Intracisternal Injection Of Kaolin Research Articles

Vanadium administration ameliorates cortical structural and functional changes in juvenile hydrocephalic mice.

Vanadium is a prevalent neurotoxic transition metal with therapeutic potentials in some neurological conditions. Hydrocephalus poses a major clinical burden in neurological practice in Africa. Its primary treatment (shunting) has complications, including infection and blockage; alternative drug-based therapies are therefore necessary. This study investigates the function and cytoarchitecture of motor and cerebellar cortices in juvenile hydrocephalic mice following treatment with varying doses of vanadium. Fifty juvenile mice were allocated into five groups (n=10 each): controls, hydrocephalus-only, low- (0.15mg/kg), moderate- (0.3mg/kg), and high- (3.0mg/kg) dose vanadium groups. Hydrocephalus was induced by the intracisternal injection of kaolin and sodium metavanadate administered by intraperitoneal injection 72hourly for 28 days. Neurobehavioral tests: open field, hanging wire, and pole tests, were carried out to assess locomotion, muscular strength, and motor coordination, respectively. The cerebral motor and the cerebellar cortices were processed for cresyl violet staining and immunohistochemistry for neurons (NeuN) and astrocytes (glial fibrillary acidic protein). Hydrocephalic mice exhibited body weight loss and behavioral deficits. Horizontal and vertical movements and latency to fall from hanging wire were significantly reduced, while latency to turn and descend the pole were prolonged in hydrocephalic mice, suggesting impaired motor ability; this was improved in vanadium-treated mice. Increased neuronal count, pyknotic cells, neurodegeneration and reactive astrogliosis were observed in the hydrocephalic mice. These were mostly mitigated in the vanadium-treated mice, except in the high-dose group where astrogliosis persisted. These results demonstrate a neuroprotective potential of vanadium administration in hydrocephalus. The molecular basis of these effects needs further exploration.

Celecoxib attenuates neuroinflammation, reactive astrogliosis and promotes neuroprotection in young rats with experimental hydrocephalus

Hydrocephalus is a neurological condition with altered cerebrospinal fluid flow (CSF). The treatment is surgical and the most commonly used procedure is ventricle-peritoneal shunt. However, not all patients can undergo immediate surgery or achieve complete lesion reversal. Neuroprotective measures are valuable in such cases. It was evaluated whether the use of celecoxib, a selective inhibitor of COX-2, associated or not with ventricular-subcutaneous derivation, could offer benefits to the brain structures affected by experimental hydrocephalus. Seven-day-old male Wistar Hannover rats induced by intracisternal injection of kaolin 15% were used, divided into five groups with ten animals each: intact control (C), untreated hydrocephalus (H), hydrocephalus treated with celecoxib 20 mg/kg intraperitoneal (HTC), hydrocephalus treated with shunt (HTS) and hydrocephalus treated with shunt and celecoxib 20 mg/kg intraperitoneal (HTCS). Celecoxib was administered for 21 consecutive days, starting the day after hydrocephalus induction and continuing until the end of the experimental period. The surgery was performed seven days after inducing hydrocephalus. Multiple assessment methods were used, such as behavioral tests (water maze and open field), histological analysis (hematoxylin and eosin), immunohistochemistry (caspase-3, COX-2, and GFAP), and ELISA analysis of GFAP. The results of the behavioral and memory tests indicated that celecoxib improves the neurobehavioral response. The improvement can be attributed to the reduced neuroinflammation (p < 0.05), and astrogliosis (p < 0.05) in different brain regions. In conclusion, the results suggest that celecoxib holds great potential as an adjuvant neuroprotective drug for the treatment of experimental hydrocephalus.

Memantine associated with ventricular-subcutaneous shunt promotes behavioral improvement, reduces reactive astrogliosis and cell death in juvenile hydrocephalic rats

