Li Jie, McAllister James P, Shen Yimin, Wagshul Mark E, Miller Janet M, Egnor Michael R, Johnston Miles G, Haacke E Mark, Walker Marion L
Department of Pediatric Neurosurgery, Children's Hospital of Michigan, Detroit, MI, USA.
Exp Neurol. 2008 Jun;211(2):351-61. doi: 10.1016/j.expneurol.2007.12.030. Epub 2008 Jan 26.
Communicating hydrocephalus (CH) occurs frequently, but clinically-relevant animal models amenable to diagnostic imaging and cerebrospinal fluid shunting are not available. In order to develop and characterize models of subarachnoid space (SAS) obstruction at the basal cisterns (BC) or cerebral convexities (CX), 25% kaolin was injected in adult female Sprague-Dawley rats following halothane anesthesia; intact- or saline-injected animals served as controls. For BC animals (n=28 hydrocephalics, n=20 controls), an anterior approach to the C1-clivus interval was employed and 30 microl of kaolin or saline was injected. For CX injections (n=13 hydrocephalics, n=3 controls), 50-60 microl of kaolin was injected bilaterally after separating the partitions in the SAS. In BC-injected rats, kaolin was observed grossly in the basal cisterns but not in the cisterna magna or at the foramina of Luschka, indicating that communicating (or extra-ventricular)--not obstructive--hydrocephalus had been induced. Following ketamine/xylazine anesthesia, magnetic resonance imaging (MRI) of gadolinium injected into the lateral ventricle also demonstrated CSF flow from the foramina of Luschka. MRI also revealed that ventriculomegaly progressed steadily in BC animals and by 2 weeks post-kaolin the mean Evan's ratio (frontal horn) increased significantly (mean 0.45 compared to 0.31 in intact- and 0.34 in saline-injected controls; p<0.001 for each). CX animals exhibited kaolin deposits covering approximately 80% of the cerebral hemispheres and developed noticeable ventriculomegaly (mean Evan's ratio 0.40), which was significant relative to intact animals (p=0.011) but not saline-injected controls. Surprisingly, ventriculomegaly following CX injections was less severe and much more protracted, requiring 3-4 months to develop compared to ventriculomegaly produced by BC obstruction. No hydrocephalic animals demonstrated obvious neurological deficits, but BC-injected animals that subsequently developed more severe ventriculomegaly exhibited nasal discharges and "coughing" for several days following kaolin injection. The new BC model is relevant because the clinical presentation of CH in children is often associated with obstruction at this site, while the CX model may be more representative of late adult onset normal pressure hydrocephalus.
交通性脑积水(CH)很常见,但目前尚无适用于诊断性成像和脑脊液分流的具有临床相关性的动物模型。为了建立和描述基底池(BC)或脑凸面(CX)蛛网膜下腔(SAS)梗阻模型,在氟烷麻醉下,向成年雌性Sprague-Dawley大鼠注射25%的高岭土;完整或注射生理盐水的动物作为对照。对于BC组动物(28只脑积水大鼠,20只对照),采用C1-斜坡间隙前方入路,注射30微升高岭土或生理盐水。对于CX组注射(13只脑积水大鼠,3只对照),在分离SAS中的分隔后双侧注射50-60微升高岭土。在BC注射的大鼠中,在基底池中肉眼可见高岭土,但在枕大池或Luschka孔中未见,这表明诱导的是交通性(或脑室外)而非梗阻性脑积水。在氯胺酮/赛拉嗪麻醉后,向侧脑室注射钆的磁共振成像(MRI)也显示脑脊液从Luschka孔流出。MRI还显示,BC组动物脑室扩大稳步进展,高岭土注射后2周,平均Evan比率(额角)显著增加(平均0.45,完整对照组为0.31,注射生理盐水对照组为0.34;每组p<0.001)。CX组动物高岭土沉积物覆盖约80%的大脑半球,并出现明显的脑室扩大(平均Evan比率0.40),相对于完整动物有显著性差异(p=0.011),但与注射生理盐水对照组相比无差异。令人惊讶的是,CX组注射后脑室扩大程度较轻且进展更为缓慢,与BC组梗阻导致的脑室扩大相比,需要3-4个月才能形成。没有脑积水动物表现出明显的神经功能缺损,但BC组注射动物中随后出现更严重脑室扩大的动物在高岭土注射后数天出现鼻分泌物和“咳嗽”。新的BC模型具有相关性,因为儿童CH的临床表现通常与此部位梗阻有关,而CX模型可能更代表成人晚期发病的正常压力脑积水。