Hydrocephalic Cats Research Articles

Preservation of functional architecture in visual cortex of cats with experimentally induced hydrocephalus

We investigated how neural function is preserved or matured in the visual cortex of cats, following the induction of hydrocephalus by kaolin injection. In vivo optical imaging of intrinsic signals in 11-17-week-old hydrocephalic cats revealed orientation maps showing the orderly arrangement of preferred orientations when stimulated by grating stimuli at a low spatial frequency, whereas stimulus-evoked intrinsic signals in response to gratings at a high spatial frequency were often too weak to construct orientation maps. Furthermore, in two of the three hydrocephalic cats, initially deteriorated orientation maps became almost regular maps in the second imaging experiments conducted 8 and 11 weeks, respectively, after the first imaging. This indicates that, despite large structural deformation of the hydrocephalic brain, orientation maps are elaborated sufficiently after the age of 5-6 months, by which time the orientation map formation is usually completed in normal cats. Single unit recording from the decompressed visual cortex revealed that many neurons showed normal orientation selectivity, whereas the binocularity of these neurons was found to be reduced. These results suggested that the deformed visual cortex of hydrocephalic cats exhibits a high plasticity, retaining its functional organization.

Acute and chronic cerebral white matter damage in neonatal hydrocephalus.

The neonatal cat model of kaolin-induced hydrocephalus is associated with progressive and severe ventriculomegaly. In this experiment we studied the evolution of the histopathological changes in hydrocephalic (n = 23) cats from 5-168 days after the induction of hydrocephalus along with age-matched controls (n = 10). In the periventricular white matter, extracellular edema and axonal damage were present within days of the onset of hydrocephalus. This was followed by reactive gliosis, white matter atrophy, and in some animals gross cavitation of the white matter. Even in the chronic, apparently compensated state there was ongoing glial cell death. Six cats were shunted an average of 23.6 +/- 6.5 days after the induction of hydrocephalus because they were no longer able to feed independently. In spite of clinical improvement the white matter changes persisted. Overt cortical changes were minimal except where areas of white matter destruction encroached upon the deep layers. The white matter changes are very similar to those seen in periventricular leukomalacia and suggest that ischemia plays a role in neonatal brain injury caused by hydrocephalus.

Hydrocephalus in developing cats: Physiological properties of visual cortex cells

Hydrocephalus in developing cats: Physiological properties of visual cortex cells

A laboratory model of shunt-dependent hydrocephalus. Development and biomechanical characterization.

This study was designed to determine whether implanting shunts in hydrocephalic cats produced the same biomechanical changes as have previously been found in children with shunts. Neuraxis volume-buffering capacity (pressure-volume index: PVI) and the resistance to the absorption of cerebrospinal fluid (CSF) were determined before and 3 weeks after placing shunts in 16 hydrocephalic cats. Intracranial pressure (ICP) was monitored for at least 6 hours after the shunts were occluded. The brains were perfused in vivo and removed to assess the size of the ventricles. The mean PVI of the hydrocephalic cats was 3.6 +/- 0.2 ml (+/- standard error of the mean) before the shunts were placed. Three weeks after adequate shunt function was first established, the mean PVI decreased to 1.1 +/- 0.1 ml and was similar to values determined in control animals. Prior to shunt placement, the resistance to the absorption of CSF was 28.4 +/- 4.5 mm Hg/ml/min and did not vary with ICP. This parameter changed after shunting and increased as a function of ICP (r = 0.87, p less than 0.001). At ICP's below 20 mm Hg, the resistance to the absorption of CSF was 65.0 +/- 18.0 mm Hg/ml/min but increased to 220.0 +/- 40.5 mm Hg/ml/min when determined at ICP's above 20 mm Hg. Corroborating evidence for this linkage of resistance to the absorption of CSF to ICP was found in the inexorable rise of ICP during the 6 hours of monitoring after the shunts were occluded. After shunt placement, the ventricles were normal in size in 12 cats and slightly enlarged in four. The biomechanical profile and pressure response to shunt occlusion in this laboratory model resembles that previously described in shunt-dependent children. As in humans, shunt placement in hydrocephalic cats results in normalization of the PVI and a linkage of the resistance to the absorption of CSF to ICP. The significance of these changes as they relate to shunt dependency is discussed.

