Traumatic Brain Injury

Background

EarlyStages keyTraumatic brain injury (TBI) occurs when the normal function of the brain is disturbed by either a closed or penetrating head injury. Injuries may be caused by focal impacts, sudden acceleration/deceleration within the cranium, or a combination of both. Focal impacts occur when the brain comes in contact with an object or with the inner surface of the skull, causing bruised brain tissue and hematomas. Acceleration/deceleration injuries involve shearing and straining forces and often tear blood vessels in the brain, leading to epidural and subdural hematoma, and/or in diffuse axonal injury (shearing of axons and microvasculature within the brain).

The most common causes of TBI are motor vehicle accidents, falls, violence, and sports-related injuries. Symptoms of TBI can include headache, blurred vision, nausea/vomiting, decreased consciousness, cognitive or neurological deficits, and skull fracture. Common disabilities include problems with cognition (memory, reasoning), sensory processing, communication, and personality/emotional functioning (depression, aggression, anxiety, distractibility). However, the majority of TBI’s are mild and resolve within 3 weeks, without producing long-term disability.

TBI affects approximately 1.6 million Americans per year and over 5.3 million people currently suffer from disabilities related to TBI.  

Current Treatment

Initial management consists of maintaining adequate ventilation, oxygenation, circulation, brain perfusion, and controlling raised intracranial pressure (ICP). Treatment varies based on the severity of the injury and is divided into medical management and surgical approaches.

TBI patients may receive skull and neck X-rays to check for bone fractures or spinal instability and/or be monitored with CT neuroimaging. In moderate to severe TBI, a head CT scan is used to monitor injury. Severely injured patients may require emergent intubation, mechanical ventilation, and measures to decrease elevated ICP including osmotic agents or surgery. Rehabilitation therapy (physical, speech, psychology) may also be recommended.

Focused Ultrasound

Focused Ultrasound is currently being researched in pre-clinical studies for the treatment of traumatic brain injury. A group with the U.S Food and Drug Administration is investigating the potential of FUS-induced neuromodulation (stimulating or blocking neural activity) to study the effects of blast-induced TBI and possibly treat the effects of TBI, including disruption of the blood-brain barrier, inflammation, immune responses, behavioral disturbances, and sleep disorders. In addition, Stem cell therapy is a promising strategy for the treatment of neurodegenerative diseases, including chronic TBI, in which there is neuroinflammation and neuronal cell death. FUS coupled with the injection of microbubbles can then be used to disrupt the blood-brain barrier for the non-invasive delivery of stem cells to the brain.

Notable Papers

McCutcheon V, Park E, Liu E, Sobhe Bidari P, Tavakkoli J, Wen XY, Baker AJ. A novel model of traumatic brain injury in adult zebrafish demonstrates response to injury and treatment comparable with mammalian models. J Neurotrauma. 2016 Sep 20.

Neren D, Johnson MD, Legon W, Bachour SP, Ling G, Divani AA. Vagus Nerve Stimulation and Other Neuromodulation Methods for Treatment of Traumatic Brain Injury. Neurocrit Care. 2016 Apr;24(2):308-19. doi: 10.1007/s12028-015-0203-0.

Fisher J, Huang S, Ye M, Nabili M, Wilent W, Krauthamer V, Myers M, Welle C. Real-Time Detection and Monitoring of Acute Brain Injury Utilizing Evoked Electroencephalographic Potentials. IEEE Trans Neural Syst Rehabil Eng. 2016 Mar 1.

Suarez MW, Dever DD, Gu X, Ray Illian P, McClintic AM, Mehic E, Mourad PD. Transcranial vibro-acoustography can detect traumatic brain injury, in-vivo: Preliminary studies. Ultrasonics. 2015 Aug;61:151-6. doi: 10.1016/j.ultras.2015.04.014.

Zibly Z, Graves CA, Harnof S, Hadani M, Cohen ZR. Sonoablation and application of MRI guided focused ultrasound in a preclinical model. J Clin Neurosci. 2014 Oct;21(10):1808-14.

Y.-S. Tung, F. Vlachos, J. A. Feshitan, M. A. Borden, and E. E. Konofagou, The mechanism of interaction between focused ultrasound and microbubbles in blood-brain barrier opening in mice. J. Acoust. Soc. Am., vol. 130, no. 5, pp. 3059–3067, Nov. 2011.

Burgess A, Ayala-Grosso CA, Ganguly M, Jordão JF, Aubert I, Hynynen K. Targeted delivery of neural stem cells to the brain using MRI-guided focused ultrasound to disrupt the blood-brain barrier. PLoS One. 2011;6(11)

     

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