Periodic oscillation of intracranial pressure in ventricular dilation: a preliminary report

Artificial pressure waves (PWs) were generated by manual inflation of a balloon in the trigonum of the lateral ventricle in seven adult mongrel dogs with normal cerebrospinal fluid (CSF) circulation. In 14 of 16 series of continuous appearances of artificial PWs, local shifts of the brain were successfully monitored using small strain-gauge sensors at the periventricular structures in these animals. Of the 14 series, 13 showed displacements of the periventricular structures, suggesting ventricular dilation. These results did not always correlate with macroscopic findjngs. They are thought to be due largely to periventricular oedemas and, in part, non-uniform dilations of the ventricles during PWs. We conclude that a water hammer formed by reflection of an increased pulse pressure of PWs at the site of CSF absorption causes a shift of CSF from the ventricle to the periventricular structures through the wall of the ventricle. This phenomenon appears amplified in patients with impaired CSF absorption. Thus, PWs have a pathological role in the progress of ventricular dilation in patients with normal pressure hydrocephalus.     

The relationship of intracranial venous pressure to hydrocephalus

Little is known about intracranial venous pressure in hydrocephalus. Recently, we reported that naturally occurring hydrocephalus in Beagle dogs was associated with an elevation in cortical venous pressure. We proposed that the normal pathway for cerebrospinal fluid (CSF) absorption includes transcapillary or transvenular absorption of CSF from the interstitial space and that the increase in cortical venous pressure is an initial event resulting in decreased absorption and subsequent hydrocephalus. Further analysis, however, suggests that increased cortical venous pressure reflects the effect of the failure of transvillus absorption with increase in CSF pressure on the venous pressure gradient between ventricle and cortex. Normally, the cortical venous pressure is maintained above CSF pressure by the Starling resistor effect of the lateral lacunae. A similar mechanism is absent in the deep venous system, and thus the pressure in the deep veins is similar to that in the dural sinuses. Decreased CSF absorption causes an increase in CSF pressure followed by an increase in cortical venous pressure without a similar increase in periventricular venous pressure. The periventricular CSF to venous (transparenchymal) pressure (TPP) gradient increases. In contrast, cortical vein pressure remains greater than CSF pressure (negative TPP). The elevated periventricular TPP gradient causes ventricular dilatation and decreased periventricular cerebral blood flow (CBF), a condition that persists even if the CSF pressure returns to normal, particularly if tissue elastance is lessened by tissue damage. If deep CBF is to be maintained, periventricular venous pressure must increase. Since the veins are in a continuum, cortical venous pressure will further increase above the CSF pressure. Understanding these principles related to intracranial venous pressure helps in the selection of shunt characteristics that best match the pathologic condition.Presented at the Consensus Conference: Hydrocephalus '92, Assisi, Italy, 26–30 April 1992     

放射性核素脑池造影对正常颅压性脑积水诊治的价值研究

目的探讨放射性核素脑池造影对正常颅压性脑积水术前诊断准确性的影响及对预测分流术疗效的价值。方法 2013年1月起至2015年1月期间,三六三医院神经外科收治的患者头颅MRI扫描显示脑室系统扩张符合脑积水形态学特征,并排除梗阻因素,入院初步考虑"交通性脑积水",入院后常规行放射性核素脑池造影。结果 65名脑室系统扩张的患者行放射性核素脑池造影,其中12名患者在动态扫描后发现放射性核素脑室内未显像,且吸收正常,结合症状排除脑积水诊断,仅考虑为脑室系统扩张而非脑积水;另53名患者发现放射性核素脑室内返流伴有核素明显延迟吸收,确诊为脑脊液吸收功能障碍,结合颅内压的测定及Tap试验,符合正常颅压性脑积水诊断,其中47名行分流术,术后6个月后其步态、认知及尿失禁等症状显著改善。结论头颅MRI常规扫描虽能明确大部分脑积水诊断,但对于脑萎缩后脑室系统扩张以及正常颅压性脑积水患者,若不能明确脑脊液在脑室系统中的循环及吸收情况,往往会造成误诊,放射性核素脑池造影可作为一种辅助手段应用于正常颅压性脑积水患者的术前疗效评估中。     

On the pathology of experimental hydrocephalus induced by artificial increase in endoventricular CSF pulse pressure.