Cerebral blood flow and metabolism in experimental hydrocephalus.

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

Effects of hydrocephalus and increased intracranial pressure on auditory and somatosensory evoked responses.

Recent studies in human and animal subjects have suggested a relationship between intracranial pressure (ICP) and ventricular dilatation and multimodality evoked responses which, if substantiated, would be of value to clinical practice as a noninvasive way of assessing the need for shunting in selected patients in whom computed tomography (CT) is not definitive. In an attempt to better define these changes, auditory evoked response (BAER) and somatosensory evoked response (SER) were performed on 16 cats as a base line, after which they were made hydrocephalic by the cisternal injection of kaolin. Nine cats survived, and CT or magnetic resonance scans were performed on them 4 to 6 weeks later. In those animals in which ventricular dilatation was noted, repeat evoked responses were recorded. In the 6 hydrocephalic cats, the ventricle was punctured to measure ICP, which in all cases was less then 5 mm Hg. The lumbar spinal dural sac was then ligated, which resulted in periodic plateau waves up to 75 to 100 mm Hg after 4 to 6 hours, lasting up to 10 minutes. In neither group of cats was any change in either BAER or SER observed until preterminally, when ICP was in the range of 75 to 100 mm HG and cerebral perfusion pressure was compromised. This suggests that the BAER and SER are not sensitive to either ventricular dilatation or intracranial hypertension.

Experimental feline hydrocephalus. The role of biomechanical changes in ventricular enlargement in cats.

In a craniectomy-durectomy model of kaolin-induced feline hydrocephalus, the pressure-volume index (PVI) technique of bolus manipulations of cerebrospinal fluid (CSF) was used to study the biomechanical changes associated with hydrocephalus. Steady-state intracranial pressure (ICP), PVI, and the resistance to the absorption of CSF were determined acutely and 3 to 5 weeks later in hydrocephalic cats and time-matched control cats. Steady-state ICP was 11.0 +/- 2.1 mm Hg (+/- standard deviation) in the hydrocephalic cats, compared to 10.8 +/- 2.2 mm Hg in the chronic control group (p greater than 0.1). The ICP in both the chronic hydrocephalic and chronic control groups was significantly higher (p less than 0.001) than after acute durectomy (mean ICP 8.5 +/- 1.2 mm Hg). Immediately after dural opening, the mean PVI was 3.6 +/- 0.2 ml (+/- standard error of the mean); over time, it decreased to 1.3 +/- 0.1 ml in the chronic control group (p less than 0.001), but remained elevated in the hydrocephalic group at 3.5 +/- 0.4 ml (p less than 0.001). Resistance to CSF absorption was 9.1 +/- 1.4 mm Hg/ml/min immediately after dural opening and increased to 28.8 +/- 4.5 mm Hg/ml/min (p less than 0.001) in the hydrocephalic cats; it increased even further in the chronic measurements in control cats, to 82.3 +/- 9.2 mm Hg/ml/min (p less than 0.001). Ventricular size was moderate to severely enlarged in all hydrocephalic cats, and normal in the control group. These results indicate that the biomechanical profile of the altered brain container model of kaolin-induced feline hydrocephalus resembles that described in hydrocephalic infants. As shown in the control subjects, an absorptive defect alone is not sufficient to cause progressive ventricular enlargement. Increased volume-buffering capacity coupled with a moderate increase of CSF absorption resistance facilitates volume storage in the ventricles.

Effects of arterial pco2 and cerebrospinal fluid volume flow rate changes on choroid plexus and cerebral blood flow in normal and experimental hydrocephalic cats.

