{"id":241,"date":"2020-10-02T14:53:21","date_gmt":"2020-10-02T18:53:21","guid":{"rendered":"http:\/\/site.caes.uga.edu\/tnrrl\/?page_id=241"},"modified":"2026-06-09T21:26:22","modified_gmt":"2026-06-10T01:26:22","slug":"traumatic-brain-injury","status":"publish","type":"page","link":"https:\/\/site.caes.uga.edu\/tnrrl\/preclinical-research\/traumatic-brain-injury\/","title":{"rendered":"Traumatic Brain Injury"},"content":{"rendered":"\n<div class=\"wp-block-columns is-layout-flex wp-container-core-columns-is-layout-28f84493 wp-block-columns-is-layout-flex\">\n<div class=\"wp-block-column is-layout-flow wp-block-column-is-layout-flow\">\n<p style=\"font-size:clamp(14px, 0.875rem + ((1vw - 3.2px) * 0.385), 17px);px\">Traumatic brain injury (TBI) is a universal health concern as it is has been identified as a \u201csilent epidemic\u201d in civilians and the \u201csignature injury\u201d in U.S. service members (Soldiers) in the Iraq and Afghanistan wars<sup>1,2<\/sup>. Each year in America, 2.53 million civilians visit the emergency department after suffering a TBI, of which 56,800 die and over 288,000 require hospitalization and long term supportive care<sup>3<\/sup>. In addition, 400,000 TBI diagnoses have been confirmed in the Operation Enduring Freedom and Operation Iraqi Freedom conflicts<sup>4<\/sup>. 80% of these Soldiers will experience comorbid psychiatric diagnoses and are &gt;1.5x more likely to die from suicide than Soldiers without TBI<sup>5,6<\/sup>.&nbsp;These statistics correspond to civilian research where TBI has also been linked to suicide as well as mood and anxiety disorders<sup>7,8<\/sup>. Collectively, these consequences have major repercussions for TBI patients\u2019 families with psychological, emotional, and financial effects.<\/p>\n<\/div>\n\n\n\n<div class=\"wp-block-column is-layout-flow wp-block-column-is-layout-flow\">\n<figure class=\"wp-block-image size-large is-style-default\"><img loading=\"lazy\" decoding=\"async\" width=\"1016\" height=\"624\" src=\"https:\/\/site.caes.uga.edu\/tnrrl\/files\/2020\/11\/IMG_1322-3.jpg\" alt=\"\" class=\"wp-image-651\" srcset=\"https:\/\/site.caes.uga.edu\/tnrrl\/files\/2020\/11\/IMG_1322-3.jpg 1016w, https:\/\/site.caes.uga.edu\/tnrrl\/files\/2020\/11\/IMG_1322-3-300x184.jpg 300w, https:\/\/site.caes.uga.edu\/tnrrl\/files\/2020\/11\/IMG_1322-3-768x472.jpg 768w\" sizes=\"auto, (max-width: 1016px) 100vw, 1016px\" \/><figcaption class=\"wp-element-caption\"><em>Due to the prevalent use of improvised explosive devices, nearly 400,000 TBI diagnoses have been confirmed in the<\/em> <em>Iraq and Afghanistan conflicts. <\/em>A<em> TBI therapy that is accessible to Soldiers in combat zones is sorely needed. Photo courtesy of Michael Mahnken.<\/em><\/figcaption><\/figure>\n<\/div>\n<\/div>\n\n\n\n<p style=\"font-size:clamp(14px, 0.875rem + ((1vw - 3.2px) * 0.385), 17px);px\">Presently, there are no neuroprotective or regenerative Food and Drug Administration (FDA)-approved TBI treatments. TBI pathologies including brain swelling and intracerebral hemorrhage are often treated with hyperosmolar fluids, decompressive craniectomy, and surgical evacuation, all of which are associated with multiple risk factors<sup>9<\/sup>. Consequently, a safe and neuroprotective TBI treatment is sorely needed. Preclinical evaluation of novel therapies in our TBI pig model<sup>10-13<\/sup> is likely more predictive of human responses and outcomes due to the anatomical similarities between humans and pigs including brain size, gyrencephalic cytoarchitecture, and high white-to-gray matter ratios. These characteristics should be considered when evaluating the efficacy of novel therapeutics as they have a significant impact on TBI pathologies (e.g. cell death, excitotoxicity, inflammatory responses, intracerebral hemorrhage, and edema) and recovery mechanisms<sup>14,15<\/sup><em>.