Cerebrovascular Reactivity Assessed With fNIRS as a Biomarker of TCVI After Acute Traumatic Brain Injury in Military

Summary

The study includes people who have recently had a traumatic brain injury (TBI) and healthy controls who have not had a TBI and is designed to measure brain blood flow serially after a TBI. Studies have shown that small blood vessels in the brain may be injured during a TBI. The goal is to learn about brain blood vessel function from as early as the first week to 6 months after a TBI . The study uses Near Infrared Spectroscopy (NIRS) which uses small lights that detect oxygen levels in the blood, measuring blood flow in the brain. This is compared with magnetic resonance imaging (MRI). When blood flow increases in the brain in response to a stimulus, this is called cerebral vascular reactivity (CVR). The study aims to learn about CVR using a few minutes of special breathing similar to breath holding while in an MRI (magnetic resonance imaging), and CVR measures after one dose of a common drug called sildenafil (generic Viagra) 50 mg taken once during CVR measurements at each of up to 4 visits. The investigators will measure CVR at different times during a 6-month period in participants who have had a TBI to see how CVR measures and blood vessels function during the first 6 months after a brain injury.

Timeline

Start

2019-08-09

Primary completion

2020-03-01

Completion

2020-03-01

Publications

• Results Hoge CW, McGurk D, Thomas JL, Cox AL, Engel CC, Castro CA. Mild traumatic brain injury in U.S. Soldiers returning from Iraq. N Engl J Med. 2008 Jan 31;358(5):453-63. doi: 10.1056/NEJMoa072972. Epub 2008 Jan 30.
• Results Washington CW, Derdeyn CP, Dhar R, Arias EJ, Chicoine MR, Cross DT, Dacey RG Jr, Han BH, Moran CJ, Rich KM, Vellimana AK, Zipfel GJ. A Phase I proof-of-concept and safety trial of sildenafil to treat cerebral vasospasm following subarachnoid hemorrhage. J Neurosurg. 2016 Feb;124(2):318-27. doi: 10.3171/2015.2.JNS142752. Epub 2015 Aug 28.
• Results Nicolakakis N, Aboulkassim T, Aliaga A, Tong XK, Rosa-Neto P, Hamel E. Intact memory in TGF-beta1 transgenic mice featuring chronic cerebrovascular deficit: recovery with pioglitazone. J Cereb Blood Flow Metab. 2011 Jan;31(1):200-11. doi: 10.1038/jcbfm.2010.78. Epub 2010 Jun 23.
• Results Nicolakakis N, Hamel E. Neurovascular function in Alzheimer's disease patients and experimental models. J Cereb Blood Flow Metab. 2011 Jun;31(6):1354-70. doi: 10.1038/jcbfm.2011.43. Epub 2011 Apr 6.
• Results Amyot F, Kenney K, Moore C, Haber M, Turtzo LC, Shenouda C, Silverman E, Gong Y, Qu BX, Harburg L, Lu HY, Wassermann EM, Diaz-Arrastia R. Imaging of Cerebrovascular Function in Chronic Traumatic Brain Injury. J Neurotrauma. 2018 May 15;35(10):1116-1123. doi: 10.1089/neu.2017.5114. Epub 2018 Mar 20.
• Results Zhang R, Wang Y, Zhang L, Zhang Z, Tsang W, Lu M, Zhang L, Chopp M. Sildenafil (Viagra) induces neurogenesis and promotes functional recovery after stroke in rats. Stroke. 2002 Nov;33(11):2675-80. doi: 10.1161/01.str.0000034399.95249.59.
• Results Li L, Jiang Q, Zhang L, Ding G, Gang Zhang Z, Li Q, Ewing JR, Lu M, Panda S, Ledbetter KA, Whitton PA, Chopp M. Angiogenesis and improved cerebral blood flow in the ischemic boundary area detected by MRI after administration of sildenafil to rats with embolic stroke. Brain Res. 2007 Feb 9;1132(1):185-92. doi: 10.1016/j.brainres.2006.10.098. Epub 2006 Dec 26.
• Results Ding G, Jiang Q, Li L, Zhang L, Zhang ZG, Ledbetter KA, Panda S, Davarani SP, Athiraman H, Li Q, Ewing JR, Chopp M. Magnetic resonance imaging investigation of axonal remodeling and angiogenesis after embolic stroke in sildenafil-treated rats. J Cereb Blood Flow Metab. 2008 Aug;28(8):1440-8. doi: 10.1038/jcbfm.2008.33. Epub 2008 Apr 16.
• Results Atalay B, Caner H, Cekinmez M, Ozen O, Celasun B, Altinors N. Systemic administration of phosphodiesterase V inhibitor, sildenafil citrate, for attenuation of cerebral vasospasm after experimental subarachnoid hemorrhage. Neurosurgery. 2006 Nov;59(5):1102-7; discussion 1107-8. doi: 10.1227/01.NEU.0000245605.22817.44.

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