Raised intracranial pressure increases CSF drainage through arachnoid villi and extracranial lymphatics

We demonstrated previously that about one-half of cerebrospinal fluid (CSF) removed from the cranial vault was cleared by extracranial lymphatic vessels. In this report we test the hypothesis that lymphatic drainage of CSF increases as intracranial pressure (ICP) is elevated in anesthetized sheep. Catheters were inserted into both lateral ventricles, cisterna magna, cervical lymphatics, and jugular vein. A ventriculocisternal perfusion system was employed to regulate CSF pressures and to deliver a protein tracer (125I-labeled human serum albumin) into the CSF compartment.131I-labeled human serum albumin was injected intravenously to permit calculation of plasma tracer loss and tracer recirculation into lymphatics. ICP was controlled by adjusting the height of the inflow reservoir and the cisterna magna outflow catheter appropriately. The experimental design consisted of a 3-h period of lower pressure followed by a 3-h period of higher pressure in the same animal (10–20 or 20–30 cmH2O). We determined that incremental changes in ICP were associated with higher CSF transport through lymphatic and arachnoid villi routes in all eight animals tested ( P = 0.004).

Cerebrospinal fluid formation and absorption in dehydrated sheep

Cerebrospinal fluid (CSF) plays an important role in the brain’s adaptive response to acute osmotic disturbances. In the present experiments, the effect of 48-h dehydration on CSF formation and absorption rates was studied in conscious adult sheep. Animals had cannulas chronically implanted into the lateral cerebral ventricles and cisterna magna to enable the ventriculocisternal perfusion. A 48-h water deprivation altered neither CSF production nor resistance to CSF absorption. However, in the water-depleted sheep, intraventricular pressure tended to be lower than that found under control conditions. This likely resulted from decreased extracellular fluid volume and a subsequent drop in central venous pressure occurring in dehydrated animals. In conclusion, our findings provide evidence for the maintenance of CSF production during mild dehydration, which may play a role in the regulation of fluid balance in the brain during chronic hyperosmotic stress.

Brain edema resolution by CSF pathways and brain vasculature in cats

Brain edema is a major contributor to the brain swelling process and raised intracranial pressure, yet the specific pathways involved in clearance of brain edema (fluid and proteins) and their relative contribution to the resolution process remain unknown. The objective of this study was to document the temporal course of edema resolution from brain to cerebrospinal fluid (CSF) and by the brain vasculature. Radioiodinated (125I) cat serum albumin (RICSA) was infused continuously into the white matter of anesthetized adult cats for 8 h, and ventriculocisternal perfusion was used to monitor the RICSA activity in CSF at 15-min intervals and to compare with the blood taken at 15-min intervals. The RICSA that cleared from the brain in 8 h measured 29.8% of the amount infused. Of the amount of RICSA leaving the brain, we found that the CSF compartment accounted for 87.14% of the cleared RICSA volume, while only 10.96% of RICSA was found in the blood during the 8-h experiment. The amount of RICSA remaining in the brain when the animal was killed equaled 71.2 +/- 15.9% (mean +/- SD) of the RICSA infused. We conclude that vascular clearance during the acute stage of resolution is minimal and that clearance of RICSA occurs predominantly via the CSF pathways.

Effect of Atriopeptin on Production of Cerebrospinal Fluid

We reported previously that intravenous infusion of atriopeptin increases blood flow to the choroid plexus. The first goal of this study was to determine whether blood-borne atriopeptin increases the production of CSF. Ventriculocisternal perfusion was used to measure the production of CSF in anesthetized rabbits. Atriopeptin increased blood flow to the choroid plexus (measured with microspheres) but did not alter the production of CSF. The second goal of the study was to determine whether intracerebroventricular injection of atriopeptin affects the production of CSF. Injection of atriopeptin into the cerebral ventricles increased blood flow to the choroid plexus but produced a small decrease in production of CSF. In summary, blood-borne and intraventricular atriopeptin increase blood flow to the choroid plexus, but do not increase the production of CSF.

Effect of vasopressin on production of cerebrospinal fluid: possible role of vasopressin (V1)-receptors

The goal of this study was to examine the role of arginine vasopressin in humoral regulation of choroid plexus function. Production of cerebrospinal fluid (CSF) was measured in anesthetized rabbits with an indicator dilution method, by using ventriculocisternal perfusion of artificial CSF containing blue dextran. Rabbits received either vehicle, vasopressin or vasopressin in the presence of the V1-antagonist [1-(beta-mercapto-beta,beta-cyclopentamethylene propionic acid), 2-(O-methyl)tyrosine]arginine vasopressin ([d(CH2)5Tyr(Me)]-AVP). Under control conditions, blood flow to the choroid plexus (measured with microspheres) averaged 369 +/- 26 (mean +/- SE) ml.min-1.100 g-1 and CSF production averaged 9.9 +/- 0.9 microliters/min. Intravenous infusion of vasopressin (2 mU.kg-1.min-1 for 90 min) decreased blood flow to the choroid plexus by 50-60% for the entire period of infusion. Vasopressin decreased production of CSF by 35 +/- 8%. Blood flow to the choroid plexus and production of CSF did not change significantly from control values in animals that received vehicle. In the presence of the V1-antagonist (10 micrograms/kg), infusion of vasopressin had no effect on blood flow to the choroid plexus or production of CSF. Thus circulating vasopressin, at plasma levels that are observed under physiological and pathophysiological conditions, has important effects on formation of CSF, as well as on blood flow to the choroid plexus. These findings are consistent with the hypothesis that effects of vasopressin on both variables are mediated through vasopressin (V1)-receptors.