Traumatic Brain Injury in Veterans and Near-Infrared Phototherapy

Overview

This is a proof-of-concept study designed to demonstrate whether increases in cerebral blood flow, improvements in brain functioning, and reductions in symptomology associated with traumatic brain injury (TBI) can result from treatments consisting of near-infrared phototherapy (NIR).

The incidence of traumatic brain injury is widespread. The Centers for Disease Control estimate that 1.7 million TBIs occur each year and that TBI is a contributing factor in about 30% of all injury-related deaths. In addition, about 75% of these TBIs are concussions, or mild TBIs (mTBI). However, such concussions, especially multiple concussions that occur over time, are not harmless. The damage of even mild TBI can potentially lead to neuropsychiatric sequelae. Moreover, injury to the brain can worsen over time depending on the degree of inflammatory response and the areas of injury. TBI induces a number of neuropathological changes like aggregation of beta amyloid and tau proteins along with neuroinflammatory changes that resemble the pathology of degenerative diseases. For many of our returning Veterans, improvised explosive devices (IEDs) have been the cause of these TBIs. For example, data from the Defense Manpower Data Center indicates that as of October 3, 2011, explosive devices have been responsible for an estimated two-thirds or more of the battlefield injuries in Iraq; of the 46,532 warriors wounded in Operations Enduring Freedom and Iraqi Freedom, 30,347 were wounded by explosive devices, many of which were IEDs. Most of these injuries involved concussive brain injury. While current estimates are that 15-19% of all returning Warfighters have a history of acute concussion or TBI during their tour(s) of duty. It has been noted that "22.8% of a Brigade Combat Team returned from Iraq with confirmed deployment-acquired traumatic brain injury." Currently, there are no effective treatments for reversing or reducing the brain damage following TBI. Confounding the situation further, the symptoms of TBI can often overlap with those of post-traumatic stress disorder (PTSD) such as headache, dizziness, irritability, memory impairment, delayed problem solving, slowed reaction time, fatigue, visual disturbances, sleep disturbances, sensitivity to light and noise, impulsivity, judgment problems, emotional outbursts, depression, and anxiety. In addition, the rates of depression, anxiety, and other psychological symptoms are markedly elevated in TBI survivors, based on studies involving large samples of patients. As a result of this complexity and overlap of symptoms between TBI, PTSD, and depression, a clear diagnosis of TBI can be challenging, which can lead to misdirected treatment efforts and hamper the ability to accurately assess treatment response. Multiple published research studies have validated the healing mechanisms of NIR, which can be delivered via light-emitting diodes (LED). NIR phototherapy has been used extensively for wound healing of soft tissue, for increasing circulation, for the treatment of pain and for specific conditions such as hair growth and carpal tunnel syndrome. The mechanism of action that is central to the healing effect of NIR is increased blood circulation via the release of nitric oxide from red blood cells. Local increases in nitric oxide increase blood flow through arteries, veins and lymphatic ducts. Increased return of flow from treated sites helps to diminish intracellular acidosis that could alter mitochondrial membrane potential(s). This hypothesis holds that when blood flow is adequate, it provides a sufficient amount of oxygen and glucose to cells for adenosine triphosphate (ATP) generation by mitochondria. However, even a modest decrease in regional or global blood flow in the brain, such as that seen in TBI, will limit the amount of glucose and oxygen delivered to neurons. Restoring blood flow levels in damaged regions of the brain thus restores the necessary levels of glucose and oxygen required for ATP generation and proper neuronal functioning. In addition, nitric oxide stimulates angiogenesis and increased numbers of capillaries will aid in increasing blood flow (and oxygen and glucose) in injured areas of the brain where blood flow was subnormal. This effect contributes to enhanced mitochondrial function. The 1998 Nobel Prize for physiology was awarded to Furchgott, Ignarroand, and Murad for their discovery that nitric oxide acts as a signaling molecule and activates an enzyme, guanylate cyclase (GC), which is necessary for subsequent vasodilation. Finally, nitric oxide is an effective analgesic; it appears to reduce pain either by reversing local ischemia or directly in a manner akin to the analgesic effect of morphine. In the latter case, nitric oxide helps to regulate membrane potential via alterations in the activity of the ATP dependent potassium channel. This effect may be mediated by activated GC and subsequent phosphorylation of the potassium channel. Due to its capacity to non-invasively penetrate the skull, NIR has been safely used since the late 1970s for the determination of cerebral blood flow and oxygen levels in brain injured adults, post-stroke patients, and in pediatric patients. Furthermore, transcranial NIR has been shown to increase cortical perfusion and is associated with clinical improvement in human subjects with traumatic brain injury, neurodegenerative disease, and depression. The NIR device for this study is FDA cleared (510K; K101894) for increasing circulation and reducing pain.

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