The effect of changes in brain blood flow on cerebrospinal fluid (CSF) volume flow rates, and that of changes in CSF volume flow rates on brain blood flow were determined in both normal and kaolin-induced hydrocephalic cats. In both groups of cats, blood flow in grey and white matter, cerebral cortex, and choroid plexus was measured with 105Ru microspheres during normocapnia, and again with 141Ce microspheres after arterial Pco2 was either increased by 300% or decreased by 50%. Blood flow measurements were also made during perfusion of the ventricular system with mock CSF and repeated during perfusion with anisosmotic mannitol solutions to alter CSF volume flow rate. In 30 normal and 26 hydrocephalic cats, blood flow to the cerebral cortex, white matter, and choroid plexus was similar; only blood flow to the caudate nucleus was greater in normal cats. The weight of the choroid plexus from hydrocephalic cats decreased by 17%. Blood flow in the choroid plexus of all cats decreased by almost 50% following hypercapnia or hypocapnia, without a change in the CSF volume flow rate. There was no change in cerebral or choroidal blood flow when CSF volume flow rate was either increased by 170% or decreased by 80%. These results suggest that choroid plexus blood flow does not limit or affect the volume flow rate of CSF from the choroid plexus. CSF volume flow rate can be altered without corresponding blood flow changes of the brain or choroid plexus. Choroid plexus blood flow and the reactivity of both brain and choroidal blood flow to changes in arterial Pco2 were not affected by the hydrocephalus. The lower CSF formation rate of hydrocephalic cats can be attributed in part to the decrease in the mass of choroid plexus tissue.

Pressure-absorption responses to the infusion of fluid into the spinal cord central canal of kaolin-hydrocephalic cats.

The resistance to cerebrospinal fluid (CSF) absorption through the alternative CSF absorption pathway in kaolin-induced hydrocephalic cats was measured by the constant infusion-manometric test. The cerebral ventricles were bypassed, and artificial CSF was infused directly into the central canal of the spinal cord. The infusion rates were increased stepwise from 0.022 to 0.168 ml/min when the capacity to absorb CSF was exceeded. There was an initial increase in resistance which was associated with the emergence of infusion fluid through a slit-like opening in the dorsal columns of the lower lumbar spinal cord. The resistance to flow decreased when the infusion rate was greater than 0.086 ml/min. Fluid accumulated in the spinal subarachnoid space when the ability to absorb was exceeded. The diversion of this fluid caused the pressure in the spinal cord central canal to fall rapidly. The results suggest that the CSF absorption deficit in chronic kaolin-induced hydrocephalic cats is probably caused by the restriction of CSF flow from the central canal through the spinal cord and into the spinal subarachnoid space. As a result of kaolin, the central canal is sufficiently dilated to permit, during infusion, the flow of at least five times as much CSF as the hydrocephalic cats produce. It is not clear whether the overloading of the CSF absorption mechanism is due to the restrictions imposed by the size of the subarachnoid space, or to the structures in this space involved with the return of CSF to the blood.

A Comparison of Choroid Plexus and Cerebral Blood Flow in Normal and Experimental Hydrocephalic Cats

A Comparison of Choroid Plexus and Cerebral Blood Flow in Normal and Experimental Hydrocephalic Cats

Kaolin-induced hydrocephalus impairs CSF secretion by the choroid plexus.

CSF volume flow and sodium (Na+)-influx rates in normal and kaolin-induced hydrocephalic cats were measured during ventricular perfusion with anisotonic sucrose solutions. When ventricular fluid osmolality was 120 mOsm, CSF volume flow ceased for both groups of cats. As ventricular fluid osmolality was increased, the CSF volume flow rate of normal cats increased to 70 microliter per minute, and in hydrocephalic cats to 40 microliter per minute. In normal cats, for ventricular fluid osmolality between 50 and 350 mOsm, Na+-influx was constant and thought to occur by diffusion; while for higher osmolalities, Na+-influx increased. In hydrocephalic cats, Na+-influx increased over the entire range of ventricular osmolality but was less than in normal cats. Acetazolamide decreased the CSF volume flow in normal cats by 40 percent, but was ineffective in hydrocephalic cats. These results suggest that CSF secretion by the choroid plexus of cats with kaolin-induced hydrocephalus is impaired.

