Wagner K R, Xi G, Hua Y, Kleinholz M, de Courten-Myers G M, Myers R E, Broderick J P, Brott T G
Department of Neurology, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA.
Stroke. 1996 Mar;27(3):490-7. doi: 10.1161/01.str.27.3.490.
The mechanisms underlying brain injury from intracerebral hemorrhage (ICH) are complex and poorly understood. To comprehensively examine pathophysiological and pathochemical alterations after ICH and to examine the effects of hematoma removal on these processes, we developed a physiologically controlled, reproducible, large-animal model of ICH in pigs (weight, 6 to 8 kg).
We produced lobar hematomas by pressure- controlled infusions of 1.7 mL of autologous blood into the right frontal hemispheric white matter over 15 minutes. We froze brains in situ at 1, 3, 5, and 8 hours after hematoma induction and cut coronal sections of hematoma assessment, morphological brain examination, and immunohistochemical and water content determinations.
At 1 hour after blood infusion, "translucent" white matter areas were present directly adjacent to the hematoma. These markedly edematous regions had a greater than 10% increase in water content (>85%) compared with the contralateral white matter (73%), and this increased water content persisted through 8 hours. In addition, these areas were strongly immunoreactive for serum proteins. Intravascular Evans blue dye failed to penetrate into the brain tissue at all time points, demonstrating that this serum protein accumulation and edema development were not due to increased blood-brain barrier permeability.
Experimental lobar ICH in pigs models a prominent pathological feature of human ICH, ie, early perihematomal edema. Our findings suggest that serum proteins, originating from the hematoma, accumulate in adjacent white matter and result in rapid and prolonged edema after ICH. This interstitial edema likely corresponds to the low densities on CT scans and the hyperintensities on T2-weighted MR images that surround intracerebral hematomas acutely after human ICH.
脑出血（ICH）所致脑损伤的机制复杂，目前尚不清楚。为全面研究脑出血后的病理生理和病理化学改变，并探讨血肿清除对这些过程的影响，我们建立了一种生理状态可控、可重复的大型猪脑出血动物模型（体重6至8千克）。
通过在15分钟内将1.7毫升自体血经压力控制注入右侧额叶白质来制造脑叶血肿。在血肿形成后1、3、5和8小时将脑原位冷冻，并制作冠状切片用于血肿评估、脑形态学检查、免疫组织化学及含水量测定。
输血后1小时，血肿紧邻区域出现“半透明”白质区。与对侧白质（73%）相比，这些明显水肿区域的含水量增加超过10%（>85%），且这种含水量增加持续至8小时。此外，这些区域对血清蛋白呈强免疫反应性。在所有时间点，血管内伊文思蓝染料均未渗入脑组织，表明这种血清蛋白积聚和水肿形成并非由于血脑屏障通透性增加所致。
猪实验性脑叶脑出血模拟了人类脑出血的一个突出病理特征，即早期血肿周围水肿。我们的研究结果表明，源自血肿的血清蛋白积聚在相邻白质中，导致脑出血后迅速且持续的水肿。这种间质性水肿可能与人类脑出血后急性期脑内血肿周围CT扫描上的低密度影及T2加权磁共振图像上的高信号影相对应。
