Memezawa H, Minamisawa H, Smith M L, Siesjö B K
Department of Neurobiology, University Hospital, Lund, Sweden.
Exp Brain Res. 1992;89(1):67-78. doi: 10.1007/BF00229002.
It has become increasingly clear that a stroke lesion usually consists of a densely ischemic focus and of perifocal areas with better upheld flow rates. At least in rats and cats, some of these perifocal ("penumbral") areas subsequently become recruited in the infarction process. The mechanisms may involve an aberrant cellular calcium metabolism and enhanced production of free radicals. In general, though, the metabolic perturbation in the penumbra requires better characterization. The objective of this article was to define flow distribution in a rat model of reversible middle cerebral artery (MCA) occlusion, so as to allow delineation of the metabolic aberrations responsible for the subsequent infarction. We modified the intraluminal filament occlusion model recently developed by Koizumi et al. (1986), and described in more detail by Nagasawa and Kogure (1989), adopting it for use in both spontaneously breathing and artificially ventilated rats. Successful occlusion of the MCA (achieved in about 9/10 rats) was judged by unilateral EEG depression in ventilated rats, and neurological deficits, such as circling, in spontaneously breathing ones. CBF in the ipsilateral hemisphere was reduced to nearly constant values after 20, 60, and 120 min of occlusion, flow rates in the focus being about 10% and in the perifocal ipsilateral areas about 15-20% of control (contralateral side). When the filament was left in place (permanent occlusion) 2,3,5-triphenyl tetrazolium chloride (TTC) staining and histopathology after 24 h showed a massive infarct on the occluded side, extending from caudoputamen and overlaying cortex to the occipital striate cortex. Animals recirculated after 60 min of MCA occlusion, and allowed to survive 7 days for histopathology, showed infarction of the caudoputamen (lateral part or whole nucleus) in 5/6 animals and selective neuronal necrosis in one animal. The neocortex showed either infarcts, selective neuronal necrosis, or no damage. There was some overlap between neocortical areas which were infarcted and those which were salvaged by reperfusion. In general, though, both the CBF data and the recovery studies with a histopathological endpoint define large parts of the neocortex as perifocal (penumbral) areas which lend themselves to studies of metabolic events leading to infarction.
越来越清楚的是，中风病灶通常由一个密集的缺血灶和周围血流灌注较好的区域组成。至少在大鼠和猫中，这些周围（“半暗带”）区域中的一些随后会在梗死过程中被累及。其机制可能涉及异常的细胞钙代谢和自由基产生增加。不过总体而言，半暗带中的代谢紊乱需要更好地加以描述。本文的目的是确定可逆性大脑中动脉（MCA）闭塞大鼠模型中的血流分布，以便描绘出导致后续梗死的代谢异常情况。我们对小泉等人（1986年）最近开发并由长泽和小暮（1989年）更详细描述的管腔内丝线闭塞模型进行了改进，将其应用于自主呼吸和人工通气的大鼠。在通气大鼠中，通过单侧脑电图抑制来判断MCA是否成功闭塞（约9/10的大鼠可实现），在自主呼吸的大鼠中则通过诸如转圈等神经功能缺损来判断。闭塞20、60和120分钟后，同侧半球的脑血流量降至近乎恒定的值，病灶处的血流速度约为对照（对侧）的10%，同侧周围区域的血流速度约为对照的15 - 20%。当丝线留置原位（永久性闭塞）时，24小时后进行的2,3,5 - 三苯基氯化四氮唑（TTC）染色和组织病理学检查显示，闭塞侧出现大面积梗死，从尾壳核和覆盖的皮质延伸至枕纹状皮质。在MCA闭塞60分钟后再灌注并存活7天以进行组织病理学检查的动物中，5/6的动物出现尾壳核梗死（外侧部分或整个核），1只动物出现选择性神经元坏死。新皮质要么出现梗死、选择性神经元坏死，要么未受损。梗死的新皮质区域和通过再灌注得以挽救的区域之间存在一些重叠。不过总体而言，脑血流量数据和以组织病理学为终点的恢复研究都将大部分新皮质定义为周围（半暗带）区域，这些区域适合用于研究导致梗死的代谢事件。
