Light and electron microscopic studies of experimental hydrocephalus

Summary A light and electron microscopic study of the ependymal and subependymal regions of experimental hdrocephalic cats was made. Hydrocephalus was induced by injection of kaolin into the cisterna magna. Cerebrospinal fluid (CSF) turnover was measured in all experimental cats by ventricular perfusion just prior to glutaraldehyde fixation. The cats were sacrificed at 7 (acute hydrocephalus) and at 21 or more days (chronic hydrocephalus) after kaolin. The major pathological findings were: flattened and outstretched ependymal lining, detachment of ependymal cells and rarefaction of subependymal areas with increase in the extracellular space. The significant morphological alterations in acute hydrocephalus, characterized by a marked decreased rate of CSF absorption, were flattening and outstretching of ependymal cells with minimal rarefaction of subjacent tissues. In the acute animal with a measurable amount of CSF absorption, and more clearly, in the chronic animal with higher rates of CSF absorption, detachment of ependymal calls, significant rarefaction of subependymal tissues, and marked increased subependymal extracellular space were the predominant changes. It is concluded that these pathological changes provide the morphologic substrate for transventricular absorption of CSF.Supported by USPHS Grants No. NS-08376, NS-06599, and NS-05024.     

The pathology of experimental obstructive hydrocephalus

Summary Obstructive hydrocephalus was produced in 10–14 day-old rabbits by injection of kaolin into the cisterna magna and the ependyma and subependymal tissue was studied by electron microscopy. Generally, the study confirmed recent light microscopic observations on similar models (Torvik et al., 1976). In contrast to most previous reports,it was found that the ependyma adapted remarkably well to ventricular dilatation. No true ependymal defects occurred even in extensive hydrocephalus except at the sites of the ventricular synechiae which sometimes ruptured. The specialized ependymal junctions remained intact but outside the junctions the intercellular clefts were widened, particularly along the lateral wall of the lateral ventricle. The density of the microvilli and cilia decreased, probably because of the increase in the surface area of the ependyma. Dense bundles of filaments developed in the ependymal cells of the hydrocephalic animals.The extracellular space of the subependymal white matter appeared increased but there was no evidence of destruction of fibres or cells. Thus, the reduction of the cerebral mantle thickness was probably mainly caused by pressure atrophy.     

The pathology of experimental obstructive hydrocephalus

Summary Obstructive hydrocephalus was produced in 14-day old rabbits by injection of kaolin into the cisterna magna. The ependymal lining was studied by scanning electron microscopy.Marked hydrocephalus was present 1 or 2 weeks after the kaolin injection. The ependymal lining adapted remarkably well to the rapid expansion by increasing the surface area of the ependymal cells. No breaks or denudement of the ependymal lining was observed except at the sites of ruptured ventricular synechiae. Generally, these findings confirm previous light and electron microscopic observations on the same model (Torvik et al. 1976; Torvik and Stenwig 1977). The results are discussed in relation to current theories concerning the pathophysiology of acute hydrocephalus.     

Increased catecholamine levels in specific brain regions of a rat model of depression: normalization by chronic antidepressant treatment

Alterations in catecholamine levels and neurotransmission have been shown in depressive disorders. However, the exact sites of alterations and the relation between these alterations to the etiology of the disease and the effectiveness of antidepressant therapy are poorly understood. In this study, catecholamine levels and metabolism were measured in specific brain regions of a genetic rat model of depression [Flinders Sensitive Line (FSL) rats], and compared to normal Sprague-Dawley rats. Norepinephrine levels were found to be two to threefold higher in the nucleus accumbens, prefrontal cortex, hippocampus and median raphe nucleus of FSL rats as compared with control Sprague-Dawley rats. Dopamine levels were sixfold higher in the nucleus accumbens and twofold higher in the striatum, hippocampus and hypothalamus of FSL rats as compared with control Sprague-Dawley rats. After chronic treatment with the antidepressant desipramine, the immobility score in a swim test, as a measure of a behavioral deficit, as well as catecholamine levels of the FSL rats became normalized, but these parameters in the control rats did not change. The results indicate that the behavioral deficits expressed in the FSL model for depression correlate with increased catecholamine levels in specific brain sites, and further suggest the FSL rats as a model for elucidation of the molecular mechanism of clinically used antidepressant drugs.     

