Contribution of extracranial lymphatics and arachnoid villi to the clearance of a CSF tracer in the rat

The objective of this study was to determine the relative roles of arachnoid villi and cervical lymphatics in the clearance of a cerebrospinal fluid (CSF) tracer in rats. I-125-labeled human serum albumin (I-125-HSA; 100 mu g) was injected into one lateral ventricle, and an Evans blue dye-rat protein complex was injected intravenously. Arterial blood was sampled for 3 h. Immediately after this, multiple cervical vessels were Ligated in the same animals, and plasma recoveries were monitored for a further 3 h after the intracerebroventricular injection of 100 mu g I-131-HSA. Tracer recovery in plasma at 3 h averaged (%injected dose) 0.697 +/- 0.042 before lymphatic ligation and dropped significantly to 0.357 +/- 0.060 after ligation. Estimates of the rate constant associated with the transport of the CSF tracer to plasma were also significantly lower after obstruction of cervical lymphatics (from 0.584 +/- 0.072/h to 0.217 +/- 0.056/h). No significant changes were observed in sham-operated animals. Assuming that the movement of the CSF tracer to plasma in lymph-ligated animals was a result of arachnoid villi clearance, we conclude that arachnoid villi and extracranial lymphatic pathways contributed equally to the clearance of the CSF tracer from the cranial vault.