Angiotensin II receptor content within the subfornical organ and organum vasculosum lamina terminalis increases after experimental subarachnoid haemorrhage in rats

Summary Nests of cells within the central nervous system, namely the circumventricular organs (CVOs) which include the subfornical organ (SFO), organum vasculosum lamina terminalis (OVLT), area postrema (AP) and the median eminence (ME) are known to contain not only receptors for angiotensin II (ANG II) but also ANG II itself. Though the significance of this central ANG II network in the pathophysiology of certain conditions like hypertension is well established, there appears to be a lack of knowledge as to how this system might be involved after subarachnoid haemorrhage (SAH). In this study, we have investigated ANG II receptor content change at various circumventricular organs after experimental subarachnoid haemorrhage in rats using a transcervical transclivai model. ANG II receptor content was detected by in vivo autoradiography using intracisternal ANG II Sar 1, Ile 8 labelled with iodine (I) 125 both at 30 minutes and 48 hours after the SAH. Serum angiotensin converting enzyme activity was also detected during the time course reflecting the involvement of the peripheral angiotensin system and showed an early rise and a fall after two days. Immunohistochemistry was utilized to show the ANG II-containing cells within the circumventricular organs. SFO and OVLT were found to have a statistically significant increase in ANG II receptor content persisting over two days after the SAH. These alterations in the receptor content of CVOs may indicate their possible role in delayed ischaemic deficits seen after SAH.     

Foregut smooth muscle reactivity changes in the hydrocephalus-induced infantile rats

BACKGROUND: An association between hydrocephalus and gastroesophageal motor abnormalities that cause gastroesophageal reflux (GER) is well known. Our aim was to investigate hydrocephalus-induced alterations in esophageal and gastric smooth muscle reactivity and their modulation by pharmacological interventions in the rat model. MATERIALS AND METHODS: Hydrocephalus was induced in infantile rats by injection of kaolin into the cisterna magna. Hydrocephalic and sham-operated rats were exsanguinated 2 weeks after surgery. Esophageal and gastric fundus smooth muscle strips were studied in vitro for their contractile and relaxant response to receptor activation in the organ chambers set up. Additionally, esophageal and gastric tissue specimens were examined histologically for GER-induced changes. RESULTS: No histological evidence of esophageal and gastric changes reflecting GER was observed in the specimens of the control and hydrocephalus-induced rats. Maximum contractile responses of esophageal and gastric fundus smooth muscle to KCl and muscarinic receptor agonist carbachol were increased in the hydrocephalic groups compared with the control groups. These changes were statistically significant. Relaxant responses to beta adrenoceptor agonist isoprenaline were similar in the esophageal muscle strips of both hydrocephalic groups and the control groups. However, isoprenaline-induced relaxant responses of the gastric fundus muscle strips in the hydrocephalus-induced groups were significantly decreased as compared with the control groups. The relaxant responses to papaverine in the esophageal and gastric fundus smooth muscle strips were similar in the two groups. CONCLUSIONS: Our study revealed alterations of receptor-dependent and receptor-independent foregut smooth muscle reactivity in the hydrocephalus-induced rat pups. Therefore, we suggest that impaired smooth muscle reactivity at least in part may contribute to abnormalities of foregut motor function seen in patients with hydrocephalus.     

Sinusoidal Intrathecal Infusion for Assessment of CSF Dynamics in Kaolin-Induced Hydrocephalus

Summary Objective. To evaluate whether changes of CSF outflow resistance and compliance in hydrocephalus can be assessed by an intrathecal infusion which is performed at a sinusoidal varying rate. Methods. Hydrocephalus was produced in 10 Sprague Dawley rats by instillation of 0.0375 g of kaolin in 0.9% saline into the cisterna magna. Measurements were performed 4 weeks later: With each animal both, three successive constant rate infusions (0–0.02 ml/min) and a sinusoidal infusion (0–0.02 ml/min, frequency 0.006 Hz) were performed. 6 normal animals served as control. The pressure recordings of both infusion techniques were used for the assessment of the CSF outflow resistance. The time constant and the pressure volume index were calculated only from the sinusoidal input testing. Results. The sinusoidal test as well as the constant rate infusion both demonstrated a severe impairment of CSF absorption. By the sinusoidal input, a decreased compliance was confirmed additionally. Thus, the sinusoidal infusion test demonstrated a high resistance and low compliance hydrocephalus in the kaolin-treated group. A simple graphical procedure is presented which allows an easy assessment of CSF dynamics by the sinusoidal infusion test.     

