Highlights of Animal and In-Vitro Studies for TSC:

Hypoxia-related animal models show significant effects

• Hemorrhagic shock: improvement in survival
• Cardiovascular disease/stroke: reduced ischemic penumbra
• Respiratory disorders: enhanced PO2
• Oxygen enhancement in hyperoxic animals: allows study of TSC’s dose/response/duration of action

Radiation sensitization studies show significant effects

• Rat and mouse tumor models have been studied in conjunction with radiation therapy and TSC
• Numerous studies compare various doses of TSC with radiation therapy versus radiation therapy alone
• Significant improvements in survival, tumor shrinkage and tumor control seen

In vitro and in silico studies support the mechanism of action

• Demonstrate enhanced hydrogen bonding
• Demonstrate enhanced diffusion of both oxygen and glucose by about 30 percent
• Alternative mechanism hypotheses do not explain increased tissue oxygen consumption

Selected Published Research

Lapchak, P; Efficacy and Safety Profile of the Carotenoid Trans Sodium Crocetinate Administered to Rabbits Following Multiple Infarct Ischemic Strokes: A Combination Therapy Study with Tissue Plasminogen Activator. Brain Res. 2010;1309:136-145.

Sheehan J, Cifarelli CP, Dassoulas K, Olson C, Rainey J, Han S. Trans-sodium crocetinate enhancing survival and glioma response on magnetic resonance imaging to radiation and temozolomide. Journal of Neurosurgery. 2009 Dec 11. [Epub ahead of print]; Vol. 0, No. 0, Pages 1-6 (doi: 10.3171/2009.11.JNS091314). Journal of Neurosurgery. 2010; 1309: 234–239.

Manabe H, Okonkwo DO, Gainer JL, Clarke RH, Lee KS. Protection against focal ischemic injury to the brain by trans-sodium crocetinate. Journal of Neurosurgery. [Epub ahead of print] 2009; Vol. 0, No. 0, Pages 1-8 (doi: 10.3171/2009.10.JNS09562). Online Podcast

Sheehan, J, Sherman J, Cifarelli C, Jagannathan J, Dassoulas K, Olson C, Rainey J, Han S. Effect of trans sodium crocetinate on brain tumor oxgenation . Journal of Neurosurgery. 2009;111:226-229.

Sheehan J, Ionescu A, Pouratian N, Hamilton DK, Schlesinger D, Oskouian RJ, Sansur C. Use of trans sodium crocetinate for sensitizing glioblastoma multiforme to radiation. Journal of Neurosurgery. 2008: 108(5):972-97.

Stennett A, Murray R, Roy J, Gainer J. Trans-Sodium Crocetinate and Hemorrhagic Shock. Shock. 2007: 28(3):339-344.

Gainer J, Stennett A, Murray R. The Effect of Trans Sodium Crocetinate (TSC) in a Rat Oleic Acid Model of Acute Lung Injury. Pulmonary Pharmacology and Therapeutics. 2005;18:213-216.

Stennett A, Gainer J. TSC for Hemorrhagic Shock: Effects on Cytokines and Blood Pressure. Shock. 2004;22:569-574.

Okonkwo D, Wagner J, Melon D, et al. Trans-Sodium Crocetinate Increases Oxygen Delivery to Brain Parenchyma in Rats on Oxygen Supplementation. Neuroscience Letters. 2003;352:97-100.

Giassi L, Poynter A, Gainer J. Trans Sodium Crocetinate for Hemorrhagic Shock: Effect of Time Delay in Initiating Therapy. Shock. 2002;18(6):585-588.

Giassi L, Gainer J. TSC and Hemorrhagic Shock, A Review. Adv. Expt. Med. Biol. 2003;540:55-60.

Giassi L, Gilchrist M, Graham M, Gainer J. Trans Sodium Crocetinate Restores Blood Pressure, Heart Rate and Plasma Lactate after Hemorrhagic Shock. Journal of Trauma, Injury, Infection and Critical Care. 2001:51;932-938.

Singer M, Stidwill R, Nathan A, Gainer J. Intravenous Crocetinate Prolongs Survival in Lethal Hypoxemia. Critical Care Medicine. 2000;28:1968-1972.

Roy J, Graham M, Griffin A, Gainer J. A Novel Fluid Resuscitation Therapy for Hemorrhagic Shock. Shock. 1998;10:213-217.

Graham M, Gainer J. Increasing Oxygen Consumption and Survival with Fluid Resuscitation Therapy for Hemorrhagic Shock in Rats. Adv Exp Med Biol. 1997; 428:343-348.

Gainer J, Rudolph D, Caraway D. The Effect of Crocetin on Hemorrhagic Shock in Rats. Circulatory Shock. 1993;41:1-7.