Gerald M. Hochwald

Protective effect of transforming growth factor beta 1 on experimental autoimmune diseases in mice.

Interleukin 1 (IL-1) and tumor necrosis factor alpha are thought to contribute to the inflammatory response associated with autoimmune diseases. Transforming growth factor beta 1 (TGF-beta 1) counteracts many effects of these cytokines and has various immunosuppressive properties. In the present study, it is shown that microgram amounts of TGF-beta 1, injected daily for 1-2 weeks, protect against collagen-induced arthritis (CIA) and relapsing experimental allergic encephalomyelitis (REAE), the animal models for rheumatoid arthritis and multiple sclerosis, respectively. When administered during induction of the disease, TGF-beta 1 prevents CIA but only delays the onset of REAE by 2-3 days. However, when administered during a remission. TGF-beta 1 prevents the occurrence of relapses in REAE. The results suggest that TGF-beta 1 has powerful anti-inflammatory effects, mimicking in some respects the beneficial effects of immunosuppressive drugs in these experimental models of autoimmune disease, but without discernable adverse effects.

Evaluation of Pediatric Hydrocephalus by Computed Tomography

Computed tomography (CT) is a safe and reliable technique for the study of children with increased head circumference. Hydrocephalic children requiring drainage of cerebrospinal fluid may be shunted on the basis of the CT scan alone and their postsurgical course followed by serial CT scans thereafter. Any additional pneumographic studies required may be performed via the existing shunt tube, eliminating transcerebral catheterization and its attendant complications.

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

Abstract 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.

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 H2O) or low (≤0 cm H2O) 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.

Effects of changes in serum osmolarity on bulk flow of fluid into cerebral ventricles and on brain water content

SummaryThe effects of changes in serum osmolarity on the rate and osmolarity of bulk flow of fluid into the cerebral ventricles and on cortical white and grey matter water content were studied in cats. Bulk flow rates and osmolarities were measured during ventriculocisternal perfusion both before and after intravenous infusion of glucose solutions. Infusions of glucose in concentrations greater than 6% decreased fluid bulk flow rate and its osmolarity. Glucose in concentrations less than 6% increased fluid bulk flow rate and decreased its osmolarity. Bulk flow rate and serum osmolarity were found to be linearly related with a coefficient of osmotic flow of −0.835 μl/min per mOsm/l. At the extremes of induced serum osmolarities, (290 and 360 mOsm/l) bulk flow rate was either increased by 120% or completely inhibited. Effluent osmolarity also increased proportionately to serum osmolarity (0.338 mOsm/l per mOsm/l). When compared to controls, cortical grey and white matter water content increased by 1.9% and 2.9%, respectively, when the infused glucose concentration was 2.5% or less, and decreased by 1.8% and 2.9% when the concentration was 10% or more. The results of these experiments suggest that the increased bulk flow comes from the brain, rather then directly from the blood.

Experimental hydrocephalus: Cerebrospinal fluid formation and ventricular size as a function of intraventricular pressure

Abstract Cats with kaolin-induced obstructive hydrocephalus were studied by ventricle-to-ventricle perfusion in order to determine the influence of pressure on CSF formation and ventricular volume. It was demonstrated that in the individual hydrocephalic cat CSF production decreases as perfusion pressure is elevated. The mean decrease in CSF formation was found to be 3.5%/cm H 2 O pressure. It is proposed that this reduction is due to an adverse effect of intraventricular pressure on choroidal plexus, ependyma and adjacent brain tissue. Ventricular volume was shown to increase as rapidly as the pressure, at a rate of 0.0906 to 0.1031 ml/cm H 2 O pressure. This increase is to a large extent at the expense of the brain, and reversible within a short period of time. From pressure-dependent changes in ventricular volume it was possible to calculate the bulk elastic modulus of brain tissue. Its mean value was 3.848·10 5 dynes/cm 2 and most probably represents the elastic properties of the various components of brain tissue.

NEONATAL HYDROCEPHALUS TREATED BY COMPRESSIVE HEAD WRAPPING

Abstract A treatment is described for hydrocephalus, based on the premise that increasing the resistance to expansion of the skull by compressive bandaging promotes increased C.S.F. absorption, presumably by transventricular pathways.

Effect of spinal fluid pressure on cerebrospinal fluid formation

Abstract The effect of spinal fluid pressure on cerebrospinal fluid (CSF) formation was measured in rabbits and cats. A decreased rate of CSF production with increased perfusion pressure was found, which was best illustrated by paired comparisons in individual animals during ventriculocisternal perfusion at both low (−5 to −10 cm H2O) and high (20–25 cm H2O) perfusion pressure. Each animal was perfused at either pressure for 2 hr (rabbits) or 2.5 hr (cats) for steady-state measurements. After a gradual change in hydrostatic pressure, perfusion continued for an additional 1.5 hr (rabbits) or 2 hr (cats) when steady-state measurements were repeated. The mean rate of CSF production decreased in rabbits from 0.0081 to 0.0045 ml/min after the perfusion pressure was elevated. This effect was independent of whether the animals were perfused initially under high or low pressure. In cats, after a similar increase in perfusion pressure, the mean rate of CSF formation decreased from 0.0212 to 0.0102 ml/min.

Exchange of γ-globulin between blood, cerebrospinal fluid and brain in the cat

Abstract The exchange of γ-globulin between blood, brain, and cerebrospinal fluid was studied in cats during steady-state ventriculocisternal perfusion. The clearance of I 131 -labeled cat γ-globulin was dependent on bulk absorption of cerebrospinal fluid, and was independent of protein concentration (3 μg to 5 mg/ml). Less than 0.1% of the radioactivity could be recovered from the brain when I 131 -γ-globulin was added to the perfusion fluid. When I 131 -γ-globulin was injected intravenously the total amount of this protein entering the ventricular system was 0.7 μg/min. The ratio of specific activities of perfusate/serum approached unity between 4 and 24 hours after injection. The addition of acetazolamide resulted in a reduction of CSF formation, and decrease in influx and specific activity of γ-globulin in the perfusate. The transfer of γ-globulin from blood to cerebrospinal fluid is only partially dependent on bulk fluid formation by the choroid plexus; a portion of this protein probably enters from the surrounding nervous tissue. The results of these experiments and others on the exchange of albumin are compared, and the mechanism determining the total protein concentration in cerebrospinal fluid are discussed.

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 rôle 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.