Kaolin-induced congenital hydrocephalus in utero in fetal lambs and rhesus monkeys

A model of congenital hydrocephalus in utero in fetal lambs and rhesus monkeys has been produced by the intracisternal injection of kaolin. Initial attempts to produce hydrocephalus using silicone oil were unrewarding. Hydrocephalus had developed by 2 weeks post-injection and could be followed by ultrasonography. The pathological findings were similar to those reported using kaolin in other species. Ventriculoamniotic shunting, when successful, was capable of partially reversing the deleterious effects of hydrocephalus. The major drawback of the present model is that hydrocephalus is produced during the second rather than the first trimester of pregnancy. However, kaolin produces mainly an obstructive hydrocephalus without other associated brain or systemic anomalies.     

Changes in the components and content of biological water in the brain of experimental hydrocephalic rabbits

Changes in biological water components and their respective content in the cortical gray matter and periventricular white matter were studied in rabbits rendered hydrocephalic by intracisternal kaolin injection. There was no change in either total water content or free or bound water content in the cortical gray matter at the various stages of hydrocephalus development. While there was no significant change in total water content in the periventricular white matter at any stage of hydrocephalus, free water content was significantly elevated and bound water content was decreased at the acute and subacute stages, with a return to relatively normal levels at the chronic stage. It is concluded that in the periventricular white matter, free water enters the brain across the ependymal lining during the acute and subacute stages of experimental hydrocephalus with a simultaneous reduction in the bound water and that there is some recovery at the chronic stage. It is suggested that alternative drainage pathways may develop in chronic hydrocephalus allowing drainage of free water in the periventricular white matter, which in turn permits bound water to return to relatively normal levels.     

Access-Port Fixation on the Left Pectoral Fascia in Laparoscopic Adjustable Gastric Banding

Access-port (AP) complications after laparoscopic adjustable gastric banding (LAGB) are often seen but seldom reported in literature. AP complications requiring additional surgery is reported in 3.6% to 24% of LAGB patients (Susmallian et al. Obes. Surg, 4:128–131, 2003; Peterli et al. Obes. Surg., 12(6):851–856, 2002; Busetto et al. Obes. Surg., 12:83–92, 2002; Mittermair et al. Obes. Surg., 19:446–450, 2009; Holeczy et al. Obes. Surg., 9:453–455, 1999; Bueter et al. Arch. Surg., 393:199–205, 2008; Launay-Savary et al. Obes Surg, 18:1406–1410, 2008; Balsiger et al. J. Gastrointest. Surg., 11:1470–1477, 2007; Szold and Abu-Abeid Surg. Endosc., 16:230–233, 2002). We evaluated the effect of fixing the AP on the pectoral fascia using the Velocity™ Injection Port on complication and re-operation rate. From January 2005 till October 2007, 619 LAGB procedures were performed using the SAGB QuickClose™. All procedures were performed by three dedicated surgeons using the pars flaccida technique. APs were placed on the fascia of the pectoral muscle using an infra-mammary incision. The AP device was fixed on the fascia using the Velocity™ Injection Port and Applier. Data was obtained retrospectively and records of 619 consecutive patients were reviewed for access-port complications. Sixty-eight AP complications were observed. Complications could be divided in four categories. Discomfort was reported in 30 patients, seven needing additional surgery. Infection contributed to 11 patients needing surgical removal of the device. Fourteen Patients with superficial infection were treated conservatively. Nine patients had inaccessible APs. Ultrasound-guided access was required in three patients. The remainder needed surgical relocation of the AP. Leakage of the tube was observed in four patients all of which needed revisional surgery. Our experience shows that fixation of the AP on the left pectoral fascia using the Velocity™ leads to a readily accessible AP with good anaesthetic and aesthetic results. In our series, 68 (11%) complications were recorded, of which 28 (4.5%) needed additional surgery.     

