Traumatic brain injury (TBI) induces a spectrum of cerebrovascular dysfunction, ranging from impaired? pressure autoregulation which causes TBI patients to be more vulnerable to secondary ischemic insults to? severe global ischemia. Cerebral blood flow (CBF), especially within the first 12 hr after injury, is strongly? predictive of neurological outcome, with each 10ml/100g/min increase in cortical CBF resulting in a 3-fold? increase in the chances of surviving to hospital discharge. In past studies, a TBI management strategy that? maintained an increased cerebral perfusion pressure to prevent ischemia in patients with severe TBI was? very successful at reducing the incidence of jugular desaturation. However, when this management strategy? was applied to all patients with severe TBI, adverse effects (especially increased incidence of adult? respiratory distress syndrome) appeared to offset any beneficial effect on long-term outcome. Currently, we? are studying the role that testing of dynamic pressure autoregulation might play in identifying those patients? at greatest risk for developing ischemia and who might therefore benefit most from a hypertensive? management strategy. However, we have found that after severe TBI, almost all (87%) patients have? impaired dynamic pressure autoregulation. We now believe that any effective therapy directed at vascular? dysfunction will have to be applied to all patients with severe TBI.? Trauma is the most common cause of death in the 1-44 yr age group, and the third most common cause? for the entire US population. Trauma accounts for more loss of work life-years than cancer and? cardiovascular diseases combined. Effective treatments for this important public health disorder are needed.? Treatment of the cerebrovascular dysfunction caused by TBI could significantly improve neurological? recovery following trauma.? We propose to study the physiological effects of administration of recombinant human erythropoietin? (rhEpo), an agent that has been found to have potent neuroprotective effects after experimental TBI and? spinal cord injury and that has the added benefit of stimulating erythropoiesis in critically ill patients.? Preliminary data suggests that part of the mechanism of neuroprotection by rhEpo is likely to be amelioration? of cerebrovascular dysfunction, possibly through upregulation of endothelial nitric oxide synthase. The goals? of this project include the following: 1. To study the natural history of Epo and Epo receptor expression by? the injured brain; 2. To study the acute effects of rhEpo administration on cerebral hemodynamics; 3. To? study the chronic effects of rhEpo administration on the brain's response to injury.?

National Institute of Health (NIH)
National Institute of Neurological Disorders and Stroke (NINDS)
Research Program Projects (P01)
Project #
Application #
Study Section
National Institute of Neurological Disorders and Stroke Initial Review Group (NSD)
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Baylor College of Medicine
United States
Zip Code
Rubin, Maria Laura; Chan, Wenyaw; Yamal, Jose-Miguel et al. (2017) A joint logistic regression and covariate-adjusted continuous-time Markov chain model. Stat Med 36:4570-4582
Aisiku, Imoigele P; Yamal, Jose-Miguel; Doshi, Pratik et al. (2016) The incidence of ARDS and associated mortality in severe TBI using the Berlin definition. J Trauma Acute Care Surg 80:308-12
Aisiku, Imo P; Yamal, Jose-Miguel; Doshi, Pratik et al. (2016) Plasma cytokines IL-6, IL-8, and IL-10 are associated with the development of acute respiratory distress syndrome in patients with severe traumatic brain injury. Crit Care 20:288
Vedantam, Aditya; Yamal, Jose-Miguel; Rubin, Maria Laura et al. (2016) Progressive hemorrhagic injury after severe traumatic brain injury: effect of hemoglobin transfusion thresholds. J Neurosurg 125:1229-1234
Lazaridis, Christos; Yang, Ming; DeSantis, Stacia M et al. (2015) Predictors of intensive care unit length of stay and intracranial pressure in severe traumatic brain injury. J Crit Care 30:1258-62
Yamal, José-Miguel; Benoit, Julia S; Doshi, Pratik et al. (2015) Association of transfusion red blood cell storage age and blood oxygenation, long-term neurologic outcome, and mortality in traumatic brain injury. J Trauma Acute Care Surg 79:843-9
Yamal, Jose-Miguel; Rubin, M Laura; Benoit, Julia S et al. (2015) Effect of Hemoglobin Transfusion Threshold on Cerebral Hemodynamics and Oxygenation. J Neurotrauma 32:1239-45
Yamal, Jose-Miguel; Robertson, Claudia S; Rubin, M Laura et al. (2014) Enrollment of racially/ethnically diverse participants in traumatic brain injury trials: effect of availability of exception from informed consent. Clin Trials 11:187-94
Robertson, Claudia S; Yamal, Jose-Miguel; Tilley, Barbara C (2014) Erythropoietin for traumatic brain injury--reply. JAMA 312:1929
Robertson, Claudia S; Hannay, H Julia; Yamal, José-Miguel et al. (2014) Effect of erythropoietin and transfusion threshold on neurological recovery after traumatic brain injury: a randomized clinical trial. JAMA 312:36-47

Showing the most recent 10 out of 70 publications