Douglas Tadaki_ PhD _NMRC_ - Oak Ridge National Laboratory

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Session: 3
“Blast/Brain/Bone: Effect of blast on post injury complications”

                        Douglas Tadaki, PhD
                        Department of Regenerative Medicine
                        Naval Medical Research Center

                        Time/Date 1:00 – 2:15; 26 May 2010
                        Session: Brain Injuries and Neuro-Regeneration Panel

        Traumatic brain injury is the signature battlefield injury of Operation Iraqi Freedom
and Operation Enduring Freedom. Currently there are intense investigations into the effect
of blast and traumatic brain injury.     Our laboratory has focused on post injury sequelae
associated with to exposure to blast and traumatic brain injury.              One interesting
complication seen in combat wounded is heterotopic ossification (HO). HO is the formation
of mature lamellar bone in non-osseous tissues, can lead to disability due to ankylosis of
joints, neuropathy, ulceration and pain. Heterotopic ossification is commonly associated
with severe systemic insults such as spinal cord injury and traumatic brain injury, but can
also develop after hip arthroplasty and fractures of the acetabulum or elbow. Despite
significant recent progress, the underlying cause and inciting factors of HO formation remain
largely unknown.
        Following civilian trauma, HO is expected to form after 11% of traumatic brain
injuries and 21% of spinal cord injuries.      In patients with high-energy penetrating war
wounds, the prevalence of HO is significantly higher at 64%. Identified risk factors in these
patients include amputations within the zone of injury, injuries due to a blast, and patients
with an Injury Severity Score >16. Further investigation reveals associations between HO
and wound failure, bacterial colonization, and over-expression of pro-inflammatory
cytokines implicating a systemic inflammatory component.
        Interestingly, medications administered to this cohort may also provide clues to the
mechanism by which HO forms. Tricyclic antidepressants are commonly prescribed to treat
symptoms of neurogenic pain, traumatic brain injury and/or post-traumatic stress disorder.
Likewise, selective serotonin reuptake inhibitors (SSRIs), recently shown to inhibit bone
formation and remodeling, are used to treat a broad range of affective disorders in these
patients. We have identified a significant association between tricyclic antidepressants and
the incidence of heterotopic ossification.

Biographical Sketch:
Dr. Douglas Tadaki is currently the Chairman of the Department of Regenerative Medicine in
the Operational and Undersea Medicine Directorate of the Naval Medical Research Center.
Dr. Tadaki received his PhD in Biomedical Sciences from the University of Tennessee and
the Oak Ridge National Laboratories. He was commissioned as a Lieutenant in the U.S.
Navy, Medical Service Corp and was assigned to the Naval Medical Research Institute in
Bethesda. His work focused on the developing rodent models of autoimmunity. Dr. Tadaki
was then assigned to the National Institutes of Diabetes and Digestive and Kidney Diseases
(NIDDK) to study xenotransplantation and he conducted seminal studies in using antibody
therapy to prevent rejection in kidney transplants in non-human primates. Dr. Tadaki
returned to the Naval Medical Research Center to serve as the Program Head for the
Transplantation Program and as the Deputy Department Head for the Radiation and Combat
Injury Department. Dr. Tadaki is a member of numerous organizations including the
American Society of Transplantation (AST), American Society of Transplant Surgeons
(ASTS), and the International Society of Cell Therapy (ISCT). He has also been appointed
to the national working group on composite tissue transplantation for ASTS. His current
research interests include composite tissue transplantation and the role of mesenchymal
stem cells in wound healing.

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