Experimental Obstructive Hydrocephalus Research Articles

Behavioral and Biochemical Features of the Course and Surgical Treatment of Experimental Obstructive Hydrocephalus in Young Rats

Introduction: Hydrocephalus is a multifactorial disease, affecting the dynamics of cerebrospinal fluid (CSF) and leading to severe neurological impairment in children; in spite of the recent advances in hydrocephalus research, it has many physiopathological aspects that still remain poorly understood, especially after treatment. Objectives: To analyze the clinical, radiological, histopathological, and biochemical aspects of kaolin-induced hydrocephalus in an experimental model, both in the acute phase and after shunt treatment, by means of behavioral tests, magnetic resonance imaging (MRI) scans, histopathological studies, and level of inflammatory interleukins in the CSF. Methods: Seven-day-old Wistar rats were used and subdivided into three subgroups: treated hydrocephalic (n = 24), untreated hydrocephalic (n = 17), and controls (n = 5). The hydrocephalic groups underwent cisternal injection of 15% kaolin for induction of hydrocephalus at 7 days of age. The treated group was submitted to a ventricular-subcutaneous shunt (VSCS) 1 week after induction. All animals were euthanized at 21 days of age. They underwent motor function and memory testing as well as brain MRI scans. Histopathological analysis for glial fibrillary acidic protein and Ki-67 was done, and CSF was collected for measurement of IL-1β, IL-6, and TNF-α. Results: The average time to reach the water maze platform was highest in the untreated hydrocephalic group. The magnetization transfer rates were 37.21 and 33.76 before and after shunting, respectively. The mean astrocyte counts were 2.45, 1.36, and 90.5 for shunted, untreated, and control animals, respectively. The mean CSF IL-1β concentrations were 62.3 and 249.6 pg/mL, the average IL-6 levels were 104.2 and 364.7 pg/mL, and the average TNF-α values were 4.9 and 170.5 pg/mL for the treated hydrocephalic group and the untreated group, respectively. Conclusions: Pups treated with a CSF shunt showed better performance on memory tests. VSCS did not revert demyelination caused by hydrocephalus. Likewise, reactive astrocytosis and cell proliferation over the germinal matrix were not reversed after shunting. Hydrocephalic animals had raised levels of inflammatory interleukins, which returned to normal after treatment.

Changes in Rat Brain Tissue Microstructure and Stiffness during the Development of Experimental Obstructive Hydrocephalus.

Understanding neural injury in hydrocephalus and how the brain changes during the course of the disease in-vivo remain unclear. This study describes brain deformation, microstructural and mechanical properties changes during obstructive hydrocephalus development in a rat model using multimodal magnetic resonance (MR) imaging. Hydrocephalus was induced in eight Sprague-Dawley rats (4 weeks old) by injecting a kaolin suspension into the cisterna magna. Six sham-injected rats were used as controls. MR imaging (9.4T, Bruker) was performed 1 day before, and at 3, 7 and 16 days post injection. T2-weighted MR images were collected to quantify brain deformation. MR elastography was used to measure brain stiffness, and diffusion tensor imaging (DTI) was conducted to observe brain tissue microstructure. Results showed that the enlargement of the ventricular system was associated with a decrease in the cortical gray matter thickness and caudate-putamen cross-sectional area (P < 0.001, for both), an alteration of the corpus callosum and periventricular white matter microstructure (CC+PVWM) and rearrangement of the cortical gray matter microstructure (P < 0.001, for both), while compression without gross microstructural alteration was evident in the caudate-putamen and ventral internal capsule (P < 0.001, for both). During hydrocephalus development, increased space between the white matter tracts was observed in the CC+PVWM (P < 0.001), while a decrease in space was observed for the ventral internal capsule (P < 0.001). For the cortical gray matter, an increase in extracellular tissue water was significantly associated with a decrease in tissue stiffness (P = 0.001). To conclude, this study characterizes the temporal changes in tissue microstructure, water content and stiffness in different brain regions and their association with ventricular enlargement. In summary, whilst diffusion changes were larger and statistically significant for majority of the brain regions studied, the changes in mechanical properties were modest. Moreover, the effect of ventricular enlargement is not limited to the CC+PVWM and ventral internal capsule, the extent of microstructural changes vary between brain regions, and there is regional and temporal variation in brain tissue stiffness during hydrocephalus development.