Cerebral blood flow alterations in progressive communicating hydrocephalus: transcranial Doppler ultrasonography assessment in an experimental model

OBJECT: In many cases communicating hydrocephalus is the result of impairments in cerebrospinal fluid absorption in the arachnoid villi at the cranial convexity. Reported methods of creating experimental hydrocephalus have not sought to produce an arachnoidal adhesion in the cranial convexity. In this study the authors investigate alterations in cerebral blood flow (CBF) in experimental communicating hydrocephalus induced by the injection of kaolin into the subarachnoid space at the convexity in neonatal rats. METHODS: In neonatal rats, kaolin was injected into the subarachnoid space at the cranial convexity. Assessment of CBF alterations was performed using transcranial Doppler ultrasonography preinjection and at 10 days, 4 weeks, and 8 weeks postinjection. Light microscopy examination was also performed at 4 weeks and 8 weeks postinjection. Conspicuous lateral ventricle enlargements of different dimensions were observed in kaolin-injected rats at 4 to 8 weeks postinjection. The third and fourth ventricles were dilated to a lesser extent. Resistance to CBF and increased mean CBF velocity were apparent 8 weeks after kaolin injection. Further, destruction and even loss of ependymal layers were more prominent at the chronic stage. CONCLUSIONS: The present model may be considered a progressive communicating hydrocephalus because of marked changes in blood flow dynamics and destruction of the ependymal layer at the chronic stage.     

Progression of experimental infantile hydrocephalus and effects of ventriculoperitoneal shunts: an analysis correlating magnetic resonance imaging with gross morphology

Although previous ultrasonographic studies did monitor ventricular enlargement successfully in experimentally-induced models of feline hydrocephalus, the resolution of neuroanatomic detail was relatively poor after placement of a ventriculoperitoneal (VP) shunt because the skull had ossified over the coronal sutures. Therefore, the present study employed magnetic resonance imaging to follow the progression of ventriculomegaly more accurately, as well as to evaluate the compensatory effects of VP shunting. Hydrocephalus was induced in kittens between 7 and 10 days old by injection of kaolin into the cisterna magna. Age-matched controls received similar injections of saline. At 9 to 14 days after the kaolin injection, the hydrocephalic animals received VP shunts. Anesthetized kittens were scanned at various intervals before and after shunt placement and were killed for morphological correlation. The features observed on the magnetic resonance imaging scans were consistent with the gross morphological changes that accompanied ventricular enlargement. The lateral ventricle began to enlarge as early as 1 day after the kaolin injection, and within 3 days, both the occipital and temporal horns, along with the 4th ventricle, showed signs of moderate dilatation. By 5 days, a bilateral communication had been established through the septum pellucidum. Continued expansion of the ventricular system occurred from 6 to 20 days after injection, to the point where the cerebral cortex was reduced to less than 25% of its original thickness. The internal capsule was stretched and edematous, the caudate nucleus was compressed ventrolaterally, and the cerebellar hemispheres were eroded and/or compressed. Animals in which shunts were successfully placed demonstrated a dramatic improvement in behavior, and a reduction of about 50% in the size of the lateral ventricles within 2 days. In some cases, the lateral ventricles became slit-like within 1 week. When they were killed, about half of the animals that received shunts exhibited mild to moderate ventriculomegaly. These results indicate that magnetic resonance imaging is an excellent method for visualizing the morphological changes associated with this animal model, that these alterations occur soon after the onset of hydrocephalus, and that VP shunting can successfully reduce ventriculomegaly.     

Alterations in the mechanical properties of bladder smooth muscle in hydrocephalus rat model

Objectives

It is now well established that hydrocephalus is associated with impaired bladder function. The aim of this study was to determine the effects of hydrocephalus on bladder smooth muscle (BSM) reactivity in the rat model.