<\/em> <\/p>\n\n\n\n<div class=\"wp-block-columns is-layout-flex wp-container-core-columns-is-layout-28f84493 wp-block-columns-is-layout-flex\">\n<div class=\"wp-block-column is-layout-flow wp-block-column-is-layout-flow\">\n<ul class=\"wp-block-list\">\n<li>Brain size is critically important in modeling TBI as smaller rodent brains can tolerate much greater angular acceleration forces than animals with larger brains as shearing forces and inertial loading are directly related to brain mass<sup>16<\/sup>.<\/li>\n\n\n\n<li>Humans and pigs also have gyrencephalic brains, while rodents have lissencephalic brains. Gyrification significantly influences the movement of the brain within the cranium during TBI, as well as the maximum mechanical stress applied to neural tissues<sup>16<\/sup>.<\/li>\n\n\n\n<li>Human and pig brains are also composed of large white matter volumes (&gt;60%), compared to rodents (&lt;12%)<sup>17,18<\/sup>. White matter composition is important when modeling TBI as white matter is more susceptible than gray matter as it possesses 3-5x less microvasculature and limited collateralization<sup>19-21<\/sup>.<\/li>\n<\/ul>\n<\/div>\n\n\n\n<div class=\"wp-block-column is-layout-flow wp-block-column-is-layout-flow\">\n<figure class=\"wp-block-image size-large is-style-default\"><img loading=\"lazy\" decoding=\"async\" width=\"667\" height=\"389\" src=\"https:\/\/site.caes.uga.edu\/tnrrl\/files\/2020\/11\/TBIMri-7.png\" alt=\"\" class=\"wp-image-652\" srcset=\"https:\/\/site.caes.uga.edu\/tnrrl\/files\/2020\/11\/TBIMri-7.png 667w, https:\/\/site.caes.uga.edu\/tnrrl\/files\/2020\/11\/TBIMri-7-300x175.png 300w\" sizes=\"auto, (max-width: 667px) 100vw, 667px\" \/><figcaption class=\"wp-element-caption\"><em>MRI reveals post-TBI tissue (left) and white matter (right) damage in pigs closely mirrored that which is seen in humans. This is likely due to the inherent anatomical and physiological <em>similarities<\/em><\/em> <em>in brain composition and structure. Image courtesy of Dr. Kaiser.<\/em><\/figcaption><\/figure>\n<\/div>\n<\/div>\n\n\n\n<p style=\"font-size:clamp(14px, 0.875rem + ((1vw - 3.2px) * 0.385), 17px);px\">We believe our pig TBI model could serve as a translational platform for studying TBI sequelae across injury severities and identifying novel therapeutics.<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li><sup>1<\/sup><a rel=\"noreferrer noopener\" href=\"https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC4023660\/\" data-type=\"URL\" data-id=\"https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC4023660\/\" target=\"_blank\">Meaney, D.F., B. Morrison, and C. Dale Bass, <em>The mechanics of traumatic brain injury: a review of what we know and what we need to know for reducing its societal burden.<\/em> J Biomech Eng, 2014. <strong>136<\/strong>(2): p. 021008<\/a>.<\/li>\n\n\n\n<li><sup>2<\/sup><a rel=\"noreferrer noopener\" href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/22228249\/\" data-type=\"URL\" data-id=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/22228249\/\" target=\"_blank\">Taylor, B.C., et al., <em>Prevalence and costs of co-occurring traumatic brain injury with and without psychiatric disturbance and pain among Afghanistan and Iraq War Veteran V.A. users.