Blood samples will be drawn on traumatic brain injury patients who are participating in the ProTECT III study just prior to the initiation of the study drug infusion and 24 and 48 hours from the time they are enrolled in the study to test for biomarkers that may help predict how severe the injury is and how well they improve. The investigators will also test to see if the study medication is being absorbed and is staying at a consistent level in the blood stream.
Inclusion Criteria: - Moderate to severe brain injury (iGCS 12-4 or motor response 2-5 if intubated). - Age >18 years (or developmental stage Tanner 5 in patients where age is not known) - Blunt, traumatic, closed head injury (altered mental status due to brain injury) - Able to initiate study drug infusion within 4 hours from time of injury - Exclusion Criteria: - Non-survivable injury as determined by treating - Bilateral dilated unresponsive pupils - Spinal cord injury with neurological deficits, pre-injury paralysis (quad/paraplegic) - Inability to perform activities of daily living (ADL) without assistance - Cardiopulmonary arrest - Status epilepticus on arrival or concern for post ictal state - systolic blood pressure < 90 for two consecutive readings at least 5 minutes apart any time prior to randomization - O2 Sat < 90 for at least 5 consecutive minutes any time prior to randomization - Prisoner or ward of state - Known active breast or reproductive organ cancers (via medical records or family interview) - Known allergy to progesterone or Intralipid components (egg yolk) (via medical records or family interview) - Known history of blood clotting disorder (Protein S or C deficiency, etc.) or history of pulmonary embolism (via medical records or family interview) or active/ongoing thromboembolic event (myocardial infarction, ischemic stroke, pulmonary embolism, deep vein thrombosis). - Blood or serum ethanol (EtOH) ≥ 250 mg % - Positive qualitative urine or serum pregnancy test - Concern for inability to follow up at 6 months (residence in foreign country, homeless with limited contacts, - undocumented immigrants, or high likelihood of becoming incarcerated during study period, etc.) - Patient in Opt Out registry or wearing Opt Out bracelet -