Materials and Methods

Hydrocephalus was induced in 7-day-old rats by injection of kaolin into the cisterna magna (AH group). Control group rats underwent a sham operation. After 10 days, rats were decapitated. Each bladder was excised and BSM strips placed in an organ bath where contractile and relaxant responses were studied.

Results

Contractile response of BSM to KCl decreased in the AH group. Increased response to muscarinic agonist carbachol was observed in the AH group. The relaxant response to adrenergic agonist isoprenaline was significantly decreased in the AH group, whereas non-receptor-dependent agonist papaverine was unchanged in 2 groups.

Conclusion

Bladder smooth muscle reactivity is affected by the formation of hydrocephalus essentially by both receptor-dependent and non-receptor-dependent mechanisms. This pathway may be a novel target for the pharmacologic treatment of bladder dysfunction secondary to hydrocephalus.     

Sodium channel-blocking agents are not of benefit to rats with kaolin-induced hydrocephalus

OBJECTIVE: Hydrocephalus causes damage to periventricular white matter at least in part through chronic ischemia. The sodium channel-blocking agents mexiletine and riluzole have been shown to be of some protective value in various models of neurological injury. We hypothesized that these agents would ameliorate the effects of experimental childhood-onset hydrocephalus. METHODS: Hydrocephalus was induced in 4-week-old rats by injection of kaolin into the cisterna magna. Tests of cognitive and motor function were performed on a weekly basis. In a blinded and randomized manner, mexiletine (0.7, 7, or 42 mg/kg/d) or riluzole (1.4 or 13.6 mg/kg/d) was administered by osmotic minipump for 2 weeks, beginning 2 weeks after induction of hydrocephalus. The brains were then subjected to histopathological and biochemical analyses. RESULTS: Compared with untreated hydrocephalic rats, neither mexiletine nor riluzole was associated with a protective effect on behavioral, structural, or biochemical abnormalities. CONCLUSION: Protection of hydrocephalic brains through pharmacological sodium channel blockade is probably an approach not worth pursuing.     

Renal and biliary abnormalities in a new murine model of autosomal recessive polycystic kidney disease

Current models of autosomal recessive polycystic kidney disease (ARPKD) fail to demonstrate biliary abnormalities in association with renal cysts. We therefore studied a new murine model of ARPKD in which dual renal tubular and biliary epithelial abnormalities are present. Affected homozygous animals typically die 1 month postnatally in renal failure with progressively enlarged kidneys. Renal cysts shift in site from inner cortical proximal tubules at birth to collecting tubules 20 days later, as determined by segment-specific lectin binding. Increased numbers of mitosis were demonstrated in proximal and collecting tubular cysts. In addition, epithelial hyperplasia was demonstrated morphometrically in the intra- and extrahepatic biliary tract of affected animals. The number of intrahepatic biliary epithelial cells was increased by 50% on postnatal day 5 and by 100% on postnatal day 25 (P<0.01). Despite an increased frequency of chaotic portal areas in mice with renal cysts, no intrahepatic cysts or shape abnormalities of the biliary lumen were detected using biliary casts and morphometry. Additionally there was nonobstructive hyperplastic dilatation of the extrahepatic biliary tract which was linked in all animals to the presence of renal cysts. The hyperplastic abnormalities in both renal and biliary epithelium make this new mouse strain a good model for the study of the dual organ cellular pathophysiology of ARPKD.     

Angiotensin type 2 receptor is important in the normal development of the ureter

 In humans, the actions of angiotensin II are transduced through the AT1 and AT2 receptors which have recently been implicated in renal organogenesis. Polymorphisms in the human angiotensin II receptor genes have been linked to cardiovascular and nephrological disorders. In this study we evaluated 35 patients with either primary obstructive megaureter or posterior urethral valves. Each was genotyped for the A1166 AT1 polymorphism and the recently described A-1332G AT2 transition. The incidence of these genetic variants was also evaluated in normal controls without any ultrasonographic urological abnormalities. Similar to our previous findings in congenital urological abnormalities, the AT1 receptor genotype distribution did not differ between patients with either primary obstructive megaureter or posterior urethral valves versus controls. In contrast, compared with normal controls, there was a dramatic increase in the occurrence of the AT2 A-1332G transition in patients with primary obstructive megaureter (75.0% vs. 41.9% in controls, P<0.025). In patients with posterior urethral valves, there was no difference in the occurrence of the transition versus controls (36.9%, P=NS). Thus, there is no correlation between the AT1 receptor gene polymorphism and urological abnormalities. However there is an increased incidence in the AT2 genetic variant in patients with primary obstructive megaureter. Received: 2 March 1998 / Received: 1 July 1998 / Accepted: 6 July 1998     