In lambs, acute and chronic communicating hydrocephalus has been created by merely increasing the amplitude of the intraventricular cerebrospinal fluid (CSF) pulsations, leaving the mean CSF pressure unchanged. The pathologic changes occurring in this type of hydrocephalus do not differ qualitatively from those observed in obstructive hydrocephalus. Beside demonstrating a direct role of ventricular pulsations in the ventricular dilation, the observed findings indicate that an increase in mean CSF pressure is not a necessary condition for the occurrence of the hydrocephalus. Consequently, the hypothesis of abnormal high intraventricular CSF pressure oscillations at the basis of the ventricular dilation of normal pressure hydrocephalic patients, receives a significant support. Further support is provided is provided by considering the recorded experimental pathological lesions are quite similar to those observed in normal pressure hydrocephalic patients with patent subarachnoid CSF pathways.     

Communicating hydrocephalus induced by mechanically increased amplitude of the intraventricular cerebrospinal fluid pressure: experimental studies

Acute and chronic hydrocephalus was induced in lambs by mechanically increasing the amplitude of the cerebrospinal fluid (CSF) intraventricular pulse pressure without modifying the mean CSF pressure and without interfering with CSF circulation or absorption. The characteristics of the hydrocephalus so obtained, namely, the asymmetry of ventricular dilation, the dilation of the distal portions of the ventricular system, and the absence of obstructions in CSF pathways, indicated a direct role of high-amplitude intraventricular CSF pulsations in the genesis of ventricular enlargement. As no impairment in CSF circulation or absorption was induced nor variations in CSF mean pressure, this experimental model is proposed as a model for communicating hydrocephalus.     

The effect of increased CSF pressure on interstitial fluid flow during ventriculocisternal perfusion in the cat

Transependymal absorption of cerebrospinal fluid (CSF) in hydrocephalus is suggested by periventricular edema, but the necessary bulk flow of interstitial fluid (ISF) has not been found. We performed ventriculocisternal perfusions in adult cats using CSF with the extracellular marker [³H]sucrose. CSF pressure was maintained at — 5 (control), 20 or 40 cm H₂O for 2 or 4 h. Some animals had perfusions with isotope for the full experiment while others had an isotope-free perfusion for 2 h followed by a delayed-pulse with isotope. Apparent diffusion coefficients and distribution spaces for sucrose were determined from depth of isotope penetration. White matter apparent diffusion coefficients were statistically increased compared to controls for the 4-h 20 cm H₂O and 2-h 40 cm H₂O experiments. Apparent diffusion coefficients for delayed-pulse experiments at increased pressure were greater than those of full-pulse. Sucrose distribution spaces were not enlarged at the various pressures. Alteration of ISF transport in periventricular white matter occurred with increased pressure. These time-dependent changes in bulk flow rate indicate either a decrease in normal ISF flow toward the ventricle or reversal of transependymal ISF flow.     

Idiopathic normal pressure hydrocephalus: the CSF tap-test may predict the clinical response to shunting

A follow-up study was performed in nine patients with idiopathic normal pressure hydrocephalus (NPH) 37 months (mean) after shunting and 10 non-operated controls with comparable degrees of ventricular enlargement, gait disorder, and dementia. Five operated patients vs. no controls reported sustained general improvement (p<0.02). Objectively improved gait at follow-up (compared with preoperative status) was found in five of the six tested NPH-patients vs. none of the controls (p< 0.005). Improved gait and/or psychometric function was found in four of six NPH vs. none of eight control patients (p<0.02) after drainage of 40 ml cerebrospinal fluid (CSF tap-test). Improved gait during the CSF tap-test predicted continued improvement at follow-up. Temporal horn size was the only radiological variable which showed a (moderate) positive correlation with resistance to CSF absorption and rate of pressure increase. The size of the third ventricle diminished in parallell with clinical improvement.     

Paradigm shift in hydrocephalus research in legacy of Dandy’s pioneering work: rationale for third ventriculostomy in communicating hydrocephalus

Objective This study aims to question the generally accepted cerebrospinal fluid (CSF) bulk flow theory suggesting that the CSF is exclusively absorbed by the arachnoid villi and that the cause of hydrocephalus is a CSF absorption deficit. In addition, this study aims to briefly describe the new hydrodynamic concept of hydrocephalus and the rationale for endoscopic third ventriculostomy (ETV) in communicating hydrocephalus. Critique The bulk flow theory has proven incapable of explaining the pivotal mechanisms behind communicating hydrocephalus. Thus, the theory is unable to explain why the ventricles enlarge, why the CSF pressure remains normal and why some patients improve after ETV. Hydrodynamic concept of hydrocephalus Communicating hydrocephalus is caused by decreased intracranial compliance increasing the systolic pressure transmission into the brain parenchyma. The increased systolic pressure in the brain distends the brain towards the skull and simultaneously compresses the periventricular region of the brain against the ventricles. The final result is the predominant enlargement of the ventricles and narrowing of the subarachnoid space. The ETV reduces the increased systolic pressure in the brain simply by venting ventricular CSF through the stoma. The patent aqueduct in communicating hydrocephalus is too narrow to vent the CSF sufficiently.     