<\/em> Med Care, 2012. <strong>50<\/strong>(4): p. 342-6.<\/a><\/li>\n\n\n\n<li><sup>3<\/sup><a rel=\"noreferrer noopener\" href=\"https:\/\/www.cdc.gov\/traumaticbraininjury\/get_the_facts.html\" data-type=\"URL\" data-id=\"https:\/\/www.cdc.gov\/traumaticbraininjury\/get_the_facts.html\" target=\"_blank\">Centers for Disease Control and Prevention (2019). Surveillance Report of Traumatic Brain Injury-related Emergency Department Visits, Hospitalizations, and Deaths\u2014United States, 2014. Centers for Disease Control and Prevention, U.S. Department of Health and Human Services<\/a>.<\/li>\n\n\n\n<li><sup>4<\/sup><a rel=\"noreferrer noopener\" href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/24810487\/\" data-type=\"URL\" data-id=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/24810487\/\" target=\"_blank\">Chase, R.P. and R.L. Nevin, <em>Population estimates of undocumented incident traumatic brain injuries among combat-deployed US military personnel.<\/em> J Head Trauma Rehabil, 2015. <strong>30<\/strong>(1): p. E57-64.<\/a><\/li>\n\n\n\n<li><sup>5<\/sup><a rel=\"noreferrer noopener\" href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/20127725\/\" data-type=\"URL\" data-id=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/20127725\/\" target=\"_blank\">Carlson, K.F., et al., <em>Psychiatric diagnoses among Iraq and Afghanistan war veterans screened for deployment-related traumatic brain injury.<\/em> J Trauma Stress, 2010. <strong>23<\/strong>(1): p. 17-24.<\/a><\/li>\n\n\n\n<li><sup>6<\/sup><a rel=\"noreferrer noopener\" href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/21734509\/\" data-type=\"URL\" data-id=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/21734509\/\" target=\"_blank\">Brenner, L.A., R.V. Ignacio, and F.C. Blow, <em>Suicide and traumatic brain injury among individuals seeking Veterans Health Administration services.<\/em> J Head Trauma Rehabil, 2011. <strong>26<\/strong>(4): p. 257-64.<\/a><\/li>\n\n\n\n<li><sup>7<\/sup><a rel=\"noreferrer noopener\" href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/26729611\/\" data-type=\"URL\" data-id=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/26729611\/\" target=\"_blank\">Scholten, A.C., et al., <em>Prevalence of and Risk Factors for Anxiety and Depressive Disorders after Traumatic Brain Injury: A Systematic Review.<\/em> J Neurotrauma, 2016. <strong>33<\/strong>(22): p. 1969-1994.<\/a><\/li>\n\n\n\n<li><sup>8<\/sup><a rel=\"noreferrer noopener\" href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/11689092\/\" data-type=\"URL\" data-id=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/11689092\/\" target=\"_blank\">Silver, J.M., et al., <em>The association between head injuries and psychiatric disorders: findings from the New Haven NIMH Epidemiologic Catchment Area Study.<\/em> Brain Inj, 2001. <strong>15<\/strong>(11): p. 935-45.<\/a><\/li>\n\n\n\n<li><sup>9<\/sup><a rel=\"noreferrer noopener\" href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/29764704\/\" data-type=\"URL\" data-id=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/29764704\/\" target=\"_blank\">Xiong, Y., A. Mahmood, and M. Chopp, <em>Current understanding of neuroinflammation after traumatic brain injury and cell-based therapeutic opportunities.<\/em> Chin J Traumatol, 2018. <strong>21<\/strong>(3): p. 137-151. 46<\/a>.