Deformation, microstructure and stiffness of the rat brain tissue during the development of experimental obstructive hydrocephalus

Understanding neural injury in hydrocephalus and how key physiological factors changes during the course of the disease in-vivo remain unclear. This study aims to describe brain deformation, microstructural and mechanical properties changes during obstructive hydrocephalus (HCP) development in a rat model using multimodal magnetic resonance (MR) imaging.

Sympathetic nervous control of cerebrospinal fluid production in experimental obstructive hydrocephalus

Hydrocephalus was induced in rabbits by cisternal injection of kaolin (0.5 ml of a 30 g 100 ml solution of hydrated aluminium silicate). The rate of bulk production of cerebrospinal fluid (CSF) was measured with a modified Pappenheimer [ 14C]inulin dilution technique in a ventriculoventricular perfusion system 3 days and 3 weeks after treatment. In the acute state of high-pressure hydrocephalus, CSF formation was reduced to almost one-half normal. Bilateral electrical stimulation of the cervical sympathetic nerves lowered the production rate by another 18%, with only an insignificant tendency to normalization after cessation of stimulation. In the chronic state of low-pressure hydrocephalus at 3 weeks after the kaolin injection, the rate of CSF formation was of the same magnitude as in animals studied after 3 days. However, sympathetic nerve stimulation now reduced the production rate by a further 39%, and prestimulation values were almost restored within 1 h after termination of stimulation. Thus, cranial sympathetic stimulation was very effective in reducing CSF formation in the chronic stage of low-pressure hydrocephalus. During acute high-pressure hydrocephalus, the sympathetic defence mechanisms were probably already recruited to such an extent that electrical activation of the sympathetic nerves was not able to further affect significantly the rate of CSF formation.

The rat in experimental obstructive hydrocephalus.

The effects of kaolin-induced hydrocephalus on CSF turnover was studied in rats by ventricular perfusion and the results compared to normals. The mean CSF formation rate measured in 20 normal rats was 2.83 microliter/min. Approximately three weeks after intracisternal kaolin, the mean CSF formation rate in 17 hydrocephalic rats was reduced by 40%. CSF absorption in hydrocephalic and normal rats varied linearly with perfusion pressures between -10 and 10 cm H2O. The response of CSF absorption rate to changes in intracranial pressure was decreased in hydrocephalic rats. Ventriculomegaly of hydrocephalic rats was associated with a dilated spinal cord central canal. This suggests that kaolin hydrocephalus alters CSF pathway in rats in a manner similar to that described previously in cats and dogs. Ventriculomegaly is limited by the supporting structures of the brain because the removal of the calvarium and dura after kaolin results in massive ventriculomegaly.

The pathology of experimental obstructive hydrocephalus. A scanning electron microscopic study.

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

Sympathetic Activity and Plateau Waves: Experiment in Cats

The nature of plateau waves is still unclear. In this experimental study, a possible relationship between the development of plateau waves and the activity of sympathetic vasomotor nerves was investigated using an experimental model of plateau waves produced in cats. Efferent discharge from the renal nerve activity (RNA) was recorded as an indicator for the sympathetic vasomotor tone. Intracranial pressure (ICP), systemic blood pressure (BP), endtidal CO2, cerebral blood flow (CBF), arterial blood gases, electroencephalograms (EEG) and somatosensory evoked potentials were monitored. Effects of hyperventilation and intravenous injection of mannitol on plateau waves were also studied. Experimental obstructive hydrocephalus was produced by injecting kaolin (250 mg of hydrated aluminum silicate) into the cisterna magna. Four weeks after the injection of kaolin, the central canal of the lumbar spinal cord was obliterated with a ligature placed around the dura mater. After the ligation of the spinal cord, ICP gradually increased, reaching a level of 30-100 mmHg during a period of 2-14 hours. Then, a plateau wave, a spontaneous abrupt rise in ICP up to the level of 70-160 mmHg with a duration of 4-33 minutes, was observed in all five animals. A decrease in RNA as well as in BP was observed corresponding to a rise in ICP at the initial phase of plateau waves. CBF, amplitude of EEG and somatosensory evoked potentials decreased at the peak of the plateau waves. There were no significant changes in endtidal CO2 and arterial pCO2. Plateau waves disappeared rapidly either by hyperventilation or mannitol administration. It was concluded that a temporary decrease in the sympathetic vasomotor tone in situations of increased intracranial pressure may initiate the development of plateau waves and metabolic factors secondary to brain ischemia may play a role in their perpetuation.

The pathology of experimental obstructive hydrocephalus. Electron microscopic observations.

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

Positive contrast ventriculography in cats with experimental obstructive hydrocephalus.