Ventricular cerebrospinal fluid neurofilament protein levels decrease in parallel with white matter pathology after shunt surgery in normal pressure hydrocephalus

Normal pressure hydrocephalus (NPH) is characterized by disturbed cerebrospinal fluid (CSF) dynamics and white matter lesions (WML). Although the morphology of these lesions is described, little is known about the biochemistry. Our aim was to explore the relationship between ventricular CSF markers, periventricular WML and postoperative clinical outcome in patients with NPH. We analysed lumbar and ventricular concentrations of 10 CSF markers, 12 clinical symptoms and signs, magnetic resonance imaging (MRI) periventricular white matter hyperintensities (PVH) and ventricular size before and 3 months after shunt surgery in 35 patients with NPH. Higher ventricular CSF neurofilament protein (NFL), an axonal marker, correlated with more extensive PVH. A larger postoperative reduction in NFL correlated with larger reduction in PVH and a more pronounced overall improvement. Albumin ratio, HMPG, NPY, VIP and GD3 increased postoperatively whereas NFL, tau and HVA decreased. Variations in ventricular size were not associated with CSF concentrations of any marker. We conclude that NPH is characterized by an ongoing periventricular neuronal dysfunction seen on MRI as PVH. Clinical improvement after shunt surgery is associated with CSF changes indicating a restitution of axonal function. Other biochemical effects of shunting may include increased monoaminergic and peptidergic neurotransmission, breakdown of blood brain barrier function, and gliosis.     

Pressure wave with apnoea evaluated by sleep level in patient with ventricular dilation

Seventeen patients who were suspected of having hydrocephalus, because of ventricular dilation from various causes, were included in this study of the pathophysiologic basis of the appearance of pressure waves (PWs). Pressure waves accompanied by apnoeas originated in arousal responses in the resting state of these patients. Frequent fits of apnoea were included in the entire sleep apnoea syndrome. Most pressure waves characteristically appeared in the state of non-REM sleep. During the appearance of such pressure oscillations, intracranial pressure was elevated transiently. This coincidence in the appearance of pressure oscillations with sleep apnoea was the most characteristic pathophysiologic result from this polygraphic study of the patients.     

Accelerated progression of kaolin-induced hydrocephalus in aquaporin-4-deficient mice.

Hydrocephalus is caused by an imbalance in cerebrospinal fluid (CSF) production and absorption, resulting in excess ventricular fluid accumulation and neurologic impairment. Current therapy for hydrocephalus involves surgical diversion of excess ventricular fluid. The water-transporting protein aquaporin-4 (AQP4) is expressed at the brain-CSF and blood-brain barriers. Here, we provide evidence for AQP4-facilitated CSF absorption in hydrocephalus by a transparenchymal pathway into the cerebral vasculature. A mouse model of obstructive hydrocephalus was created by injecting kaolin (2.5 mg/mouse) into the cisterna magna. Intracranial pressure (ICP) was approximately 5 mm Hg and ventricular size <0.3 mm(3) in control mice. Lateral ventricle volume increased to 3.7+/-0.5 and 5.1+/-0.5 mm(3) in AQP4 null mice at 3 and 5 days after injection, respectively, significantly greater than 2.6+/-0.3 and 3.5+/-0.5 mm(3) in wildtype mice (P<0.005). The corresponding ICP was 22+/-2 mm Hg at 3 days in AQP4 null mice, significantly greater than 14+/-1 mm Hg in wildtype mice (P<0.005). Brain parenchymal water content increased by 2% to 3% by 3 days, corresponding to approximately 50 muL of fluid, indicating backflow of CSF from the ventricle into the parenchymal extracellular space. A multi-compartment model of hydrocephalus based on experimental data from wildtype mice accurately reproduced the greater severity of hydrocephalus in AQP4 null mice, and predicted a much reduced severity if AQP4 expression/function were increased. Our results indicate a significant role for AQP4-mediated transparenchymal CSF absorption in hydrocephalus and provide a rational basis for evaluation of AQP4 induction as a nonsurgical therapy for hydrocephalus.     

