Department of Physiology and Pharmacology, Loma Linda University, Loma Linda, California, United States of America.
PLoS One. 2013 Jul 23;8(7):e69571. doi: 10.1371/journal.pone.0069571. Print 2013.
Chronic communicating hydrocephalus is a significant health problem affecting up to 20% of survivors of spontaneous subarachnoid hemorrhage (SAH). The development of new treatment strategies is hampered by the lack of well characterized disease models. This study investigated the incidence of chronic hydrocephalus by evaluating the temporal profile of intracranial pressure (ICP) elevation after SAH, induced by endovascular perforation in rats. Twenty-five adult male Sprague-Dawley rats (260-320 g) were subjected to either endovascular perforation or sham surgery. Five animals died after SAH induction. At 7, 14 and 21 days after surgery ICP was measured by stereotaxic puncture of the cisterna magna in SAH (n=10) and SHAM (n=10) animals. On day 21 T-maze test was performed and the number of alterations and latency to decision was recorded. On day 23, samples were processed for histological analyses. The relative ventricle area was evaluated in coronal Nissl stained sections. On day 7 after surgery all animals showed normal ICP. The absolute ICP values were significantly higher in SAH compared to SHAM animals on day 21 (8.26±4.53 mmHg versus 4.38±0.95 mmHg) but not on day 14. Observing an ICP of 10 mmHg as cut-off, 3 animals showed elevated ICP on day 14 and another animal on day 21. The overall incidence of ICP elevation was 40% in SAH animals. On day 21, results of T-maze testing were significantly correlated with ICP values, i.e. animals with elevated ICP showed a lower number of alterations and a delayed decision. Histology yielded a significantly higher (3.59 fold increased) relative ventricle area in SAH animals with ICP elevation compared to SAH animals without ICP elevation. In conclusion, the current study shows that experimental SAH leads to chronic hydrocephalus, which is associated with ICP elevation, behavioral alterations and ventricular dilation in about 40% of SAH animals.
慢性交通性脑积水是一个严重的健康问题,影响到自发性蛛网膜下腔出血(SAH)幸存者的 20%。由于缺乏特征明确的疾病模型,新的治疗策略的发展受到阻碍。本研究通过评估血管内穿孔诱导的 SAH 大鼠颅内压(ICP)升高的时间进程,研究了慢性脑积水的发生率。25 只成年雄性 Sprague-Dawley 大鼠(260-320g)接受血管内穿孔或假手术。SAH 诱导后有 5 只动物死亡。术后第 7、14 和 21 天,通过立体定向穿颅术测量 SAH(n=10)和 SHAM(n=10)动物的脑池压力。第 21 天进行 T 迷宫测试,记录改变次数和决策潜伏期。第 23 天,进行组织学分析。在冠状 Nissl 染色切片中评估相对脑室面积。术后第 7 天,所有动物的 ICP 均正常。SAH 动物的绝对 ICP 值在第 21 天明显高于 SHAM 动物(8.26±4.53mmHg 与 4.38±0.95mmHg),但在第 14 天没有差异。当 ICP 为 10mmHg 作为截止值时,3 只动物在第 14 天和另一只动物在第 21 天出现 ICP 升高。SAH 动物的 ICP 升高总发生率为 40%。第 21 天,T 迷宫测试的结果与 ICP 值显著相关,即 ICP 升高的动物改变次数较少,决策延迟。组织学显示,ICP 升高的 SAH 动物的相对脑室面积明显高于无 ICP 升高的 SAH 动物(增加 3.59 倍)。总之,本研究表明,实验性 SAH 导致约 40%的 SAH 动物出现慢性脑积水,其特征是 ICP 升高、行为改变和脑室扩张。