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3 Understanding Pathophysiological Changes
Pages 31-52

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From page 31...
... Both the cascade of secondary effects and the longterm effects are consequences of the primary insult and are susceptible to interventions to improve resilience or to treat TBI. The chapter also includes a brief review of the animal models and biomarkers used for TBI.
From page 32...
... The weight-drop, midline fluid percussion, and controlled cortical impact models produce focal contusions and, depending on injury severity, may be associated with subarachnoid and intraparenchymal hemorrhages, STATIC MECHANICAL FORCE • Crushing INDIRECT Amplitude DYNAMIC Duration • Blast (explosion) wave-induced neurotrauma Velocity Acceleration DIRECT NON-IMPACT HEAD IMPACT ACCELERATION Head Motion PENETRATING INJURY / NON-PENETRATING INJURY / CONSTRAINED UNCONSTRAINED DIRECT BRAIN DEFORMATION IMPACT ACCELERATION • Miniature Swine • Primates Head Motion Head Motion • Rabbits • Rats CONSTRAINED UNCONSTRAINED CONSTRAINED UNCONSTRAINED • L ateral Fluid • High-Velocity • Controlled • Primate Impact Acceleration Percussion Missile Injury Concussion Models • Controlled Cortical • Weight-Drop Models • Ovine Impact Model Impact *
From page 33...
... impact acceleration model, (C) controlled cortical impact model, and (D)
From page 34...
... report Gulf War and Health: Volume 7: Long-Term Consequences of Traumatic Brain Injury, which describes the biology of TBI based on animal models and brain-injured patients and from other reviews (Cederberg and Siesjo, 2010; Margulies et al., 2009; Morganti-Kossmann et al., 2007, 2010; Unterberg et al., 2004; Werner and Engelhard, 2007; Ziebell and Morganti-Kossmann, 2010)
From page 35...
... The release of neurotransmitters, specifically glutamate, into the extracellular compartment results in an overstimulation of glutamate receptors linked to ion channels and creates prolonged membrane depolarization, depletion of ATP stores, and an increase in intracellular calcium derived from both extracellular and intracellular stores, indicating disturbances in mitochondrial function. (For a discussion of the timing of the cascade typically seen in experimental brain injury models and the consequences of the early, high glycolytic rate resulting in ionic pump disturbance, the reader
From page 36...
... , elevated lactate Physiologic disturbances: decreased Cytoskeletal changes in cell somas and cerebral blood flow, hypotension, axons hypoxemia, increased cranial pressure, decreased cerebral perfusion pressure Increased free radical production Widespread changes in gene expression: cell cycle, metabolism, inflammation, receptors, channels and transporters, signal transduction, cytoskeleton, membrane proteins involved in transcription/ translation Disruption of calcium homeostasis Inflammation: Cytokines, chemokines, cell adhesion molecules, influx of leukocytes, activation of resident macrophages Mitochondrial disturbances SOURCE: Margulies and Hicks, 2009. is referred to Hovda et al., 1995.)
From page 37...
... after TBI results in cytoskeletal damage, death of glia and neurons, and white matter degeneration. The two types of cell death that have been most studied are necrosis (due to mechanical or hypoxic tissue damage)
From page 38...
... . Although the newest imaging may suggest brain damage after mild traumatic brain injury (mTBI)
From page 39...
... Many growth factors (e.g., bFGF, NGF, BDNF,
From page 40...
... It is induced in cultured neurons and astrocytes under hypoxic and ischemic conditions, and it has been shown to have neuroprotective properties in various animal models of brain injury. Sex hormones (i.e., estrogen and progesterone)
From page 41...
... of reduced levels of VEGF in animal models. VEGF has been shown to be neuroprotective after experimental TBI models (Thau-Zuchman et al., 2010)
From page 42...
... . Mild TBI is difficult to model because the insults, whether produced by fluid percussion, cortical impact, or focal brain contusions, often generate focal damage, diffuse axonal damage, cell loss, and varying degrees of hemorrhage.
From page 43...
... . DoD's Policy Guidance for Management of Concussion/ Mild Traumatic Brain Injury in the Deployed Setting was updated in June 2010, and the 2008 Zurich Consensus Statement on Concussion in Sports (McCrory et al., 2009)
From page 44...
... There is some evidence for a temporal window of TABLE 3-6 Examples of Experimental Models of Repetitive TBI Species/Strain/ Experimental Model Experimental Design Age/Sex General Findings Concussion weight- 1 or 4 mild injuries each Mice/B6C3/ No overt cell death or evidence of disruption drop (closed head separated by 24 hours. 9 weeks old/ of the barrier in any groups.
From page 45...
... . Postmortem studies of athletes have suggested that repetitive head injury is associated with chronic traumatic encephalopathy (CTE)
From page 46...
... . To better understand and determine the role of blast as a mechanism of injury, 75 experts from the Department of Defense, the Department of Transportation, the Department of Veterans Affairs, academia, and industry were gathered from five countries in May 2009 to evaluate evidence from past and ongoing blast research at the International State-of-the-Science Meeting on Non-Impact, Blast-Induced Mild Traumatic Brain Injury.
From page 47...
... Development of animal models is particularly urgent for concussion/mild TBI and brain injuries because of blast as well as
From page 48...
... 2010. Traumatic brain injury, posttraumatic stress disorder, and postconcussion symptom reporting among troops returning from Iraq.
From page 49...
... 2010. A prospective diffusion tensor imaging study in mild traumatic brain injury.
From page 50...
... 2010. Animal models of traumatic brain injury: Is there an opti mal model to reproduce human brain injury in the laboratory?
From page 51...
... 2010. Vitamin E protects against oxidative damage and learning dis ability after mild traumatic brain injury in rats.


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