Sodium exchange between blood, brain, and CSF in normal and hydrocephalic cats.

The exchange of sodium between blood, brain, and cerebrospinal fluid was studied in normal and kaolin-induced hydrocephalic cats. The ventricles were perfused to measure fluid formation and Na+ exchange rates. 22Na was added to the perfusion fluid or injected intravenously as a tracer for Na+ movement. Na+ and 22Na were also measured in cortical gray and white matter. Na+ relative specific activities were calculated for brain, effluent fluid, and serum. With 22Na in the perfusion fluid, Na+ exchange was not different from nascent Na+ influx for both normal and hydrocephalic cats. Na+ relative specific activities of cortical gray and white matter were 10 times greater in hydrocephalic than in normal cats. This difference in Na+ relative specific activity for brain may be due to a higher diffusion constant or to a lower brain capillary permeability. When 22Na was given intravenously, the Na+ diffusional exchange for normal cats was less than that measured when 22Na+ was in the perfusion fluid. In hydrocephalic cats, the Na+ diffusional exchange was effectively zero. Na+ relative specific activities of cortical gray and white matter were the same for normal and hydrocephalic cats. These findings suggest that the impaired Na+ diffusional exchange may be due to pathological changes in the choroid plexus.

On the movement of fluid through the brain of hydrocephalie cats

The effects of changes in serum osmolality on the volume flow of fluid into the cerebral ventricles and on brain water content was examined in cats with kaolin-induced hydrocephalus. Slopes of the regression lines relating volume flow and serum osmolality for both normal and hydrocephalic cats are the same. The constant difference in flow rates between the two lines, 7 mul per minute, is probably due to impaired choroid plexuow rates between the two lines, 7 mul per minute, is probably due to impaired choroid plexus function of the hydrocephalic cats. The osmotic pressure gradient that causes the flow of fluid is therefore probably between blood and brain. Under these conditions changes in brain water content of hydrocephalic cats were smaller than in normals and can be related to the edema present in this disorder. Despite the inflammatory response to kaolin, the blood-brain barrier remains intact. From the calculated filtration coefficient, it can be inferred that the flow of water from serum through brain and into cerebrospinal fluid is limited by the resistance of fluid flow through the brain.

Interaction of ligandin with radiographic contrast media.

Ligandin (Y protein) is an abundant cytoplasmic glutathione transferase present in liver, kidney and gut in various animals and man. Its interaction with four radiologic contrast media (Telepaque, 3-(3 amino-2,4,6, triiodophenyl -2 ethylpropanoic acid, sodium salt; Hypaque, sodium -3, 5-diacetamido-2,4,6,-triiodobenzoate; Cholografin, N,N'adipyl-bis-(3-amino-2,4,6-triiodobenzoic acid) N-methyl-glucosamine; Diodrast, 3,5-Diiodo-4-pyridone-N-acetic acid, Diethanolamine Salt was investigated by observing inhibitory effects on the enzyme-catalyzed conjugation of glutathione with 1-chloro-2, 4-dinitrobenzene. Lineweaver-Burk plots of reciprocal initial velocity versus reciprocal inhibitor concentrations at fixed glutathione and chlorodinitrobenzene concentrations demonstrate non-competitive inhibition by all contrast media except Diodrast. No conjugates of contrast media with glutathione were formed. It is postulated that intracellular accumulation of contrast media is aided by intracellular binding with ligandin. Inhibition of the GSH transferase activity of ligandin can disrupt the mercapturate formation, an important detoxification process.

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.

Rhenium-188 therapy of experimental hydrocephalus

Rhenium-188 therapy of experimental hydrocephalus

Changes in regional blood-flow and water content of brain and spinal cord in acute and chronic experimental hydrocephalus.

