Okauchi Masanobu, Xi Guohua, Keep Richard F, Hua Ya
R5018 Biomedical Science Research Building, Department of Neurosurgery, University of Michigan, 109 Zina Pitcher Place, Ann Arbor, Michigan 48109-2200, USA.
Brain Res. 2009 Jan 16;1249:229-36. doi: 10.1016/j.brainres.2008.10.035. Epub 2008 Oct 28.
Neurodegeneration occurs after intracerebral hemorrhage (ICH) and tissue-type transglutaminase (tTG) has a role in neurodegenerative disorders. The present study investigated tTG expression after ICH and the effects of a tTG inhibitor, cystamine, on ICH-induced brain edema and neurological deficits. This study has two parts. In the first, male Sprague-Dawley rats received an intracaudate injection of 100 microL autologous whole blood or a needle insertion (sham). Rats were killed 3 days later and the brains used for immunohistochemistry, Western blots and real-time quantitative polymerase chain reaction. In the second set, ICH rats were treated intraperitoneally with either a tTG inhibitor, cystamine, or vehicle. Rats underwent behavioral testing and were killed at day-3 for measurement of brain swelling. tTG positive cells were found in the ipsilateral basal ganglia after ICH and most of those cells were neuron-like. Western blot analysis showed a 3-fold increase in tTG in the ipsilateral basal ganglia (p<0.01 vs. sham) after ICH. tTG mRNA levels were also significantly higher (8.5-fold increase vs. sham). Cystamine treatment attenuated ICH-induced brain swelling (day 3: 14.4+/-3.2 vs. 21.4+/-4.0% in vehicle-treated rats, p<0.01), neuronal death and improved functional outcome (forelimb placing score: 47+/-23 vs. 17+/-16% in vehicle-treated rats, p<0.05). ICH induces perihematomal tTG upregulation and cystamine, a tTG inhibitor, reduces ICH-induced brain swelling and neurological deficits.
脑出血（ICH）后会发生神经退行性变，组织型转谷氨酰胺酶（tTG）在神经退行性疾病中起作用。本研究调查了脑出血后tTG的表达情况，以及tTG抑制剂胱胺对脑出血诱导的脑水肿和神经功能缺损的影响。本研究分为两部分。第一部分，雄性Sprague-Dawley大鼠接受尾状核内注射100微升自体全血或进行针穿刺（假手术）。3天后处死大鼠，取脑进行免疫组织化学、蛋白质免疫印迹和实时定量聚合酶链反应检测。第二组实验中，脑出血大鼠腹腔注射tTG抑制剂胱胺或赋形剂。对大鼠进行行为测试，并在第3天处死以测量脑肿胀情况。脑出血后在同侧基底神经节发现tTG阳性细胞，其中大多数细胞类似神经元。蛋白质免疫印迹分析显示，脑出血后同侧基底神经节tTG增加了3倍（与假手术组相比，p<0.01）。tTG mRNA水平也显著升高（与假手术组相比增加了8.5倍）。胱胺治疗减轻了脑出血诱导的脑肿胀（第3天：胱胺治疗组为14.4±3.2%，赋形剂治疗组为21.4±4.0%，p<0.01）、神经元死亡，并改善了功能结局（前肢放置评分：胱胺治疗组为47±23%，赋形剂治疗组为17±16%，p<0.05）。脑出血诱导血肿周围tTG上调，tTG抑制剂胱胺可减轻脑出血诱导的脑肿胀和神经功能缺损。