梗阻性脑积水侧脑室及室周脑组织生物力学响应的有限元分析

目的运用有限元方法对梗阻性脑积水进行计算机模拟,研究分析侧脑室及室周脑组织的生物力学响应及其所产生的病理生理影响。方法依据正常国人颅脑MRI轴位T2加权图像获取解剖信息,在有限元软件ANSYS中生成包含侧脑室前、后角和体部的半侧脑层面的二维有限元模型。模拟脑组织为固、液两相物质组成的线性多孔弹性材料,设定生物力学特性参数及边界条件和初始条件,施加载荷,运用有限元软件ABAQUS进行计算求解,以云图形式输出结果。结果有限元模型动态模拟了梗阻性脑积水侧脑室各部的扩张过程,直观显示出各个时间步室周脑组织内的应力类型及分布、各部的应变和位移。结论膨胀性应力集中引起角部脑水肿;梗阻性脑积水早期侧脑室角部形态变化最明显;体部附近脑组织结构容易受压移位。这些生物力学响应是室内压增高的结果,也与侧脑室的解剖形态密切相关。     

Monoamine acid metabolites and cerebrospinal fluid dynamics in normal pressure hydrocephalus: preliminary results.

Lumbar and ventricular CSF concentration of homovanillic acid (HVA) and 5-hydroxy-indole-acetic acid (5-HIAA) have been determined in 13 patients admitted to hospital for suspected normal pressure hydrocephalus. Low values of HVA in lumbar CSF were found in all patients with reduced CSF absorption and CSF flow inversion. The HVA lumbar concentration remained low after shunt procedure; it increased if obstruction of the shunt occurred. The ventricular CSF concentration of HVA was normal before surgery; it became higher, in two cases, after surgery. No important variations were found in the lumbar and ventricular CSF concentration of 5-HIAA. The possible mechanisms and diagnostic value of these findings are discussed.     

Cerebrospinal fluid absorption mechanism--based on measurement of CSF flow rate in shunt tube

The cerebrospinal fluid (CSF) absorption mechanism in cases of hydrocephalus was investigated on the basis of measurements of CSF flow in a shunt tube after ventriculo-peritoneal shunt surgery, monitoring of intracranial pressure, CT findings, radioisotope cisternography, cerebral blood flow, EEG, PSP tests and changes in neurological findings. The subjects were 6 males and 7 females aged from 18 to 70. CSF flow rates in the shunt tubes were between 0.01 and 1.93 ml/min. Calculating the daily volume of CSF flow, the subjects were divided into two groups: Group A (8 patients) with a volume of less than 150 ml/day (0.01-0.25 ml/min), and Group B (5 patients) with between 150 and 500 ml/day (0.01-1.93 ml/min). Monitoring of intracranial pressure prior to the shunt operation was performed in 10 cases. These pressure values ranged between 4 and 25 mmHg (mean: 7-8 mmHg), and there was no difference between the two groups. The pre-and post-operative radioisotope cisternography findings indicated improvement of ventricular dilatation, periventricular lucency and ventricular reflux. After the shunt operations, there was neurological improvement in 6 of the 8 Group A cases but only in 2 of the 5 Group B cases. Considering the CSF flow volumes of the two groups, it appears that in Group A the shunt tube is not the main CSF circulation pathway. This could mean that resistance to CSF absorption in the cerebrospinal space has decreased after the shunt operation and there has been recovery of the physiological CSF absorption pathways. In other words, neurological improvement can be expected in this group A.     

Prognostic significance of third ventricle dilation in spontaneous intracerebral hemorrhage: a preliminary clinical study