Influence of the rate of ventricular enlargement on the white matter water content in progressive feline hydrocephalus

The effectiveness of transependymal absorption of cerebrospinal fluid in hydrocephalus was studied by correlating the measured water content of feline hydrocephalic white matter with the rate of enlargement of the ventricles. Two groups of cats were subjected to opening of either the calvaria or the calvaria and dura before the intracisternal injection of kaolin to obtain two profiles of ventricular enlargement. The water content 1, 2, and 3 mm from the lateral ventricles was measured in each group using the dry/wet weight and microgravimetric techniques after sacrificing the animals in each group at 2, 3, or 6 weeks after inducing hydrocephalus. In the animals with both calvarial and dural opening, the ventricles enlarged rapidly in the first 2 to 3 weeks and then continued to increase but at a slower rate. Concomitant with this early increase of ventricular size was a progressive increase in white matter water content both adjacent to and remote from the ventricles, which continued through 6 weeks. When only the calvaria was opened, ventricular size increased gradually, but continued to increase at a constant rate throughout the 6 weeks. Water content adjacent to the ventricle did not increase until the 3rd week, with little spread to adjacent areas by the 6th week. The central canals of the spinal cord were enlarged in both groups at all sampling levels. Neither increased periventricular water nor dilatation of the central canal was associated with stabilization of ventricular size in these studies. The authors conclude that these pathways are not sufficient to arrest the hydrocephalic process in these models.     

An updated model of hydrocephalus in sheep to evaluate the performance of a device for ambulatory wireless monitoring of cerebral pressure through shunts

BackgroundCerebrospinal fluid (CSF) diversion by shunts is the most common surgical treatment for hydrocephalus. Though effective, shunts are associated with risk of dysfunction leading to multiple surgical revisions, affecting patient quality-of-life and incurring high healthcare costs. There is a need for ambulatory monitoring systems for life-long assessment of shunt status. The present study aimed to develop a preclinical model assessing the feasibility of our wireless device for continuous monitoring of cerebral pressure in shunts.MethodsWe first adapted a previous hydrocephalus model in sheep, which used an intracisternal kaolin injection. Seven animals were used to establish the model, and 1 sheep with naturally dilated ventricles was used as control. Hydrocephalus was confirmed by clinical examination and brain imaging before inserting the ventriculoperitoneal shunts and the monitoring device allowing continuous measurement of the pressure through the shunt for a few days in 3 sheep. An external ventricular drain was used as gold standard.ResultsOur results showed that a reduction in kaolin dose associated to postoperative management was crucial to reduce morbidity and mortality rates in the model. Ventriculomegaly was confirmed by imaging 4 days after injection of 75 mg kaolin into the cisterna magna. For the implanted sheep, recordings revealed high sensitivity of our sensor in detecting fluctuations in cerebral pressure compared to conventional measurements.ConclusionsThis proof-of-concept study highlights the potential of this preclinical model for testing new shunt devices.     