Hydrocephalus is defined as the accumulation of cerebrospinal fluid in the brain ventricles. The usual treatment of hydrocephalus is surgical (shunt), but not all patients can undergo treatment immediately after diagnosis. Thus, neuroprotective measures were tested to minimize the tissue damage involved. Memantine is a non-competitive antagonist of the N-methyl-D-aspartate (NMDA) receptor, which has shown a neuroprotective action in neurodegenerative diseases. This study aimed to evaluate the neuroprotective response of memantine in animals treated with or without a ventricular-subcutaneous shunt. Seven-day-old male Wistar rats induced by intracisternal injection of kaolin were used, divided into five groups: intact control (n = 10), hydrocephalic (n = 10), hydrocephalic treated with memantine (20 mg/kg/day) (n = 10), hydrocephalic treated with shunt (n = 10), hydrocephalic treated with shunt and memantine (20 mg/kg/day) (n = 10). Memantine administration was started on the day after hydrocephalus induction and continued until the last day of the experimental period, totaling 21 consecutive days of drug application. The CSF shunt surgery was performed seven days after hydrocephalus induction. Behavioral tests (open field, and modified Morris water maze), histological, and immunohistochemical evaluations were performed. Treatment with memantine resulted in significant improvement (p < 0.05) in sensorimotor development, preservation of spatial memory, reduction of astrocytic reaction in the corpus callosum, cortex, and germinal matrix. When associated with the shunt, it has also been shown to reduce the cell death cascade. It is concluded that memantine is a promising adjuvant drug with beneficial potential for the treatment of lesions secondary to hydrocephalus.

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 75mg 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.

Neurobehavioural changes and morphological study of cerebellar purkinje cells in kaolin induced hydrocephalus.

Cerebellar abnormalities are commonly associated with hydrocephalus. However, the effect of hydrocephalus on the otherwise normal cerebellum has been largely neglected. This study assesses the morphological changes in the Purkinje cells in relation to cerebellar dysfunction observed in juvenile hydrocephalic rats. Fifty-five three-week old albino Wistar rats were used, hydrocephalus was induced by intracisternal injection of kaolin (n = 35) and others served as controls (n = 20). Body weight measurements, hanging wire, negative geotaxis, and open field tests were carried out at the onset and then weekly for 4weeks, rats were killed, and their cerebella processed for Hematoxylin and Eosin, Cresyl violet and Golgi staining. Qualitative and quantitative studies were carried out; quantitative data were analyzed using two-way ANOVA and independent T tests at p < 0.05. Hydrocephalic rats weighed less than controls (p = 0.0247) but their cerebellar weights were comparable. The hydrocephalic rats had a consistently shorter latency to fall in the hanging wire test (F(4,112) = 18.63; p < 0.0001), longer latency to turn in the negative geotaxis test (F(4,112) = 22.2; p < 0.0001), and decreased horizontal (F(4,112) = 4.172, p = 0.0035) and vertical movements (F(4,112) = 4.397; p = 0.0024) in the open field test than controls throughout the 4weeks post-induction. Cellular compression in the granular layer, swelling of Purkinje cells with vacuolations, reduced dendritic arborization and increased number of pyknotic Purkinje cells were observed in hydrocephalic rats. Hydrocephalus caused functional and morphological changes in the cerebellar cortex. Purkinje cell loss, a major pathological feature of hydrocephalus, may be responsible for some of the motor deficits observed in this condition.

Hydrocephalus-Induced Changes in the Endocrine Hypothalamus of the Hamster

Hydroceplanllus-induced changes in intracranial pressure (ICP), ventricular size, periventricular edema and erytlirocyte density(ED), median eminence thickness, and pituitary gland morphology were determined in adult female hamsters (Mesocricetus auratus). Hydrocephalus (HC) was induced by intracisternal injection of kaolin (0.03 ml, 50 mg/ml saline); controls did not receive kaolin. Animais were chronically cannulated and ICP measured periodically (Camino V 420). At selecied times control and treated animals were decapitated, brains removed with the pituitary gland attached and fixed by immersion in formalin. Coronal brain slices containing the paraventricular nuclei (PVN), supraoptic nuclei (SON), suprachiosmatic nuclei (SCN), subfornical organ (SFO) and median eminence (ME) were prepared using a rodent brain matrix slicer and ventricular arca was quantitated by morphometric analysis (Jandel Video Analysis System). Samples were collected from the cortex and periventricular white matter (containing the PVN, SON, and SCN) and the median eminence. The whole pituitary gland was also collected for determination of specific gravity by linear density column method. Erythrocyte Densiry was assessed by immersing hydrocephalic brain slices containing the select nuclei in Karnoviskys fixative on day 9 post HC induction, and in simerythrocytes stained for endogenous peroxidase by tretramethyl benzidine cylochemistry to facilitate visualization. Previous studies in our laboratory have establislied that HC can result in alterations in estrous cycle, water balance, food intake and growth. The result in part from decrease perfusion of the endocrine liypothalamus and pituitary gland, edema and pressure-induced changes in the median eminence structures.