Cerebral blood flow and metabolism in experimental hydrocephalus

Cerebral blood flow and metabolism were studied in experimental hydrocephalus which was produced by intracisternal injection of kaolin in cats, rabbits and rats. Measurements were carried out in varied stages of hydrocephalus. Local cerebral blood flow (I-CBF) was measured by the hydrogen clearance method. Assessment of cerebral metabolism was made biochemically in the brain tissues of various regions, including water content, Na, K, lactate, pyruvate, lipids, ATP, cyclic AMP, catecholamines and monoamine metabolites. Blood flow studies were performed in the cerebral cortex, periventricular white matter, thalamus and midbrain reticular formation in hydrocephalic cats. In all of these regions, I-CBF decreased to about half of the control in both acute and chronic stages of hydrocephalus. CO₂ reactivity to CBF was impaired only in the acute stage, while autoregulation of CBF was preserved in the hydrocephalic brain. Water content of the brain tissue increased temporarily only within the periventricular white matter of hydrocephalic rabbits concomitant with increase in Na and decrease in K. Transient increase in the lactate and lactate/pyruvate ratios was also observed in the frontal lobe tissue. In hydrocephalic rats, decrease in phospholipids and cholesterol was observed parallel with the degree of ventricular dilatation. ATP and cyclic AMP decreased biphasically in both acute and chronic stages. On the other hand, increase in concentrations of norepinephrine, dopamine, homovanillic acid, and 5-hydroxyindoleacetic acid became evident in the chronic stage of hydrocephalus. From the above results, it is concluded that the hydrocephalic brain sustained considerable disturbance of metabolism in all modalities in association with decreased blood flow, which is sufficient to explain the clinical symptoms of hydrocephalus.     

实验性脑积水轴索细胞骨架的变化

目的探讨脑积水中轴索损伤的发展变化规律.方法以枕大池穿刺注射白陶土的方法建立犬脑积水模型,分为3 d组、2周组、8周组及对照组,每组5只.通过免疫组化方法观察半球白质内轴索的形态变化,并使用电脑图像分析系统定量测定轴索细胞骨架的结构亚单位微管相关蛋白-2(MAP-2)和神经微丝(NF)蛋白亚单位含量.结果①轴索随脑积水发展相继出现扭曲、肿胀、断裂以及轴索球形成等形态学改变;②3 d组MAP-2含量与对照组相比无显著差异(P>0.05),NF蛋白有下降(P<0.05),在2周组和8周组,两者则进行性减少(P<0.05).结论脑积水中的轴索损伤是以细胞骨架破坏为起始的一个渐进过程,它在早期阶段是可逆的,通过综合治疗有望阻断这一过程.     

Analysis of intracranial pressure pulse wave in experimental hydrocephalus

Much has been written about the relationship between the pulse pressure (PP) of the intracranial pressure pulse wave (ICPPW) and ventricle dilatation. Some data suggest that high PP is the cause of ventricle dilatation, and other authors have reported that high PP results from decreased intracranial compliance. In order to clarify these points, the amplitude of PP and pressure-volume response (PVR: an indicator of intracranial complicance) were measured in bilateral ventricles using Hochwald's hydrocephalic model (right-left difference in ventricle size is clear due to hemicraniectomy). Hydrocephalus was induced by means of intracisternal injection of a kaolin powder solution to dogs. The mean ICP, amplitude of the PP, PVR and ventricle size (estimated by MR imaging) were evaluated in pathologic conditions induced by the following procedures. Group A, control: kaolin-induced hydrocephalus without craniectomy; group B: kaolin-induced hydrocephalus with right-sided craniectomy; group C: kaolin-induced hydrocephalus with right-sided craniectomy and dural resection; group D: kaolin-induced hydrocephalus with right-sided craniectomy, dura resection and temporal muscle resection. Using MR imaging, the same degree of symmetrical ventricle dilatation was identified in all groups except group D. Group D alone demonstrated a difference in ventricular size (craniectomy side > non-craniectomy side). There was no appreciable difference in mean ICP between any two groups. However, the amplitude of PP and the PVR decreased stepwise from group A to group D. The difference in the amplitude of the PP and PVR between the right and left ventricles was not significant in any group. Even on the larger ventricle side (right) in group D, the amplitude of PP was the same as that of the left ventricle, and much smaller than in other groups. The results of our research suggest that: (1) There was no relation between ventricle dilatation and the amplitude of PP. This means that the increased amplitude of PP was not the cause of the ventricle dilatation in this model. (2) A high degree of correlation exists between the amplitude of PP and the PVR. This means that PP can be a good parameter of intracranial compliance in this modelPresented at the Consensus Conference: Hydrocephalus '92, Assisi, Italy, 26–30 April 1992     

