Citation

Wali B, Stein D, Sayeed I. J. Neurotrauma 2017; 34(13): 2183-2186.

Affiliation

Emory University, Emergency Medicine, Atlanta, Georgia, United States ; isayeed@emory.edu.

Copyright

(Copyright © 2017, Mary Ann Liebert Publishers)

DOI

10.1089/neu.2016.4845

PMID

28075214

Abstract

The recent disappointing results of Phase 3 trials for progesterone (PROG) in traumatic brain injury (TBI) have triggered speculation about reasons for the negative outcomes. One confounding factor may have been the vehicle used to administer PROG. Virtually all of the many preclinical experiments informing the clinical trials and reporting beneficial PROG effects used more soluble 2-hydroxypropyl-b-cyclodextrin (HBC) as a vehicle given intraperitoneally or subcutaneously rather than a lipid formulation given intravenously (i.v.). The present investigation compared the effect of PROG infusion with that of lipid emulsion (Intralipid®) as a carrier/vehicle on edema following TBI in rats. Eight-mg/kg doses of PROG with 20% Intralipid were given i.v. via central venous catheter beginning 1h post-injury over a 1h duration (1.2 ml/hour). Animals were killed and brains removed at 24h post-injury. All the brain-injured groups showed more edema compared to the control group. However, PROG+Intralipid significantly attenuated cerebral swelling compared to Intralipid alone. No difference was observed between the TBI-alone and Intralipid groups. Although this study used much a smaller volume and shorter duration of Intralipid infusion than the clinical trials (up to 5 days of continuous infusion), our results suggest that the use of Intralipid in rats did not prevent or mask the beneficial effect of PROG.

Language: en

Keywords

Brain Edema; Rat; TRAUMATIC BRAIN INJURY