Expression of Aquaporin 1 and 4 in the Choroid Plexus and Brain Parenchyma of Kaolin-Induced Hydrocephalic Rats.

ObjectiveAquaporin (AQP) is a recently discovered protein that regulates water homeostasis. The present study examines changes in AQP 1 and 4 in kaolin induced experimental hydrocephalic rats to elucidate the pathophysiology of water homeostasis in the disease.MethodsHydrocephalus was induced by percutaneous intracisternal injection of kaolin. The brain parenchyma and choroid plexus were obtained at 3, 7, 14 and 30 days after injection. Protein expressions of AQP 1 and 4 were measured by western blot, immunohistochemistry (IHC) and immunofluorescence (IF) stains.ResultsIn the choroid plexus of the kaolin-induced hydrocephalus group, AQP 1 expression identified by western blot exhibited sharp decrease in the early stage (55% by the 3rd day and 22% by the 7th day), but indicated a 2.2-fold increase in the later stage (30th day) in comparison with control groups. In the parenchyma, a quantitative measurement of AQP 4 expression revealed variable results on the 3rd and 7th days, but indicated expression 2.1 times higher than the control in the later stage (30th day). In addition, the IHC and IF findings supported the patterns of expression of AQP 1 in the choroid plexus and AQP 4 in the parenchyma.ConclusionExpression of AQP 1 decreased sharply in the choroid plexus of acute hydrocephalus rats and increased at later stages. Expression of AQP 4 in the brain parenchyma was variable in the early stage in the hydrocephalus group, but was higher than in the control in the later stage. These findings suggest a compensating role of AQPs in water physiology in hydrocephalus.

Differential vulnerability of white matter structures to experimental infantile hydrocephalus detected by diffusion tensor imaging.

The differential vulnerability of white matter (WM) to acute and chronic infantile hydrocephalus and the related effects of early and late reservoir treatment are unknown, but diffusion tensor imaging (DTI) could provide this information. Thus, we characterized WM integrity using DTI in a clinically relevant model. Obstructive hydrocephalus was induced in 2-week-old felines by intracisternal kaolin injection. Ventricular reservoirs were placed 1 (early) or 2 (late) weeks post-kaolin and tapped frequently based solely on neurological deficit. Hydrocephalic and age-matched control animals were sacrificed 12 weeks postreservoir. WM integrity was evaluated in the optic system, corpus callosum, and internal capsule prereservoir and every 3 weeks using DTI. Analyses were grouped as acute (<6 weeks) or chronic (≥6 weeks). In the corpus callosum during acute stages, fractional anisotropy (FA) decreased significantly with early and late reservoir placement (p = 0.0008 and 0.0008, respectively), and diffusivity increased significantly in early (axial, radial, and mean diffusivity, p = 0.0026, 0.0012, and 0.0002, respectively) and late (radial and mean diffusivity, p = 0.01 and 0.0038, respectively) groups. Chronically, the corpus callosum was thinned and not detectable by DTI. FA was significantly lower in the optic chiasm and tracts (p = 0.0496 and 0.0052, respectively) with late but not early reservoir placement. In the internal capsule, FA in both reservoir groups increased significantly with age (p < 0.05) but diffusivity remained unchanged. All hydrocephalic animals treated with intermittent ventricular reservoir tapping demonstrated progressive ventriculomegaly. Both reservoir groups demonstrated WM integrity loss, with the CC the most vulnerable and the optic system the most resilient.

The relationship between ventricular dilatation, neuropathological and neurobehavioural changes in hydrocephalic rats