Cerebral energy metabolism in experimental canine hydrocephalus

Cerebral energy metabolism, its relationship to the stage and extent of hydrocephalus, and the effect of cerebrospinal fluid (CSF) removal on it were studied in experimental canine hydrocephalus produced by intracisternal injection of kaolin by using phosphorus-31 (P-31) magnetic resonance (MR) spectroscopy and MR imaging, P-31 MR spectra were serially obtained before and after CSF removal, maximally on eight occasions over a period of nearly 5 h. There was a decrease in the ratio of creatine phosphate to inorganic phosphate, used as an indicator of the bioenergetic state, in acute and subacute stages of hydrocephalus as compared with the control. An animal in the subacute stage, when periventricular edema was most prominent, exhibited the most predominent decrease in this ratio at 14 days after hydrocephalic insult. The recovery of the ratio toward the control level was seen in the chronically hydrocephalic animal. There was no change in adenosine triphosphate (ATP) levels in any stage of hydrocephalus. Serial spectra obtained after the withdrawal of ventricular CSF showed no change in the bioenergetic state of the brain in any stage of hydrocephalus. There was no relationship between either the extent of hydrocephalus or the ventricular CSF pressure and the change in the bioenergetic state or the levels of any of the phosphorus compounds. These findings may indicate the alteration of the mitochondrial energy metabolism in hydrocephalus, which may explain the mechanism of hydrocephalic syndrome.     

Experimental hydrocephalus

Summary SD-JCL rats were injected with 25 mg/kg of ethylnitrosourea on day 9 1/2 of gestation. Fetuses were excised near term and examined under dissecting microscope. 78% of viable fetuses were found to be hydrocephalic. On the histologic study of the serial sections of the brain, a stenosis of the Sylvian aqueduct without subependymal gliosis, edematous choroid plexus with engorged vessels, scanty connective tissue and swollen epithelium, thinning of the telencephalic wall with poorly developed granular layers and the neuroblasts remaining in the ependymal zone, were the characteristic findings in the hydrocephalic fetuses.The natural course of the treated young rats was studied. 75% of the newborn rats showed some clinical evidence of hydrocephalus. Severely affected rats became progressively lethargic and/or paralytic, and died usually before the end of 4th week. Protein content of the cerebrospinal fluid was significantly increased. Subdural, subarachnoid and intraventricular hemorrhages were observed and suspected to be the cause of death.On the histological examination of hydrocephalic youngs, flattening of the ependymal cells and engorgement of the cortical vessels were observed as early as in 2-week-old youngs. In more advanced stages, there was noted the thinning of the periventricular white matter, especially around the occipital horn. The thin pallium showed vacuolization of the perineural tissue, enlargement of the Virchow-Robin space and the status spongiosus-like degeneration. Various types of ependymal proliferation was seen.The present study represents the first postnatal observation of the transplacentally induced congenital hydrocephalus in the rat. The present technique proved to be a simple and reproducible model of producing a congenital hydrocephalus in the rat.Supported in part by a grant from the Ministry of Education (1970–1971).     