&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; <\/li>\n\n\n\n<li><sup>10<\/sup><a rel=\"noreferrer noopener\" href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/30379914\/\" data-type=\"URL\" data-id=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/30379914\/\" target=\"_blank\">Baker, E.W., et al., <em>Scaled traumatic brain injury results in unique metabolomic signatures between gray matter, white matter, and serum in a piglet model.<\/em> PLoS One, 2018. <strong>13<\/strong>(10): p. e0206481<\/a>.<\/li>\n\n\n\n<li><sup>11<\/sup><a rel=\"noreferrer noopener\" href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/31084386\/\" data-type=\"URL\" data-id=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/31084386\/\" target=\"_blank\">Kinder, H.A., et al., <em>Traumatic Brain Injury Results in Dynamic Brain Structure Changes Leading to Acute and Chronic Motor Function Deficits in a Pediatric Piglet Model.<\/em> J Neurotrauma, 2019. <strong>36<\/strong>(20): p. 2930-2942<\/a>.<\/li>\n\n\n\n<li><sup>12<\/sup><a rel=\"noreferrer noopener\" href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/29916303\/\" data-type=\"URL\" data-id=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/29916303\/\" target=\"_blank\">Baker, E.W., et al., <em>Controlled Cortical Impact Severity Results in Graded Cellular, Tissue, and Functional Responses in a Piglet Traumatic Brain Injury Model.<\/em> J Neurotrauma, 2019. <strong>36<\/strong>(1): p. 61-73<\/a>.<\/li>\n\n\n\n<li><sup>13<\/sup><a rel=\"noreferrer noopener\" href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/31084390\/\" data-type=\"URL\" data-id=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/31084390\/\" target=\"_blank\">Kinder, H.A., et al., <em>Controlled Cortical Impact Leads to Cognitive and Motor Function Deficits that Correspond to Cellular Pathology in a Piglet Traumatic Brain Injury Model.<\/em> J Neurotrauma, 2019. <strong>36<\/strong>(19): p. 2810-2826<\/a>.<\/li>\n\n\n\n<li><sup>14<\/sup><a rel=\"noreferrer noopener\" href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/18256269\/\" data-type=\"URL\" data-id=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/18256269\/\" target=\"_blank\">Baltan, S., et al., <em>White matter vulnerability to ischemic injury increases with age because of enhanced excitotoxicity.<\/em> J Neurosci, 2008. <strong>28<\/strong>(6): p. 1479-89<\/a>.<\/li>\n\n\n\n<li><sup>15<\/sup><a rel=\"noreferrer noopener\" href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/19286576\/\" target=\"_blank\" data-type=\"URL\" data-id=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/19286576\/\">Jordan, L.C., J.T. Kleinman, and A.E. Hillis, <em>Intracerebral hemorrhage volume predicts poor neurologic outcome in children.<\/em> Stroke, 2009. <strong>40<\/strong>(5): p. 1666-71<\/a>.<\/li>\n\n\n\n<li><sup>16<\/sup><a rel=\"noreferrer noopener\" href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/28500771\/\" target=\"_blank\">Vink, R., <em>Large animal models of traumatic brain injury.<\/em> J Neurosci Res, 2018. <strong>96<\/strong>(4): p. 527-535.<\/a><\/li>\n\n\n\n<li><sup>17<\/sup><a rel=\"noreferrer noopener\" href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/12578225\/\" target=\"_blank\" data-type=\"URL\" data-id=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/12578225\/\">Tanaka, S.C., B.W. Balleine, and J.P. O&#8217;Doherty, <em>Calculating consequences: brain systems that encode the causal effects of actions.<\/em> J Neurosci, 2008. <strong>28<\/strong>(26): p. 6750-5<\/a>.