BackgroundThe motor and cognitive deficits observed in hydrocephalus are thought to be due to axonal damage within the periventricular white matter. This study was carried out to investigate the relationship between ventricular size, cellular changes in brain, and neurobehavioural deficits in rats with experimental hydrocephalus.MethodsHydrocephalus was induced in three-week old rats by intracisternal injection of kaolin. Behavioural and motor function were tested four weeks after hydrocephalus induction and correlated to ventricular enlargement which was classified into mild, moderate or severe. Gross brain morphology, routine histology and immunohistochemistry for oligodendrocytes (CNPase), microglia (Iba-1) and astrocytes (GFAP) were performed to assess the cellular changes.ResultsDecreases in open field activity and forelimb grip strength in hydrocephalus correlated with the degree of ventriculomegaly. Learning in Morris water maze was significantly impaired in hydrocephalic rats. Gradual stretching of the ependymal layer, thinning of the corpus callosum, extracellular oedema and reduced cortical thickness were observed as the degree of ventriculomegaly increased. A gradual loss of oligodendrocytes in the corpus callosum and cerebral cortex was most marked in the severely-hydrocephalic brains, whereas the widespread astrogliosis especially in the subependymal layer was most marked in the brains with mild hydrocephalus. Retraction of microglial processes and increase in Iba-1 immunoreactivity in the white matter was associated ventriculomegaly.ConclusionsIn hydrocephalic rats, oligodendrocyte loss, microglia activation, astrogliosis in cortical areas and thinning of the corpus callosum were associated with ventriculomegaly. The degree of ventriculomegaly correlated with motor and cognitive deficits.

Neuroendoscopic surgery in empty ventricular system under continuous gas infusion experimental study of pressure changes and complications

The most important limitations to endoscopic procedures in the ventricular system of the brain are due to the constraint of working inside a fluid. The evacuation of cerebrospinal fluid (CSF) from the ventricles is performed often in microsurgical interventions using a surgical microscope. This study aimed at studying the evacuation of CSF during neuroendoscopic surgery in animals while infusing gas to avoid ventricular collapse. Hydrocephalus was provoked in five adult New Zealand rabbits by intracisternal injection of kaolin. Endoscopic intervention was performed later; fluid was given as a continuous infusion at constant speed into the CSF for 3min. In the next stage, CSF was evacuated from the ventricles, which were infused with gas at a stable rate for the same amount of time. The intracranial pressure (ICP) of the rabbits was recorded during both operations. The animals were sacrificed and the brain subjected to pathology examination at the end of the experiment. Mean ICP value in the rabbit ventricle was 19.1 while working in CSF and 17.6 when working in air. The difference by a paired test was statistically significant for each individual rabbit except one. The ICP measurement, however, was never lower than the ambient pressure, even while working in continuous gas infusion. No epidural or subdural hematomas were found at autopsy. Endoscopic surgery is feasible in a ventricular system that has been insufflated with gas after CSF has been evacuated. During the experiment, however, steadily diminishing ICP values were measured. As a result, new devices, such as small-flow insufflators able to perform sensitive pressure adjustments are needed.

Hydrocephalus induces dynamic spatiotemporal regulation of aquaporin-4 expression in the rat brain.

BackgroundThe water channel protein aquaporin-4 (AQP4) is reported to be of possible major importance for accessory cerebrospinal fluid (CSF) circulation pathways. We hypothesized that changes in AQP4 expression in specific brain regions correspond to the severity and duration of hydrocephalus.MethodsHydrocephalus was induced in adult rats (~8 weeks) by intracisternal kaolin injection and evaluated after two days, one week and two weeks. Using magnetic resonance imaging (MRI) we quantified lateral ventricular volume, water diffusion and blood-brain barrier properties in hydrocephalic and control animals. The brains were analysed for AQP4 density by western blotting and localisation by immunohistochemistry. Double fluorescence labelling was used to study cell specific origin of AQP4.ResultsLateral ventricular volume was significantly increased over control at all time points after induction and the periventricular apparent diffusion coefficient (ADC) value significantly increased after one and two weeks of hydrocephalus. Relative AQP4 density was significantly decreased in both cortex and periventricular region after two days and normalized after one week. After two weeks, periventricular AQP4 expression was significantly increased. Relative periventricular AQP4 density was significantly correlated to lateral ventricular volume. AQP4 immunohistochemical analysis demonstrated the morphological expression pattern of AQP4 in hydrocephalus in astrocytes and ventricular ependyma. AQP4 co-localized with astrocytic glial fibrillary acidic protein (GFAP) in glia limitans. In vascular structures, AQP4 co-localized to astroglia but not to microglia or endothelial cells.ConclusionsAQP4 levels are significantly altered in a time and region dependent manner in kaolin-induced hydrocephalus. The presented data suggest that AQP4 could play an important neurodefensive role, and may be a promising future pharmaceutical target in hydrocephalus and CSF disorders.