Cerebrospinal fluid pathways were studied in both normal and experimental obstructed hydrocephalic cats by positive contrast ventriculography. Either water soluble or insoluble contrast material was injected into the lateral cerebral ventricles, and radiographs were taken of the head and spinal cord. In the normal cat, the contrast material freely flowed throughout the spinal fluid spaces. The contrast material accumulated in the cisterna magna, and from there extended into the cranial and spinal subarachnoid spaces. In the kaolin-induced hydrocephalic cat, the outlets from the fourth ventricle were obstructed, and direct communication between the ventricular system and the subarachnoid spaces no longer existed. In these cats, the contrast material passed directly down the central canal of spinal cord and its movement was followed throughout the entire length of the canal. At the lower lumbar-sacral regions, the material perforated the cord and flowed into the subarachnoid space. At all levels, the central canal was enlarged and local dilatations were seen extending dorsally.

Continuous pressure monitoring in experimental obstructive hydrocephalus. II. The origin of undulating ventricular waves and periodic respirations.

Mayer waves and undulating ventricular waves were produced in hydrocephalic and nonhydrocephalic animals. Carotid sinus stimulation resulted in an increase in both wave forms, whereas carotid sinus denervation resulted in their diminution. The reflex pathway involved in the production of the waves constitutes a feedback mechanism between carotid sinus, the peripheral proprioceptor, and medullary vasomotor center. The ventricular fluid pressure wave forms are the intracranial manifestations of passively transmitted changes occurring in the systemic circulation secondary to dysfunction of the brain stem.

Continuous pressure monitoring in experimental obstructive hydrocephalus. I. The dynamics of acute ventricular obstruction.

Acute hydrocephalus was induced in five monkeys. Continuous recordings of Ventricular fluid pressure, respirations, and systemic arterial and venous pressures were performed for one hour before and 24 hours after ventricular obstruction. Ventricular fluid pressure was labile, increasing and decreasing over short time periods. During the increasing phase, two patterns of wave form emerged: waves associated with periodic respirations and monophasic waves with hyperpnea. The latter occurred at higher levels of pressure and represent more ominous development. Concomitant changes occurred in systemic arterial pressure. Undulations in systemic arterial pressure were associated with undulating ventricular waves, the same as Mayer waves. Ventricular waves closely resemble the one-per-minute and plateau waves recorded in humans. Caudal displacement of the brain stem (four monkeys) is believed to be the result of generalized hydrocephalus and increased intracranial pressure.

Alternate pathway for cerebrospinal fluid absorption in animals with experimental obstructive hydrocephalus

Transventricular absorption of cerebrospinal fluid (CSF) as an alternate pathway was examined in cats with experimental obstructive hydrocephalus. The isolated ventricular system was perfused under high (>13 cm H 2O) or low (≤0 cm H 2O) pressure with an artificial spinal fluid containing 131I-CSA (cat serum albumin). The uptake of radioactivity was measured in serial sections of brain tissue from the ventricular to the pial surface. The uptake of 131I-CSA in the brain of the hydrocephalic cats perfused for 4 hours was not related to perfusion pressure. However, the concentration attained after 1 hour of perfusion was higher in the animals perfused under high pressure. In the latter group the uptake after 1 hour was identifical to that found after 4 hours. This suggests that the perfusion pressure is important to increase the rate of flow of 131I-CSA (and fluid) through the extracellular spaces. The distance beyond the ventricular surface to which the perfusate penetrated before it was removed by the blood was 2.5–3 mm.

Cerebrospinal fluid production and histological observations in animals with experimental obstructive hydrocephalus

The effect of obstructive hydrocephalus on CSF formation in cats and dogs was studied. Experimental hydrocephalus resulted from the intracisternal injection of kaolin. The rate of formation of CSF was calculated from measurements made during stteady state lateral ventricle-to-lateral ventricle perfusion. Spinal fluid production in hydrocephalic cats was 0.0027 ml/min or approximately 20% of that found in normal cats during ventriculocisternal perfusion. In hydrocephalic dogs, the rate of CSF formation was 0.033 ml/min which was 0.014 ml/min less, or 70% than that reported for normal dogs. The marked reduction in CSF synthesis in the cat was attributed to the histological changes observed in the choroid plexus and ependymal lining of the ventricles. In addition, spongiform changes in the white matter of the brain were noted.

Changes in the Cerebrum Associated with Experimental Obstructive Hydrocephalus

Changes in the Cerebrum Associated with Experimental Obstructive Hydrocephalus