Targeting the brain with Curcumin: Can we treat Chronic Traumatic Encephalopathy?

Methods

Summary

We plan to administer Texas-Red labeled CLR-TargoSphere with encapsulated Curcumin 50 mg/kg sc daily to group #10: 10 healthy BALB/c female mice for 14 days. Dosing volume= 10 mL/kg (0.200 mL/20g mouse) and adjust volume accordingly for body weight. Control  Group #1: 10 healthy BALB/c female mice receive Test Article A= CLR-TargoSphere encapsulated mock substance.

All animals monitored individually and by body weight biwk. Any animal with single observation of > than 30% body weight loss or three corrective measurements of >25% body weight loss will be euthanized. Any weight loss of >20% will stop dosing. If loss is recovered within 10% of original weight, dosing may resume at lower dose or less frequent schedule. Exceptions may be allowed on a case-by-case basis.

Animals are euthanized per Charles River labs SOP#687.

If vehicle submitted by client is not one that has been previously used,  Study Director will submit protocol to IACUC for approval.

Timepoint: day 15, All animals Group #10 euthanized 

Organ Collection:

Brain: preservation; fix for 24hrs at room temperature in 4% formaldehyde made up in phosphate-buffered saline pH7.2 -7.4 (not critical, but within the physiological range). Shipping condition-room temperature. send to AUB attention U. of Arizona, Dr. William A. Day, Ph.D. for Anti-Texas Red Rabbit Ig , Goat anti-rabbit IG, blocking Solution, BSA-c, and embedding materials for slide preparation.; sectioning, and Transmission Electron Microscopy. TBD: Brain localization of TargoSphere labeled with Texas Red; Cellular localization of Texas Red and Curcumin.

IACUC  approval by Charles River Discovery Services:

October 13, 2017

Charles River Discovery Services-NC (CR DS-NC) Animal Care and Use Committee

Amendment to Animal Study Protocol #980701: Evaluation of Novel Compounds in Tumor Growth Delay Assay.

 Dr. Scolaro,

The CR DS-NC Animal Care and Use Committee has approved the expedited review of the following amendments to the animal study proposal indicated above.

•         CT26-e428

Expedited approval indicates that these amendments meet institutional requirements in the handling and care of experimental animals. As Principal Investigator, you are responsible for ensuring that studies are conducted in accordance with Public Health Service and CR DS-NC policies and guidelines.

Shawndel Arneson  IACUC Chair

Challenges

Charles River Labs has extensive experience in animal research and has a wide range of scientists and technicians to care and treat the animals in this study. Thus, we anticipate no adverse events.

We have worked previously with Dr. Day for TEM study of nanocarrier delivery to the brains of normal LEW rats, performed without issues or problems due to extensive experience in his areas of expertise.

Pre Analysis Plan

Findings will be analyzed at each institution by the Project Director, with statistical analyses and reports.