Reactive astrocytosis, microgliosis and inflammation in rats with neonatal hydrocephalus

The deleterious effects of hydrocephalus, a disorder that primarily affects children, include reactive astrocytosis, microgliosis and inflammatory responses; however, the roles that these mechanisms play in the pathophysiology of hydrocephalus are still not clear in terms of cytopathology and gene expression. Therefore we have examined neuroinflammation at both the cellular and the molecular levels in an experimental model of neonatal obstructive hydrocephalus. On post-natal day 1, rats received an intracisternal injection of kaolin to induce hydrocephalus; control animals received saline injections. Prior to sacrifice on post-natal day 22, animals underwent magnetic resonance imaging to quantify ventricular enlargement, and the parietal cortex was harvested for analysis. Immunohistochemistry and light microscopy were performed on 5 hydrocephalic and 5 control animals; another set of 5 hydrocephalic and 5 control animals underwent molecular testing with Western blots and a gene microarray. Scoring of immunoreactivity on a 4-point ranking scale for GFAP and Iba-1 demonstrated an increase in reactive astrocytes and reactive microglia respectively in the hydrocephalic animals compared to controls (2.90 ± 0.11 vs. 0.28 ± 0.26; 2.91 ± 0.11 vs. 0.58 ± 0.23, respectively). Western blots confirmed these results. Microarray analysis identified significant (1.5-fold) changes in 1729 of 33,951 genes, including 26 genes out of 185 genes (26/185) in the cytokine–cytokine receptor interaction pathway, antigen processing and presentation pathways (15/66), and the apoptosis pathway (10/69). Collectively, these results demonstrate alterations in normal physiology and an up-regulation of the inflammatory response. These findings lead to a better understanding of neonatal hydrocephalus and begin to form a baseline for future treatments that may reverse these effects.

Brain damage in experimental neonatal hydrocephalus: correlations between diffusion tensor imaging and cytopathology

Materials and methods Obstructive hydrocephalus was induced by intracisternal injection of kaolin on postnatal day 1 (P1); age-matched control animals were either intact or received intracisternal injections of saline. Six animals (3 hydrocephalics and 3 intact controls) were imaged in vivo at 8-9 days of age (P8-9) and then sacrificed by cardiac perfusion of paraformaldehyde. Four animals (2 hydrocephalics and 2 saline controls) were sacrificed at postnatal day 21 (P21) and paraformaldehyde-fixed brains were imaged ex vivo with a Bruker 7 T MRI scanner. DTI was acquired in 6 directions to obtain measurements of the directionality of water diffusion through tissue (Fractional Anisotropy, FA; 0 = isotropic where water can move freely in any direction; 1 = anisotropic where water can move in only one direction) and the magnitude of diffusivity of water in tissue (Mean Diffusivity, MD). Values were computed bilaterally in the genu of the corpus callosum (gCC), external capsule (EC), internal capsule (IC), and cortical gray matter (Ctx). Results At P8-9 ventriculomegaly was severe and by P21 had progressed to where the periventricular white matter and internal capsule were so thin that DTI could only be reliably performed ex vivo. At both times FA values were significantly reduced in the gCC (p < 0.001) but not the EC, IC or Ctx. There was a trend toward higher FA values at P21 than at P8/9 for both hydrocephalic rats and normal controls. In contrast, MD values increased only in the EC. Conspicuous gliosis was prevalent in all structures examined but differed depending on cell type. Younger animals showed a more robust reaction of microglial cells compared to 21-day old hydrocephalics. Astrocytes exhibited the opposite pattern with a more robust reaction in the older animals.

Proliferating cell populations in experimentally-induced hydrocephalus in developing rats

To examine the fate of proliferating brain cells in hydrocephalus (Hydro), experimental Hydro was induced in neonatal rats by intracisternal injection of kaolin and, 3 weeks later, the rats were injected with bromodeoxyuridine (BrdU). The BrdU (+) cells were immunohistochemically analyzed by using antibodies against neural (nestin), neuronal (NeuN) and glial (GFAP and MBP) markers in the posterior cerebrum. The percentage of nestin expression for the BrdU (+) cells was 8% in control and increased from 17% in the Hydro to 33% in the Hydro at an earlier stage after the shunt procedure, but was restored to 6% in the Hydro at a later stage after the shunt procedure. The percentages of GFAP expression showed a similar tendency to those of nestin expression. The BrdU (+) cells did not express either NeuN or MBP throughout the experiments.