Biogenic amines in the human neocortex in patients with neocortical and mesial temporal lobe epilepsy: identification with in situ microvoltammetry

Biogenic amines in well defined subtypes of human temporal lobe epilepsy (TLE) have not been well characterized. Specimens from five patients with neocortical TLE (NTLE) and nine with mesial TLE (MTLE) were immediately placed in Ringer's lactate; stearate indicator microelectrodes were placed in temporal gray matter, Ag/AgCl reference microelectrodes and auxiliary microelectrodes were placed 3-7 mm contralaterally to the indicator microelectrode. Dopamine (DA), ascorbic acid (AA), norepinephrine (NE) and serotonin (5-HT) were identified by their characteristic oxidative potentials in vitro. Four of five patients with NTLE had NE depletion in temporal neocortex while eight of nine patients with MTLE had high concentrations of NE (chi-square P<0.01). Significant concentrations of DA were present in the temporal lobes of three of five NTLE patients but in only one of the nine MTLE patients (chi-square P<0.05). 5-HT was present in the neocortex of both NTLE and MTLE patients in similar concentrations. AA was found in the neocortex of one NTLE patient. These data support an association between NE depletion and NTLE. The relative NE deficiency along with the consistent presence of DA in NTLE patients suggest an impairment in the catecholamine pathway. The presence of AA, a co-factor in NE synthesis, in the neocortex of one NTLE patient may also be related since AA is a cofactor in NE synthesis.     

Tracer study on a paracellular route in experimental hydrocephalus

Summary Considering the possibility of a paracellular pathway for edema resoltuion, we studied the intracerebral movement of proteins and ionic lanthanum in rats with experimental hydrocephalus. Hydrocephalus was induced by injection of kaolin suspension into the cisterna magna. After induction of hydrocephalus, horseradish peroxidase (HRP), microperoxidase (MP), or lanthanum chloride (LaCl₃) were perfused into the ventricle system. HRP and MP were localized mainly in the intercellular spaces between ependymal cells, glial cells, and in perivascular spaces and were restricted by endothelial tight junctions. Ionic lanthanum (La³⁺), however, penetrated these tight junctions and moved between the blood and CSF cavities by paracellular pathways. These findings indicate that in obstructive hydrocephalus, the tight junctions may constitute part of a paracellular pathway for the transendothelial movement of small solutes, although they prevent the movement of larger molecules.     

Early ependymal changes in experimental hydrocephalus after mumps virus inoculation in hamsters

Summary To elucidate the pathogenesis of early ventricular dilatation in hydrocephalus, we examined early morphological changes in ependymal layers at the lateral ventricles in suckling hamsters without aqueductal stenosis 5 days after the intracerebral inoculation of mumps virus. Mumps virus antigen was detectable in all ependymal cells. The ependymal cilia had almost disappeared and only the microvilli remained. A number of supra-ependymal cells were also observed on the surface of the lateral ventricles. Transmission electron microscopy revealed intracytoplasmic viral-like inclusions in the infected ependymal cells. These results suggest that functional and morphological disturbances in infected ependymal cells may cause early ventricular dilatation before aqueductal stenosis occurs.Supported by a Grant-in-Aid from the Japanese Ministry of Health and Welfare for scientific research into intractable hydrocephalus,-and by a Grant-in-Aid for scientific research from the Ministry of Education, Japan (C.No. 02670435)     

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     

神经内镜下治疗交通性脑积水13例临床分析

目的 探讨神经内镜下行三脑室底造瘘术治疗交通性脑积水的可行性.方法 13例交通性脑积水病人术前、术后行NPHS、腰穿测ICP,对结果进行统计学处理.结果 本组11例有效,2例无效,无死亡病例.术后NPHS平均提高3.50,脑脊液压力平均下降40.44 mmH2O,差异有统计学意义(P<0.05).复查头颅MRI:9例脑...     

Management of hydrocephalus in ilio-omphalopagus conjoined twins

One member of ilio-omphalopagus conjoined twins developed symptomatic hydrocephalus. Uneventful ventriculoperitoneal shunting improved the baby's condition. Technical aspects of the neurosurgical and anesthetic management in this case are discussed.     