<\/li>\n\n\n\n<li><sup>18<\/sup><a rel=\"noreferrer noopener\" href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/19485733\/\" data-type=\"URL\" data-id=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/19485733\/\" target=\"_blank\">Nakamura, M., et al., <em>Experimental investigation of encephalomyosynangiosis using gyrencephalic brain of the miniature pig: histopathological evaluation of dynamic reconstruction of vessels for functional anastomosis. Laboratory investigation.<\/em> J Neurosurg Pediatr, 2009. <strong>3<\/strong>(6): p. 488-95<\/a>.<\/li>\n\n\n\n<li><sup>19<\/sup><a rel=\"noreferrer noopener\" href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/2551935\/\" data-type=\"URL\" data-id=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/2551935\/\" target=\"_blank\">Borowsky, I.W. and R.C. Collins, <em>Metabolic anatomy of brain: a comparison of regional capillary density, glucose metabolism, and enzyme activities.<\/em> J Comp Neurol, 1989. <strong>288<\/strong>(3): p. 401-13<\/a>. <\/li>\n\n\n\n<li><sup>20<\/sup><a rel=\"noreferrer noopener\" href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/12578225\/\" data-type=\"URL\" data-id=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/12578225\/\" target=\"_blank\">Nonaka, H., et al., <em>The microvasculature of the cerebral white matter: arteries of the subcortical white matter.<\/em> J Neuropathol Exp Neurol, 2003. <strong>62<\/strong>(2): p. 154-61<\/a>.<\/li>\n\n\n\n<li><sup>21<\/sup><a rel=\"noreferrer noopener\" href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/15115733\/\" data-type=\"URL\" data-id=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/15115733\/\" target=\"_blank\">Peters, A. and C. Sethares, <em>Oligodendrocytes, their progenitors and other neuroglial cells in the aging primate cerebral cortex.<\/em> Cereb Cortex, 2004. <strong>14<\/strong>(9): p. 995-1007<\/a>.<\/li>\n<\/ul>\n","protected":false},"excerpt":{"rendered":"<p>Traumatic brain injury (TBI) is a universal health concern as it is has been identified as a \u201csilent epidemic\u201d in civilians and the \u201csignature injury\u201d in U.S. service members (Soldiers) in the Iraq and Afghanistan wars1,2. Each year in America, 2.53 million civilians visit the emergency department after suffering a TBI, of which 56,800 die [&hellip;]<\/p>\n","protected":false},"author":722,"featured_media":0,"parent":14,"menu_order":0,"comment_status":"closed","ping_status":"closed","template":"","meta":{"caes_section_patterns":[],"footnotes":""},"class_list":["post-241","page","type-page","status-publish","hentry"],"_links":{"self":[{"href":"https:\/\/site.caes.uga.edu\/tnrrl\/wp-json\/wp\/v2\/pages\/241","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/site.caes.uga.edu\/tnrrl\/wp-json\/wp\/v2\/pages"}],"about":[{"href":"https:\/\/site.caes.uga.edu\/tnrrl\/wp-json\/wp\/v2\/types\/page"}],"author":[{"embeddable":true,"href":"https:\/\/site.caes.uga.edu\/tnrrl\/wp-json\/wp\/v2\/users\/722"}],"replies":[{"embeddable":true,"href":"https:\/\/site.caes.uga.edu\/tnrrl\/wp-json\/wp\/v2\/comments?post=241"}],"version-history":[{"count":10,"href":"https:\/\/site.caes.uga.edu\/tnrrl\/wp-json\/wp\/v2\/pages\/241\/revisions"}],"predecessor-version":[{"id":1162,"href":"https:\/\/site.caes.uga.edu\/tnrrl\/wp-json\/wp\/v2\/pages\/241\/revisions\/1162"}],"up":[{"embeddable":true,"href":"https:\/\/site.caes.uga.edu\/tnrrl\/wp-json\/wp\/v2\/pages\/14"}],"wp:attachment":[{"href":"https:\/\/site.caes.uga.edu\/tnrrl\/wp-json\/wp\/v2\/media?parent=241"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}