New mutant mouse with communicating hydrocephalus and secondary aqueductal stenosis

Summary A new mutation resulting in hydrocephalus in the mouse is described. Inheritance is autosomal recessive. The disease becomes evident a few days after birth by the presence of generalized ventricular dilatation. This early phase is followed after 2 weeks of age by a phase of superimposed aqueductal stenosis, which appears to be secondary to compression of the midbrain by the expanding cerebral hemispheres. Affected animals usually die by 1 month of age.Golgi studies demonstrate damage to the cerebral cortex in both phases of the pathological process. The hemispheric white matter is more severely disrupted. Horseradish peroxidase, a protein tracer demonstrable by electron microscopy, enters the intercellular spaces of the brain in the normal manner by passing between ependymal cells after it is injected into a lateral cerebral ventricle. Scanning electron microscopy revealed large numbers of macrophages and red blood cells on the ventricular surface of the hydrocephalic brain.Review of the literature suggests that some types of human hydrocephalus may exhibit a similar sequence of generalized ventricular enlargement followed secondarily by compression of the midbrain with resultant aqueductal stenosis.Supported by Research Grant 1 RO1 NS 08359 and Special Felowship 7 F11 NS 1968-02 from the National Institute of Neurological Diseases and Stroke, U. S. Public Health Service.     

Neocortical capillary flow pulsatility is not elevated in experimental communicating hydrocephalus

While communicating hydrocephalus (CH) is often characterized by increased pulsatile flow of cerebrospinal fluid (CSF) in the cerebral aqueduct, a clear-cut explanation for this phenomenon is lacking. Increased pulsatility of the entire cerebral vasculature including the cortical capillaries has been suggested as a causative mechanism. To test this theory, we used two-photon microscopy to measure flow pulsatility in neocortical capillaries 40 to 500 μm below the pial surface in adult rats with CH at 5 to 7 days (acute, n=8) and 3 to 5 weeks (chronic, n=5) after induction compared with intact controls (n=9). Averaging over all cortical depths, no increase in capillary pulsatility occurred in acute (pulsatility index (PI): 0.15±0.06) or chronic (0.14±0.05) CH animals compared with controls (0.18±0.07; P=0.07). More specifically, PI increased significantly with cortical depth in controls (r=0.35, P<0.001), but no such increase occurred in acute (r=0.06, P=0.3) or chronic (r=0.05, P=0.5) CH. Pulsatile CSF aqueductal flow, in contrast, was elevated 10- to 500-fold compared with controls. We conclude that even in the presence of markedly elevated pulsatile CSF flow in the aqueduct, there is no concurrent increase in microvascular pulsatile flow.     

The microglial response to progressive hydrocephalus in a model of inherited aqueductal stenosis

Abstract

Although gliosis has been reported to be a common and persistent feature in the white matter of hydrocephalic brains, no studies have identified the cell types that characterize this response. Therefore, the present study has employed histochemical methods to evaluate microglial cells in the brains of infant rats with inherited hydrocephalus. This strain of rats acquires hydrocephalus during late fetal stages due to aqueductal stenosis. Tissue from the sensorimotor and auditory cortices of 12- and 21-day-old hydrocephalic and normal H-Tx rats was processed and stained for the lectin microglial marker Griffania simplicifolia (GSA-IB4). During the progression of hydrocephalus, GSA-positive cells exhibited three changes: (7) Cytologically, the cell bodies were enlarged, and their processes were thicker, longer. and more numerous. These changes were most notable in the gray matter. (2) The packing density of GSApositive cells was either increased or decreased, depending on the age of the animal and the severity of hydrocephalus. (3) Localized clusters of GSA-positive cells were conspicuous in the white matter of 12-day animals with mild hydrocephalus, and in the gray matter of 21-day animals with severe hydrocephalus. These results indicate that the microglial response is initiated during intermediate stages of hydrocephalus, and is not restricted to the periventricular white matter. These changes may signal other pathophysiologic events in the hydrocephalic brain, and demonstrate that microglia constitute one important element in the gliosis that accompanies hydrocephalus. [Neural Res 1998; 20: 697-704]     

Young C3H mice infected with Toxoplasma gondii are a novel experimental model of communicating hydrocephalus

