We aim to develop a new therapeutic technique to improve therapeutic distribution throughout the central nervous system to treat disease.

Artificial cerebrospinal fluid (aCSF) was prepared at a stock concentration of 10x. The stock solution was then diluted down to 4x and 2x. 5% Hydrazide (Thermo Fisher) was mixed with aCSF at a 1:1 ratio to yield a final concentration of [2x] 2.5% hydrazide and [1x] 2.5% hydrazide.

Female, wild type C57 albino mice were anesthetized with 2.5% isoflurane. After ensuring adequate anesthetic depth, animals received a 10uL infusion of either 1x aCSF (n=2) or 2x aCSF (n=3) for a duration of 30-50 seconds. Animals were imaged using IVIS at 5-minute timepoints for 2 hours. Following imaging, animals underwent transcardial perfusion with 30mL of 1% heparinized saline and 4% paraformaldehyde (PFA). Brains and spinal cords were collected and placed in 4% PFA.

Mice who received hyperosmolar aCSF had increased fluorescent signal within the cranial vault on IVIS imaging. Ex vivo analysis revealed enhanced fluorescence within deep brain structures. Localization of hydrazide within the cortical white matter and olfactory bulbs were also more pronounced in mice receiving hyperosmolar aCSF. There was no difference in movement of hydrazide from the brain to spinal cord region of interest as assessed by IVIS imaging, suggesting that the primary impact of CFE on hydrazide was to influence its movement into deep parenchymal targets.