Xi G, Keep R F, Hoff J T
Department of Surgery (Neurosurgery), University of Michigan, Ann Arbor 48109-0532, USA.
J Neurosurg. 1998 Dec;89(6):991-6. doi: 10.3171/jns.1998.89.6.0991.
The mechanisms of brain edema formation following spontaneous intracerebral hemorrhage (ICH) are not well understood. In previous studies, no significant edema formation has been found 24 hours after infusion of packed red blood cells (RBCs) into the brain of a rat or pig; however, there is evidence that hemoglobin can be neurotoxic. In this study, the authors reexamined the role of RBCs and hemoglobin in edema formation after ICH.
The experiments involved infusion of whole blood, packed RBCs, lysed RBCs, rat hemoglobin, or thrombin into the right basal ganglia of Sprague-Dawley rats. The animals were killed at different time points and brain water and ion contents were measured. The results showed that lysed autologous erythrocytes, but not packed erythrocytes, produced marked brain edema 24 hours after infusion and that this edema formation could be mimicked by hemoglobin infusion. Although infusion of packed RBCs did not produce dramatic brain edema during the first 2 days, it did induce a marked increase in brain water content 3 days postinfusion. Edema formation following thrombin infusion peaked at 24 to 48 hours. This is earlier than the peak in edema formation that follows ICH, suggesting that there is a delayed, nonthrombin-mediated, edemogenic component of ICH.
These results demonstrate that RBCs play a potentially important role in delayed edema development after ICH and that RBC lysis and hemoglobin toxicity may be useful targets for therapeutic intervention.
自发性脑出血（ICH）后脑水肿形成的机制尚未完全明确。在以往的研究中，向大鼠或猪脑内输注浓缩红细胞（RBCs）24小时后未发现明显的水肿形成；然而，有证据表明血红蛋白可能具有神经毒性。在本研究中，作者重新探讨了RBCs和血红蛋白在ICH后水肿形成中的作用。
实验将全血、浓缩RBCs、裂解的RBCs、大鼠血红蛋白或凝血酶注入Sprague-Dawley大鼠的右侧基底神经节。在不同时间点处死动物并测量脑含水量和离子含量。结果显示，输注裂解的自体红细胞而非浓缩红细胞在24小时后可产生明显的脑水肿，且这种水肿形成可通过输注血红蛋白来模拟。虽然输注浓缩RBCs在最初2天内未产生显著的脑水肿，但在输注后3天确实导致脑含水量显著增加。凝血酶输注后的水肿形成在24至48小时达到峰值。这早于ICH后水肿形成的峰值，提示ICH存在延迟的、非凝血酶介导的致水肿成分。
这些结果表明，RBCs在ICH后延迟性水肿发展中可能起重要作用，RBC裂解和血红蛋白毒性可能是治疗干预的有效靶点。
