聚焦显微镜（LSCM）研究了局灶性缺血3小时发作后6小时和24小时，荧光异硫氰酸酯（FITC）标记的红细胞（RBCs；直径约5μm）以及两种不同大小的脑微血管血浆流动标记物在血脑之间的分布。在6小时时，伊文思蓝标记的白蛋白[EB - Alb；分子量（MW）= 68 kDa，斯托克斯 - 爱因斯坦半径 = 37 Å]，一种血浆流动和血脑屏障开放的标记物，在微血管内部和周围均可见，而红细胞仅在血管内。FITC标记的葡聚糖（FITC - dextran；MW = 2000 kDa，斯托克斯 - 爱因斯坦半径约为150 Å），另一种血浆流动示踪剂，此时尚未透过血脑屏障泄漏到组织中。在24小时时，红细胞和FITC - 葡聚糖与EB - Alb一起出现在血管外。我们推测，6小时时血脑屏障中较小尺寸的开放限制了两种大分子示踪剂（红细胞和FITC - 葡聚糖）的泄漏，并且随着缺血性损伤的进展，这种尺寸依赖性在24小时时消失。