Protective effect of nimodipine on behavior and white matter of rats with hydrocephalus

OBJECT: Hydrocephalus, a pathological dilation of the ventricles of the brain, causes damage to periventricular white matter, at least in part, through chronic ischemia. The authors tested the hypothesis that treatment with nimodipine, an L-type calcium channel-blocking agent with demonstrated efficacy in a range of cerebral ischemic disorders, would ameliorate the adverse effects of experimental hydrocephalus. METHODS: Hydrocephalus was induced in 3-week-old rats by injection of kaolin into the cisterna magna. The rats were treated by continuous administration of nimodipine or control vehicle for 2 weeks, beginning 2 weeks after induction of hydrocephalus. During the treatment period, the animals underwent repeated tests of motor and cognitive behavior. At the end of the treatment period, the rat brains were analyzed by histopathological and biochemical means. Nimodipine treatment prevented the declines in motor and cognitive behavior that were observed in untreated control rats. During the treatment period, ventricular enlargement, determined by magnetic resonance imaging, was equal in the two groups, although the corpus callosum was thicker in the treated rats. Myelin content in white matter and synaptophysin content in gray matter, an indicator of synapses, did not differ. CONCLUSIONS: The protective effect of nimodipine is most likely based on improved blood flow, although prevention of calcium influx-mediated proteolytic processes in axons cannot be excluded. Adjunctive pharmacological therapy may be beneficial to patients with hydrocephalus.     

A comparative study of alkaline phosphatase in calcifying cartilage,odontoblasts and the enamel organ

The enzyme alkaline phosphatase (AP) (EC 3.1.3.1) in three different calcification areas was studied by means of a spectrophotometric micro method using p-nitrophenylphosphate as a substrate. Rat maxillary incisor odontoblasts and enamel organ from the zones of matrix formation and maturation and tissue from rabbit metatarsal cartilage were allowed to react with the substrate in glycine-NaOH buffer at room temperature. The reaction was found to be linear for a minimum of 20 min. The pH optima for AP from these tissues were in the pH range of 10.0–10.3. In order to compare AP from the four calcification areas different parameters were studied. Heating at 56°C or 60°C for varying times revealed that the enzymes were almost completely inactivated after 10 min. Mg²⁺ ions activated the enzymes by about 25% at concentrations of 2.5 mM (enamel organ 1.25 mM); while only higher concentrations of Mg²⁺ had an inactivating effect, Ca²⁺ and PO ₄ ^3– ions were inactivating at varying concentrations. F^– ions show no effect on AP activity at concentrations below 250 mM (enamel organ 125 mM) but caused inactivation of the enzymes at about 50% at 1 M. EDTA was found to be a very effective AP inactivator at concentrations above 0.06 mM, whereas urea did not noticeably affect the enzyme reactions at concentrations below 1 M. At higher concentrations, inactivation was observed. In order to determine AP localization in the epiphyseal plate successive 40-m-thick, freeze-sectioned slices were analyzed. The activity was highest nearest the zone of cartilage calcification and decreased towards the reserve cell zone.It was concluded that the same AP isoenzyme is present in these quite different calcification loci.     

Correction of congenital hydrocephalus in utero II: Efficacy of in utero shunting

To study the effect of in utero ventricular decompression of hydrocephalus on brain development and prognosis, and to evaluate the function and possible complications of different shunt designs, we created fetal hydrocephalus in 28 fetal lambs and 17 fetal monkeys by injecting kaolin into the cisterna magna during the third trimester. One fetal lamb had indwelling intracranial subdural and amniotic cavity pressure catheters placed to study serial changes in the relationship of intracranial pressure (ICP) and amniotic fluid pressure (AFP) from the time of injection until term. Twenty hydrocephalic fetal lambs underwent ventricular decompression--ventriculoamniotic (V-A), N = 10; ventriculo-right atrial (V-RA), N = 9; and ventriculo-pleural (V-PL), N = 1--21 to 25 days after the kaolin was injected; seven hydrocephalic fetuses were left unshunted as controls (CON). Eight fetal monkeys underwent V-A decompression 14 to 21 days after kaolin injection; nine were left unshunted as controls. All animals were delivered by cesarean section near term, assessed for viability and their brains examined grossly and microscopically. After kaolin injection in the fetal lamb, ICP (r = 0.94) and ICP minus AFP (r = 0.93) rose in a linear fashion, while AFP showed no trend (r = 0.22). All unshunted newborn lambs and monkeys had split sutures, dilated ventricles, and thinned cortical mantle. Most shunted lambs showed anatomic improvement with decreased head circumference, overriding sutures, normal-sized ventricles, and improved survival. However, histopathology revealed marked white matter destruction. In contrast, most shunted monkeys showed little anatomic improvement. Both shunted and unshunted monkey brains showed a severe inflammatory ventriculitis. In both lambs and monkeys, shunting was associated with a variety of complications including subdural hematoma, subdural hygroma, shunt infection, shunt occlusion, and improper shunt tip placement. In this experimental model, in utero decompression of obstructive hydrocephalus improves overall survival, improves gross ventriculomegaly, does not improve histopathologic brain damage, and is associated with significant complications. The choice of the optimal shunt design and the effect on postnatal neurologic function requires further study. This work emphasizes the need for continuing research in an animal model prior to human application.     