Study of corpus callosum in experimental hydrocephalic wistar rats

PURPOSE: Hydrocephalus causes countless cerebral damages, especially on the structures around the ventricles. Hydrocephalic children present deficiencies in the nonverbal skills more than in the verbal skills, and not always revertible with an early treatment. As the corpus callosum has an important role in the nonverbal acquisition it is possible that the injuries in this structure are responsible for the cognitive dysfunctions of these children. This present study tries to establish the alterations caused by hydrocephalus on the corpus callosum of developing Wistar rats, induced by intracisternal injection of kaolin. METHODS : Seven, fourteen and twenty one days after the injection, the animals were killed, and the corpus callosum was dissected and prepared for the study of the axonal fibers. RESULTS AND CONCLUSION: The seven-day old rats in hydrocephalus development presented a delay in myelination in relation to the control rats. With the fourteen-day old rats in hydrocephalus development the corpus callosum showed a recovery of myelin, but with the twenty one-day old rats in hydrocephalus development the axonal fibers were damaged and reduced in number.

Pathology of the hippocampus in experimental feline infantile hydrocephalus

Hydrocephalus is responsible for many pediatric neurological deficits presumed to be caused by neocortical pathophysiology. Relatively little is known about the role of non-neocortical CNS structures in this condition. In the present work experimental infantile hydrocephalus produced by intracisternal kaolin injection was studied in a neonate kitten model. The hippocampal formation was processed for electron microscopy, and the neuropil of the CA3 region was examined in untreated, severely hydrocephalic and age-matched normal animals. Both macroscopically and microscopically the thickness of the hippocampus was not decreased. Hippocampal pyramidal neurons were found in varying stages of cytoplasmic densification, and dendritic and axonal processes exhibited hydropic cellular deterioration. The number of synaptic contacts was decreased. However, there was no indication of edematous extracellular space and the ependymal covering of the hippocampus was intact. The macroscopic structural integrity of the hippocampus, as well as the dendritic, axonal and synaptic alterations, suggest that the dark pyramidal neurons are the result of deafferentation, which may have profound effects on learning and memory. [Neurol Res 2000; 22 :29-36]

Angiotensin II receptor content within the circumventricular organs increases after experimental hydrocephalus in rats.

Hydrocephalus is known to cause various endocrinological abnormalities. These abnormalities are either though a direct effect on anterior hypothalamus or pituitary gland. However almost nothing is known about the effects of hydrocephalus on the intrinsic angiotensin system of the brain. The aim of this study is to investigate the effect of hydrocephalus on neurotransmitter-rich circumventricular organ systems. Such an effect was investigated by means of angiotensin receptor content in subfornical organ (SFO), organum vasculosum lamina terminalis (OVLT), area postrema (AP) and the median eminence (ME). Experimental hydrocephalus was created in rats by the intracisternal kaolin injection method as described by Shapiro et al. The receptor content was measured at 4-6 weeks by in-vitro autoradiography method as described by Israel et al. Angiotensin II receptor content in hydrocephalic animals was found to be statistically increased in SFO, OVLT and ME but not in AP when compared with the normal animals. Receptor content was found to have increased by 182.4% at SFO, 76.7% at ME, 7.7% at AP and 22.1% at OVLT after kaolin injection. These findings may indicate the possible role of CVO's on pathological conditions such as hydrocephalus.

Kaolin-induced hydrocephalus in the hamster: temporal sequence of changes in intracranial pressure, ventriculomegaly and whole-brain specific gravity.

The development of kaolin-induced hydrocephalus in adult hamsters was monitored by measuring changes in intracranial pressure (ICP), ventriculomegaly (VG) and whole-brain specific gravity (SG). Controls were intact or sham operated animals. Relative to controls, ICP of experimental animals increased at 24 h post intracisternal kaolin injection (by approximately 7-fold), reached a maximum on day 6 (by approximately 12-fold) and remained markedly elevated through day 15 (by approximately 5-fold). Ventricles differed in time of onset of distension (third: day 1, lateral: day 2, fourth: day 4) and in time of maximum ventriculomegaly (fourth: day 6; third: day 7; and lateral: day 9). Ventricular distension resulted in alterations in the ependyma; cilia were lost and apical cell surfaces were distorted. The ependyma was ruptured and the subjacent neuropil was exposed to the cerebrospinal fluid in some regions. Whole-brain SG remained constant in controls but declined in hydrocephalic hamsters after day 3 post-kaolin injection and reached its nadir on day 9 when whole-brain water content was 18% greater than in controls. Consistent with the fact that causal relationships exist between increased ICP, ventricular distension and brain edema, the alterations in each parameter occurred sequentially rather than simultaneously, and the time-course of each manifestation of hydrocephalus differed. The data suggest that the pathophysiology of kaolin-induced hydrocephalus in the hamster is tri-phasic: an initial period of rapid change, a brief interval of maximum alteration, and a subsequent period of compensation.

