Chronic intracerebroventricular administration is a reliable method in brain studies on monkeys

Abstract

Intracerebroventricular (ICV) administration through cannulas is a direct way to deliver large molecules and substances that are blocked by the blood-brain barrier into the central nervous system (CNS). It is widely used in brain studies on monkeys. However, this method is invasive, as it requires guide cannulas to be implanted into the brain. Whether the long-term implantation of the cannula and the administration of molecule-delivering vehicles, usually saline, can affect the brain by inducing chronic CNS inflammation or even worse brain atrophy, remains an issue to be solved. To answer this question, we investigated inflammatory markers and brain structures on three vehicle-control monkeys who received cannula implantation and one-year ICV saline administration in another study. During the experiment, the monkeys’ cerebrospinal fluid (CSF) samples were collected periodically, and the level of three classic inflammatory markers (IL-1β, IL-6, and TNF-α) were measured by electrochemiluminescence immunoassay. The monkeys’ brain structures were imaged in vivo periodically by 9.4 Tesla magnetic resonance imaging, which can provide the best-resolution magnetic resonance images of living monkeys, and the volume of the hippocampus was measured to evaluate the brain atrophy. The data reveal that, during the administrating period, the long-term levels of the inflammatory markers in the CSF and the volumes of the hippocampus did not change significantly compared with the baseline. These results suggest that the long-term ICV administration of saline through cannulas did not induce chronic neuroinflammation or brain atrophy in these rhesus monkeys, suggesting chronic ICV administration via implanted cannulas is a reliable method in monkey brain research.