Experimental hydrocephalus and hydrosyringomyelia in the cat

Fourty-six cats were made hydrocephalic and hydromyelic by means of an intracisternal kaolin injection. In 17 other cats hydrocephalus and syringohydromyelia were achieved by operative occlusion of the foramina Luschkae of the fourth ventricle. In both the kaolin treated animals and the animals whose outlets of the fourth ventricles were operatively obstructed a progressive dilatation of the ventricles and central canal occurred, which could be demonstrated and followed in 30 animals by ventriculography, myelography and/or contrast filling of the hydromyelic central canal. Coinciding with the dilatation of the central canal the clinical picture of a raised intracranial pressure due to obstructive hydrocephalus improved. The presented results suggest that the dilated central canal acts as a kind of natural by-pass between the ventricles and the spinal subarachnoid space. In order to determine the role of spinal kaolin arachnoiditis on spinal cyst formation and central canal dilatation in 13 animals, kaolin was locally applied in the lower thoracic region. The local spinal kaolin arachnoiditis had no influence on central canal dilatation or cyst formation.     

Experimental fetal hydrocephalus. Ventriculo-amniotic shunt

When the original idea was conceived 8 years ago to develop a surgical technique for the treatment of fetal hydrocephalus, the pathway towards prenatal surgery for this affection was totally unexplored. The operation appeared to be feasible because of the possibility of a ventriculo-amniotic shunt. The most important steps in our experimental studies in the ewe were creation of a fetal hydrocephalus by injection of a suspension of kaolin powder into cisterna magna; the treatment of the hydrocephalus by a mini-ventriculo-amniotic shunt, by cutting the cardiac end of a low pressure Pudenz pediatric catheter. Lambs were delivered by Cesarean two weeks before end of gestation. Coronal sections of brains of control and treated lambs showed reduction in hydrocephalus in the latter. These findings were the basis for the application of the method to treatment of human fetal hydrocephalus.     

Influence of the rate of ventricular enlargement on the ultrastructural morphology of the white matter in experimental hydrocephalus

The influence of the rate of ventricular enlargement on the morphology of hydrocephalic white matter was studied and correlated with previous studies of water content. Different rates of ventricular enlargement were obtained in two groups of cats by opening either the calvaria or the calvaria and the dura mater before injecting kaolin into the cisterna magna. Animals from each group underwent in vivo fixation of brain 2, 3, and 6 weeks after hydrocephalus was induced. Specimens of white matter were taken 1, 2, and 3 mm lateral to the ependymal surface of the lateral ventricles, imbedded, and examined using transmission electron microscopy. The ultrastructural changes associated with ventricular enlargement varied with the model used and the duration of hydrocephalus. Marked expansion of the extracellular space extending 2 mm lateral from the ependyma was found in the craniectomy-durectomy preparations examined 2 to 3 weeks after kaolin injection. Time-matched craniectomy preparations had less enlargement of the extracellular space that was confined to the white matter immediately adjacent to the ventricle. Marked glial reaction was observed in these areas in the early craniectomy preparations. When studied 6 weeks after hydrocephalus induction, both models had less expansion of the extracellular spaces compared to early observations. Glial reaction was found in both models, but was greater in the craniectomy model. The correlation of these morphological findings with the rate of ventricular enlargement and earlier studies of water content are discussed.