Experimental syringomyelia: Late ultrastructural changes of spinal cord tissue and magnetic resonance imaging evaluation

In human hydrosyringomyelia and in the late stage of experimental syringomyelia, the spinal cord tissue adjacent to the syrinx is exposed to a similar pathophysiologic condition. We investigated the ultrastructural changes in the late stages of kaolin-induced syringomyelia, and in addition, we presented magnetic resonance imaging (MRI) findings of the cervicomedullary junction and syrinx, and the nature of edema in the spinal cord of this experimental model. Syringomyelia was induced in rabbits by intracisternal injection of kaolin. MRI was performed at 6 weeks, and 6 and 12 months following injection, and the animals were killed by transcardial perfusion of formaldehyde solution and examined by transmission electron microscopy. Evans blue was injected intravenously in six rabbits, 6 weeks and 12 months following kaolin injection and was examined by confocal laser scanning microscopy. MRI showed that the syrinx communicated with the fourth ventricle in most animals. Demyelination of varying degrees and slight edematous change were seen in the perisyrinx white matter. No extravasation of Evans blue was seen by confocal microscopy. Abundant astrocytic proliferation with a large number of glial filaments was seen at the margin of the syrinx and between the axons in the perisyringeal region. The perivascular space enlargement occurred in both the gray and white matter. The endothelial junctions appeared intact. Regenerating axons and remyelination by oligodendrocytes were seen occasionally. The MRI confirmed the communication between the fourth ventricle and the syrinx. The ultrastructural changes were almost identical to those of the early stage syrinx, but the astrocytic proliferation was more severe, and the edema was less in the late stage. The perisyrinx edema appeared to be of the interstitial type, as in hydrocephalus. Axonal degeneration and demyelination continued with abortive attempt at regeneration and remyelination in the less edematous late stage, which might be the cellular basis for the persistence or worsening of clinical symptoms and signs in the chronic stage of syringomyelia even after surgical treatment.

Improvement of cortical morphology in infantile hydrocephalic animals after ventriculoperitoneal shunt placement.

As a sequel to our previous descriptions of the pathological changes induced by hydrocephalus in the infantile cerebral cortex, the study presented here has evaluated the effects of surgical decompression on cortical cytology and cytoarchitecture. Hydrocephalus was induced in 14 kittens by the intracisternal injection of kaolin at 4 to 11 days of age. Nine of these hydrocephalic animals received low-pressure ventriculoperitoneal shunts at 9 to 15 days after kaolin injection; these animals were monitored preoperatively and postoperatively by ultrasound and were killed at various postshunt intervals up to 30 days. Five normal or saline-injected animals served as age-matched controls. At the time of shunt placement, the ventricular index confirmed that all recipient animals had attained moderate or severe degrees of ventriculomegaly. Within 3 days after shunt placement, the size of the lateral ventricles had decreased to control levels and was accompanied by rapid and dramatic improvements in behavior and skull ossification. When the animals were killed, gross inspection revealed that about half of the animals exhibited mild to moderate ventriculomegaly, with cortical mantles 50 to 80% their normal thickness. Tissue from frontal (primary motor), parietal (association), and occipital (primary visual) cortical areas was processed for light microscopic analysis. Pyknotic or dark shrunken neurons, which are found typically in hydrocephalic brains, were observed only occasionally in the cortex of shunted animals. Gliosis and mild edema were prevalent, however, in the periventricular white matter. The laminae of the cerebral cortex could be identified in all shunted animals. In those animals with mild residual ventriculomegaly, the entire cortical mantle was somewhat compressed, as evidenced by an increased packing density of neurons. Furthermore, the somata of some neurons were disoriented. Overall, these results indicate that most of the morphological characteristics of the cerebral cortex are preserved after surgical decompression and suggest that ventriculoperitoneal shunts may prevent neuronal damage and/or promote neuronal repair.