The effects of leptomeningeal inflammation on the development of hydrocephalus are less understood than those of obstructing the flow of cerebrospinal fluid (CSF) in animal models. We succeeded in introducing a novel experimental model of hydrocephalus and analysed changes in histopathology and CSF flow in mice infected with an avirulent Fukaya strain of Toxoplasma gondii (T. gondii). Six to 7 week-old male mice were orally inoculated with a brain homogenate containing ten T. gondii cysts. The cerebral ventricles became enlarged in all C3H/HeN and C57BL/6 mice 4 weeks after T. gondii infection, but mildly in BALB/c mice. In addition to the lateral ventricle, the third and fourth ventricles and Sylvian aqueducts were dilated in all mice. Lymphocytes and monocytes infiltrated the subarachnoid space. Indian ink particles required more time to pass from the lateral ventricle to the cervical lymph nodes, although they reached the subarachnoid space. Computed tomography ventriculography demonstrated that the CSF was not obstructed during passage through the ventricular systems, but contrast remained static in the lateral ventricle only in infected mice. These results indicated that the infected mice developed communicating type hydrocephalus without obstructive or mass lesions in the ventricles. The hydrocephalus that arises in mice infected with T. gondii is considered a consequence of leptomeningeal inflammation that blocks CSF circulation at the subarachnoid space, implying that leptomeningeal inflammation is important in other types of hydrocephalus.     

Congenital hydrocephalus: A new experimental model with histopathological study

We describe a new experimental model of fetal hydrocephalus in the lamb. 14 sheep were operated on at 100–120 days gestation for the insertion of a catheter into the fetal aqueduct of Sylvius, to block cerebrospinal fluid (CSF) flow. After the operation the intracranial pressure (ICP) was measured daily from the distal end of the catheter. The progress of ventricular dilatation was recorded by ultrasound. At ICP 100 mm/H²O the animals were killed for postmortem examination of the fetuses. Neuropathological examination showed massive dilatation of the ventricles. The ependymal cells appeared to be flat and the cellular lining disrupted. Growth of pseudocysts, cellular stratification and proliferation of the paraventricular germinal cells were observed also. With our new experimental model we were able to control the rise in ICP and correlate the evolution of the anatomical damage with the duration of high ICP and with the gestational age at which it began. Our model can also be used at early stages of gestation for reversing the development of hydrocephalus. It might therefore provide information on the suitability of fetal hydrocephlus surgery.

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Sommario Gli AA. presentano un modello sperimentale di idrocefalo fetale ottenuto in pecore gravide al 100° giorno di gestazione, introducendo un catetere nell’acquedotto di Silvio. L’idrocefalo viene monitorizzato mediante ultrasuoni e la misurazione della pressione del liquido cerebrospinale. Gli animali vengono sacrificati quando la pressione intracranica raggiunge i 100 mm di H₂O. Lo studio neuropatologico, rispetto a casi di controllo a periodi di età gestazionale, evidenzia una marcata dilatazione dei ventricoli, un appiattimento dello strato cellulare ependimale, una proliferazione delle cellule germinali periventricolari, presenza di pseudorosette cellulari nella sostanza bianca subependimale.

     

Parkinsonian syndrome in the course of aqueductal stenosis hydrocephalus

Report of a case of hydrocephalus secondary to stenosis of the aqueduct with associated parkinsonian syndrome. The suggested etiopathogenesis: damage to the striatal system favored by underlying weakness of the basal ganglia.

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Sommario Gli Autori descrivono un caso di idrocefalo da stenosi dell'acquedotto associato ad una sintomatologia parkinsoniana. Successivamente, ne espongono la possibile ipotesi eziopatogenetica: compromissione del sistema striatale favorita da una condizione predisponente di labilità dei nuclei della base.

     

神经内镜下导水管成形术治疗导水管梗阻性脑积水

目的 探讨软性神经内镜下导水管成形术治疗导水管梗阻性脑积水的应用价值.方法 2007年2月至2008年4月,应用电子软性神经内镜对16例导水管梗阻性脑积水在软性内镜下分别经额或枕下入路行导水管成形术.结果 16例患者导水管均成功再通,术后高颅压症状缓解,无意识障碍、动眼神经麻痹等导水管成形术相关并发症出现.12例术后6个月磁共振电影成像检查显示中脑导水管脑脊液最大流速较术前增加(2.18±0.34)cm/s,最大流量较术前增加(0.22±0.07)ml/s.结论 软性内镜下导水管成形术对治疗导水管狭窄或膜性梗阻导致的脑积水是一种安全有效的方法 ,但应严格掌握手术适应证.     

