Brain stem penetration by horseradish peroxidase from the cerebrospinal fluid spaces in the cat

Horseradish peroxidase (HRP) was used as an extracellular marker to determine the nature and time course of molecular penetration from the CSF into the brain stem parenchyma. Anesthetized cats were injected with HRP (1 or 2%) intracerebroventricularly or intracisternally. The brain was fixed in situ by vascular or ventriculocisternal perfusion with formaldehyde after 5 min to 24 h of exposure to HRP in the cerebrospinal fluid. After intraventricular injection, the widest band of penetration by HRP occurred in 5 min beneath the pial surface with radial spurs extending farther inward along perivascular and perineural sheaths. Permeation of the ependymal surface was more limited and uniform in depth even after 0.5 h. Clearing of the parenchyma was well advanced by 4 h and was essentially complete by 24 h with the exception of HRP contained in macrophages primarily along blood vessels. After intracisternal injection, distant labeling by HRP was found in the vascular endothelium of the upper brain stem parenchyma. We conclude that rapid and deep molecular penetration of the brain stem occurs from the subarachoid fluid space. Hence, effects of drugs in the cerebrospinal fluid attributed to activation of hypothetical chemoreceptors on the pial surface may actually result from actions upon structures deep in the parenchyma.