The effects of kaolin-induced hydrocephalus on regional blood-flow and water content of cat brain and spinal cord were measured. The role of the central canal of the spinal cord as an alternative pathway for cerebrospinal fluid in experimental hydrocephalus was also studied by positive contrast ventriculography. In comparison with normal cats, blood-flow in the cerebrum, cerebellum and brain stem of cats with acute hydrocephalus was reduced by more than 20 per cent: in those with chronic hydrocephalus it was reduced by only 12 per cent. There was an absolute increase of 1-5 per cent in water content of the brain in cats with acute hydrocephalus. Water content in the spinal cord was increased by 6 per cent in cats with acute hydrocephalus and by 8 per cent in those with chronic hydrocephalus. When the increased water-content was taken into account, hydrocephalus caused no significant change in blood-flow in the cervical, thoracic or lumbar spinal cord. Contrast material perfused through the ventricles of hydrocephalic cats flowed directly into the enlarged central canal of the spinal cord. Kaolin-induced arachnoiditis completely obstructed communication between the ventricles and the cranial subarachnoid space. The contrast material in the central canal communicated both with the cavities extending into the dorsal columns and with the spinal subarachnoid space. When kaolin was injected directly into the spinal subarachnoid space there was an increase in spinal water-content, without an enlarged central canal. These results suggest that in addition to kaolin-induced arachnoiditis, increased intraluminal pressure is necessary to enlarge the central canal.

Cerebral fluid dynamics and brain regional blood flow in experimental hydrocephalus.

Cerebral blood flow was measured by the indicator fractionation technique in normal, acute hydrocephalic, chronic compensated hydrocephalic and craniectomized hydrocephalic cats. In the five normal cats the mean total brain blood flow was 136.1 ml/min/100 g dry weight. The six acute hydrocephalic animals demonstrated a relatively uniform 22% reduction in total blood flow. In eight chronic hydrocephalic cats CBF increased to the point where there was only an overall 7% decrease. In three hydrocephalic and craniectomized cats the CBF was reduced by 30.6%. In the acute phases there was a decrease in the number of blood vessels. Chronic compensated hydrocephalic brains had somewhat more vessels than the normal, whereas the craniectomized, massively hydrocephalic brain had a dramatic increase in both the number and caliber of blood vessels. These results clearly demonstrate that in acute obstructive hydrocephalus in cats, there is a significant decrease in CBF. The blood vessels revert to normal in shunted cats.

Radioisotope ventriculography in cats with kaolin-induced hydrocephalus.

Movement of radioisotope from the ventricles in normal and kaolin-hydrocephalic cats was studied with a gamma camera. In hydrocephalic cats there was a progression of activity down the spinal axis reaching the region of the filum terminale within 20 minutes. Systemic absorption, assessed by appearance of activity in regions of the bladder and flank, was delayed when compared with normal cats. This delay corresponded to the time for the radioisotope to travel the length of the spine. This route of flow in hydrocephalic cats was shown by dye perfusion to be via the central canal and filum terminale to the spinal subarachnoid space. Other studies on kaolin-hydrocephalic cats proposing absorption of cerebrospinal fluid by the brain should be reconsidered.

Cerebrospinal fluid resistance and compliance in subacutely hydrocephalic cats.

The use of CSF resistance determinations as a diagnostic test for acute hydrocephalus appears feasible. Resistance and compliance of the CSF circulation were measured in 25 cats. Kaolin then was infused into the cisterna magna of 20 of these cats and artificial CSF into the cisterna magna of the other five. Repeat resistance and compliance measurements were made on each cat at a predetermined time within a month after the cisternal infusion. The animal was then killed, the brain fixed, and the degree of hydrocephalus estimated from measurements made on lateral ventricles in coronal section. Progressive hydrocephalus developed only in the kaolin-treated cats. Resistance was increased and compliance was normal in the hydrocephalic cats. Resistance decreased as the duration of hydrocephalus increased, implying that progressive hydrocephalus could not be explained by inadequate CSF absorption alone.