Early Intervention Therapy for Mild Blast Exposure Injury via a Whole-Brain Ultrasound Stimulation Device
Abstract
Detonations of improvised explosive devices have in recent years resulted in an unforeseen large number of injuries among US military personnel. Many Soldiers with blast injury suffer from brain trauma. While traumatic brain injury with frank tissue injury is well-described clinically, one of the unpleasant discoveries of the recent years has been the severity by which mild blast injury affects the psychological health of military Service personnel. A complex mixture of symptoms ranging from headache, fatigue, nausea, sleep disturbances, impaired judgement, concentration, and memory loss are observed in a subpopulation of individuals exposed to blast injury. A common view among researchers in the field of blast injury is that blood-brain barrier damage and toxic waste buildup in the brain are what may be causing Soldiers who have one or multiple mild-blast injuries to develop brain disorders in months to year after the injury. Toxic particle overaccumulation is also observed in subjects who have Alzheimer’s disease or related disorders. The healthy brain is protected by the blood-brain barrier, which prevents toxic waste from passing from blood to brain. However, when the brain is exposed to a blast wave from an explosion, the blood vessels start to act abnormally for several hour to days after the blast injury, letting toxic particles into the brain tissue and also permitting toxic waste buildup. This can be happening even though there is no external bleeding from the victim’s head and clinically the blast injury is more of a concussion-type injury. We predict that exposing the blast-injured brain to ultrasound treatment will help retighten the leak-blood vessels and at the same time help flush the toxic particles out the brain. As there is currently no treatment for mild blast-induced traumatic brain injury, our main objective is to build an ultrasound device capable of delivering ultrasound to a Soldier’s brain while they are in the military transport vehicle leaving the location of the explosion. The proposed device we will develop will look like a helmet, which can be placed on the victim’s head for 30 minutes of more after blast injury. We predict that ultrasound treatment will be most effective if performed within hours of the blast injury. We predict that ultrasound waves may help heal the brain after blast injury because studies have shown that ultrasound waves can be beneficial and (1) can help repair the blood-brain barrier when it is damaged and (2) can also (slightly) expand the fluid space surrounding brain cells, thereby increasing fluid circulation through the brain tissue and toxic waste drainage. Our research plan uses rodent animals that are exposed to a simulated blast trauma so we can test whether or not our device heals the animals’ brain. Magnetic resonance imaging (MRI) will be used to measure how or if the ultrasound restores the leaky blood-vessel back to normal. The imaging will also be used to visualize if the ultrasound treatment will increase fluid flow through the brain and waste drainage as we predict it will. Our proposed experiments will determine if the ultrasound treatment works properly on animals in the setting of blast injury before continuing to perform testing on humans with mild blast injuries or to rehabilitate others who have Alzheimer’s disease or the other related brain disorders.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Nov 19, 2019
- Source ID
- W81XWH1910749
Entities
People
- Spencer Brinker
Organizations
- United States Army
- Yale University