Recurrent thyrotoxicosis and papilledema in a patient with communicating hydrocephalus

A patient with communicating hydrocephalus had recurrent papilledema during episodes of thyrotoxicosis. Increased intracranial pressure was documented and, as reflected by the severity of the papilledema, fluctuated in proportion to the thyroid hormone levels.     

A murine model of communicating hydrocephalus: Role of TGF-beta1

Subarachnoid haemorrhage (SAH) often causes communicating hydrocephalus. We recently found that intrathecal injection of human recombinant transforming growth factor (hrTGF)-beta1 induced communicating hydrocephalus in mice. In this experiment we examined whether hydrocephalus could be generated in mice by intrathecal injection of autologous serum, which would contain TGF-beta1 in a similar situation to SAH. Mouse serum, plasma and a range of quantities of hrTGF-beta1 were injected intrathecally into 10 day old C57BL/6 mice. The sizes of the lateral ventricles were measured some weeks after injection. The serum induced hydrocephalus which was prevented by additional injection of anti-TGF-beta1 antibody. Immunoblot analysis showed a band of the active form of TGF-beta1 in the serum which was not detected in the plasma. This study therefore suggests that active TGF-beta1 in cerebrospinal fluid after SAH contributes to the generation of communicating hydrocephalus.     

A new experimental model of obstructive hydrocephalus in the rat: the micro-balloon technique

We used three types of specialized micro-balloons 0.7–1.35 mm in outer diameter instead of kaolin to develop a reproducible rat model of hydrocephalus with a low experimental mortality. The micro-balloon was inserted 6 mm deep into the cisterna magna via a burr hole immediately behind the lambda. The angle of introduction was 50°. We also set up kaolin-induced hydrocephalic models in 25 rats as controls. The kaolin model revealed 52% mortality with an 80% induction rate of hydrocephalus, while the balloon model showed 9% mortality with a 60% induction rate. Balloon-induced hydrocephalus was maximal at 1 week and tended to decrease after 2–3 weeks. The pathological findings were not different between the two models. We concluded that the micro-balloon model for hydrocephalus is an easily reproducible model with low experimental mortality. Received: 2 March 1998 Revised: 21 July 1998     

脑室冲洗与常规脑脊液置换在脑脊液蛋白增高脑积水中的比较研究

目的比较脑室冲洗与常规脑脊液置换在脑脊液蛋白增高脑积水中的应用价值。方法选取我院2015年1月至2018年8月确诊为脑脊液蛋白增高脑积水病人90例。随机分成脑室冲洗组、脑室外引流组和腰大池外引流组,每组30例。脑室冲洗组行两侧脑室冲洗;脑室及腰大池外引流组行脑室和腰大池引流,3组病人脑脊液蛋白500 mg/L后行脑室腹腔分流术。观察术后7 d、14 d脑脊液蛋白含量、等待分流手术的时间、颅内感染及堵管发生率。结果脑室冲洗组等待分流手术的时间1.87 d,明显短于两常规组(P0.01),术后7 d脑脊液蛋白含量523.45 mg/L,明显高于两对照组(P0.05),14 d后无明显差异。脑室外引流组颅内感染发生率30%,明显高于脑室冲洗组(P0.05)。3组堵管发生率没有明显差异。结论脑室冲洗能明显加快脑脊液蛋白增高脑积水病人的手术进程,值得推广应用。     

脑室冲洗与常规脑脊液置换在脑脊液蛋白增高脑积水中的比较研究

目的 比较脑室冲洗与常规脑脊液置换在脑脊液蛋白增高脑积水中的应用价值。方法 选取我院2015年1月至2018年8月确诊为脑脊液蛋白增高脑积水病人90例。随机分成脑室冲洗组、脑室外引流组和腰大池外引流组，每组30例。脑室冲洗组行两侧脑室冲洗；脑室及腰大池外引流组行脑室和腰大池引流，3组病人脑脊液蛋白﹤500 mg/L后行脑室腹腔分流术。观察术后7 d、14 d脑脊液蛋白含量、等待分流手术的时间、颅内感染及堵管发生率。结果 脑室冲洗组等待分流手术的时间1.87 d，明显短于两常规组（P<0.01），术后7 d脑脊液蛋白含量523.45 mg/L，明显高于两对照组（P<0.05），14 d后无明显差异。脑室外引流组颅内感染发生率30%，明显高于脑室冲洗组（P<0.05）。3组堵管发生率没有明显差异。结论 脑室冲洗能明显加快脑脊液蛋白增高脑积水病人的手术进程，值得推广应用。