Consensus: modelling of hydrocephalus

Following a discussion of the principles behind the various animal models for hydrocephalus, work with past and more recently developed ones is presented.Presented at the Consensus Conference: Hydrocephalus '92, Assisi, Italy, 26–30 April 1992     

Monoamine neurotransmitters and amino acids in the cerebrum and striatum of immature rats with kaolin-induced hydrocephalus

Hydrocephalus is characterized by enlargement of the cerebral ventricles. The behavioral disturbances are, in some cases, rapidly reversible by surgical treatment suggesting that there may be a functional impairment of neurons. Hydrocephalus was induced in 3-week old rats by kaolin injection into the cisterna magna. Parietal cerebrum and striatum content of monoamine neurotransmitters and amino acids were assayed by high performance liquid chromatography (HPLC), 1, 2, or 4 weeks after induction of hydrocephalus. The ventricles exhibited progressive enlargement which was partially reversed by surgical treatment. Cerebral water content was increased at all stages. Increased levels of cerebral aspartate and glutamate suggest that there is the potential for excitatory neurotoxicity. The increase in cerebral taurine correlated negatively with the increase in water content. Cerebral concentrations of norepinephrine and serotonin, and its metabolite 5-HIAA, were increased at 1 and 2 weeks suggesting an increase in their turnover during the early stages of ventricular dilatation. Dopamine and its metabolite DOPAC were transiently diminished in the striatum at 1 and 2 weeks, respectively, suggesting that axonal projections from the brainstem may be impaired. We conclude that the effect of hydrocephalus on amino acids and monoamines varies regionally. Due to increased water content, there may be dilution effects in whole tissue, therefore, it is important to make determinations on the basis of protein content.     

Medullary monoamine levels during experimental tooth movement

We investigated possible influence of nociception induced by experimental tooth movement on the medullary monoaminergic inhibitory systems. Forty-eight hours after the start of the experimental tooth movement, significant increases in dorsal serotonin (5-HT), dopamine (DA), norepinephrine (NE), 5-hydroxyindoleacetic acid (5-HIAA), and dihydroxyphenylacetic acid (DOPAC) levels were detected with ipsilateral dominance. These results suggest that the nociception induced by experimental tooth movement might be under modulation of serotonergic, noradrenergic, and dopaminergic systems.     

The CSF myelin basic protein in pediatric hydrocephalus

Concentrations of myelin basic protein (MBP) in ventricular and lumbar cerebrospinal fluid (CSF) of 20 pediatric hydrocephalic patients were reviewed. Raised values were found to be particularly significant in children aged more than 1 year. Control measurements after shunt placement showed an important drop in the MBP concentration, which could therefore be considered a marker for correct functioning of the shunt. The dosage of MBP could play a role in assessing the activity of an hydrocephalic process. Preliminary data gained from monitoring of MBP in the lumbar CSF in posthemorrhagic neonatal hydrocephalus could yield further criteria for indication of a shunt operation.Presented at the Consensus Conference: Hydrocephalus '92, Assisi, Italy, 26–30 April 1992     

The ependyma in chronic hydrocephalus

H-Tx rats produce congenitally hydrocephalic offspring with varying severity of the condition. We used moderately hydrocephalic rats without evident clinical signs of hydrocephalus and normal controls from the same stock when they were at least 1.5 years old. Macroscopic anatomy was studied by MRI and in fixed brain slices and the ultrastructure of the ependyma, with REM. Apart from markedly stretched areas, where the ependyma was totally destroyed and subependymal structures directly exposed to the CSF, the density of ependymal microvilli and of tufts of cilia was reduced in proportion to the ventricular distension of a given area. A supraependymal “network”– never seen before in acute hydrocephalus – was found, whose purpose is probably to prevent further ventricular enlargement. We conclude that even in arrested hydrocephalus the ependymal sequelae of hydrocephalus are similar to those of the acute stage, illustrating the extremely limited potenctial for recovery, but the organism seems nevertheless to react with an internal stabilization of the ventricular system. Received: 8 January 1998