8.14: Presentation session: Brain injuries and neuro-regeneration panel: “Blast/brain/bone: Effect of blast on post injury complications”

Abstract

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.