OBJECTIVE: Although numerous factors have been described that predict outcome after spontaneous intracerebral hemorrhage (ICH), very little is know about the role of hemorrhagic dilation of the third ventricle in development of hydrocephalus and prognosis. The objective of this study was to investigate whether the presence of hemorrhagic third ventricle dilation after ICH would predict development of hydrocephalus and outcome. METHODS: We identified the patients with spontaneous ICH treated with external ventricular drainage (EVD) in this retrospective study. Computerized tomography (CT) was performed at admission within 24 hours of onset and retrospectively analysed to determine lesion size and location, status of third and fourth ventricle and frontal horn index (FHI). Glasgow coma scale (GCS) score, mean arterial pressure (MAP), etiology and demographic data were obtained from medical records. Outcome was determined using modified Rankin score at month 3. Patients with and without third ventricle dilation were compared in terms of hydrocephalus (FHI > 0.38), initial GCS score, age and MAP, and analyses were performed to determine whether third ventricle dilation was a predictor of poor outcome. RESULTS: Of the 22 patients studied, all had thalamic or basal ganglia hemorrhage with intraventricular hemorrhage (IVH) and all are treated with external ventricular drainage (EVD). Of the 22 patients, 12 had third ventricle dilation (width > or = 10 mm) and ten patients had non-dilated third ventricle (width < 10 mm). Patients with third ventricle dilation had lower GCS scores (7.4 +/- 1.8 versus 9.7 +/- 2.1, p < 0.005) and had higher FHI (0.46 +/- 0.06 versus 0.38 +/- 0.02, p < 0.005) as compared to patients with non-dilated third ventricle. The differences in age (59.5 +/- 9.4 versus 59.2 +/- 11.2) and MAP (128.3 +/- 16.0 versus 130.5 +/- 13.6) of the patients were not significant statistically. Sixty-six percent of patients (8/12) with third ventricle dilation and 60% of patients (6/10) with normal third ventricle were dead 6 months post-operation and mortality rate did not differ significantly. DISCUSSION: Although the roles of various factors are well described in the prognosis of spontaneous ICH, little is known about the role of third ventricle dilation. Based on our results, we concluded that third ventricle dilation is a poor prognostic factor.     

Significance of diffusion-weighted imaging and apparent diffusion coefficient maps for the evaluation of pyogenic ventriculitis

OBJECTIVE: The aim of this study is to assess the significance of an apparent diffusion coefficient (ADC) modality for the diagnosis and follow-up evaluation of ventriculitis. PATIENTS AND METHODS: Twelve patients with ventriculitis were enrolled in this study. Diffusion-weighted (DW) magnetic resonance images (MRI) and ADC maps of the periventricular white matter, intraventricular collections detected in the third or lateral ventricles and normal cerebrospinal fluid (CSF) were obtained. The images and ADC data from each lesion were correlated and then compared amongst the different lesions. CSF studies were performed via external ventricular drain (EVD) catheters or lumbar punctures performed on the same day as ADC mapping. Linear regression was used to analyze relationships among pleocytosis, glucose, chloride, protein content of pus, and ADC counting. RESULTS: A total of 24 ADC values for intraventricular pus and CSF findings were obtained from 12 patients and analyzed. The DW MRI showed marked hyperintensity in purulent lesions, and the corresponding ADC maps revealed prominent hypointensity and decreased ADC values in dependent CSF compared with non-dependent CSF and normal white matter. Dependent CSF is defined as the CSF which is mixed with purulent discharge which is located at the lower portion of the ventricle by gravity. The correlations between ADC counting and pleocytosis, and also protein content were strong: r(2)=-0.84, r(2)=-0.62, respectively (p<0.001). CONCLUSION: A decreased ADC value and increased signal intensity of dependent intraventricular fluid by DW MRI suggests the presence of material with restricted water diffusion in the ventricular space. This is seen in pyogenic ventriculitis when water diffusion is restricted in suppurative fluid. ADC counting is negatively correlated with pleocytosis and the protein content of CSF. Therefore, the ADC value might be a useful non-invasive method for the follow-up evaluation of ventriculitis as well as the diagnosis of it.     

Posthemorrhagic ventricular dilation in the neonate: development and characterization of a rat model

Intraventricular hemorrhage is a common complication of prematurity. Posthemorrhagic ventricular dilation (PHVD) has a high rate of disability and no safe and effective treatment. Its pathogenesis is poorly understood, largely because of the lack of a satisfactory animal model. We have developed a model of neonatal PHVD in the rat. Seven-day-old (P7) Wistar rat pups were given 80-microl injections of citrated rat blood or artificial cerebrospinal fluid (CSF) into alternate lateral ventricles on P7 and P8. Intracranial pressure was monitored and increased briefly by over 8-fold. Some rats received further 10-microl intraventricular injections of India ink on P21. Animals were weighed daily and simple neurologic tests performed. On P21 (or P22 if India ink had been injected), the rats were perfusion-fixed and blocks processed for paraffin histology. Sixty-five percent of pups injected with blood and 50% injected with artificial CSF developed dilated lateral ventricles, with patchy loss of ependyma, marked astrocytic gliosis, and rarefaction of periventricular white matter. India ink injection revealed slow transit of CSF from the dilated lateral ventricles but eventual passage into the subarachnoid space. Pups that had received intraventricular injections but did not develop ventricular dilation nonetheless had lighter brains than littermate controls (p < 0.001). Body weights were not significantly different from controls. Hydrocephalic animals had reduced motor performance as assessed by a grip traction test (p = 0.0002). This model is well suited to studying the pathogenesis of PHVD.     

脑室镜三脑室造瘘术治疗小儿阻塞性脑积水

目的分析本组49例病例，就手术病种和年龄的选择、手术方法及技巧做一介绍。方法全组49例，年龄1个月-18岁，平均33个月。CT、MRI及^99Tc^m-DTPA证实为脑脊液吸收功能正常的阻塞性脑积水。手术方法为经侧脑室、室间孔、三脑室置入神经内镜，于三脑室底与脚间池造一瘘孔。结果术后随访半年-5年，39例有好转；10例因无改善于术后3个月再行脑室腹腔分流手术，术后脑脊液漏3例，未有出血、感染及神经功能损伤等并发症。结论脑室镜三脑室底脚间池造瘘适用于脑脊液吸收功能正常的阻塞性脑积水。脑脊液吸收功能判断需靠同位^99Tc^m-DTPA检查。继发性脑积水治疗效果好于原发性脑积水，大龄儿童效果好于婴幼儿。     

Cerebrospinal fluid pressure and resistance to absorption during development in normal and hydrocephalic mutant mice

Hydrocephalic mutant mice and matched siblings at different ages were used to measure the pressure and the resistance to drainage of the cerebrospinal fluid (CSF) from the lateral ventricles and from the cisterna magna with glass micropipets. The resting CSF pressure in normal mice increased between 1 to 2 and 4 to 8 days after birth and subsequently decreased between 4 to 8 and 14 days after birth. In hydrocephalic mice the resting pressure was not significantly different from normal in the 1st week after birth, but by 14 days the pressure was significantly higher in hydrocephalic mice. For normal mice, the resistance from the lateral ventricles at 1 to 2 days after birth was 143.9 mm H2O min microliter-1 and it decreased rapidly to 62.0 at 4 to 8 days, and to 21.2 mm H2O min microliter-1 at 14 days. The resistance to absorption from the cisterna magna in normal mice declined from 94.9 to 44.4 and to 26.8 mm H2O min microliter-1 at 1 to 2 days, 4 to 8 days, and 14 days after birth, respectively, suggesting that the absorptive capacity of the subarachnoid outflow sites increased during that period. Thus resistance measured from the lateral ventricles was significantly higher than that from the cisterna magna in the 1st week after birth, suggesting that in immature mice there is a resistance to flow of CSF through the ventricular system. In hydrocephalic mice the resistance measured from the lateral ventricles was higher than for normal animals at 181.5, 106.4, and 103.7 mm H2O min microliter-1 for 1 to 2 days, 4 to 8 days, and 14 days, respectively. Resistance from the cisterna magna in hydrocephalic animals was not significantly different from normal at any age. Thus it is concluded that the hydrocephalus is associated with an obstruction to the flow of CSF from the ventricles.     

The effect of subfornical organ lesions and ventricular blockade on drinking induced by angiotensin II.

The role of the subfornical organ (SFO) as the unique receptor site for the drinking behavior induced by intracranial injections of angiotensin II (AII) was investigated. It was found that: (1) drinking in response to intraventricular (IVT) injections of AII was reduced in 6 rats but was unchanged after 80-100% damage of the SFO in 4 cases; (2) reduction of drinking to lateral ventricular application of AII was seen with no apparent SFO damage in 4 rats; (3) recovery of the AII induced drinking deficit was consistently observed within a short time interval (14 days), even in those animals with complete SFO lesions: (4) the presence of ventricular debris was correlated with deficits in water intake to IVT angiotensin injections. In a second experiment artificial blockade of the ventricular space was produced by a plugging technique. Plugging the anterior third ventricle simulated the effects of SFO lesioning. It was concluded that the SFO is not a unique receptor area since the ventral anterior third ventricle is also sensitive for AII (IVT) induced drinking. If the SFO is a receptor site for AII circulating in the CSF it is probably not the only periventricular receptor site. Access of AII to the anterior ventral third ventricle appears to be essential for inducement of drinking.