Large animal models of traumatic brain injury

2017 ◽  
Vol 96 (4) ◽  
pp. 527-535 ◽  
Author(s):  
Robert Vink
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Animal Models ◽  
Large Animal ◽  
Large Animal Models

scholarly journals Large animal models of stroke and traumatic brain injury as translational tools

2018 ◽  
Vol 315 (2) ◽  
pp. R165-R190 ◽  
Author(s):  
Annabel J. Sorby-Adams ◽  
Robert Vink ◽  
Renée J. Turner
Keyword(s):  
Traumatic Brain Injury ◽  
Ischemic Stroke ◽  
Brain Injury ◽  
Animal Models ◽  
Animal Species ◽  
Experimental Models ◽  
Clinical Translation ◽  
Large Animal ◽  
Large Animal Models ◽  
Significant Burden

Acute central nervous system injury, encompassing traumatic brain injury (TBI) and stroke, accounts for a significant burden of morbidity and mortality worldwide. Studies in animal models have greatly enhanced our understanding of the complex pathophysiology that underlies TBI and stroke and enabled the preclinical screening of over 1,000 novel therapeutic agents. Despite this, the translation of novel therapeutics from experimental models to clinical therapies has been extremely poor. One potential explanation for this poor clinical translation is the choice of experimental model, given that the majority of preclinical TBI and ischemic stroke studies have been conducted in small animals, such as rodents, which have small lissencephalic brains. However, the use of large animal species such as nonhuman primates, sheep, and pigs, which have large gyrencephalic human-like brains, may provide an avenue to improve clinical translation due to similarities in neuroanatomical structure when compared with widely adopted rodent models. This purpose of this review is to provide an overview of large animal models of TBI and ischemic stroke, including the surgical considerations, key benefits, and limitations of each approach.

scholarly journals A systematic review of large animal models of combined traumatic brain injury and hemorrhagic shock

2019 ◽  
Vol 104 ◽  
pp. 160-177 ◽  
Author(s):  
Andrew R. Mayer ◽  
Andrew B. Dodd ◽  
Meghan S. Vermillion ◽  
David D. Stephenson ◽  
Irshad H. Chaudry ◽  
...  
Keyword(s):  
Systematic Review ◽  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Animal Models ◽  
Hemorrhagic Shock ◽  
Large Animal ◽  
Large Animal Models

scholarly journals Reproducibility and Characterization of Head Kinematics During a Large Animal Acceleration Model of Traumatic Brain Injury

2021 ◽  
Vol 12 ◽  
Author(s):  
Andrew R. Mayer ◽  
Josef M. Ling ◽  
Andrew B. Dodd ◽  
Julie G. Rannou-Latella ◽  
David D. Stephenson ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Animal Models ◽  
Angular Velocity ◽  
Diffuse Axonal Injury ◽  
Impulsive Loading ◽  
Large Animal ◽  
Head Kinematics ◽  
Large Animal Models ◽  
Acceleration Model

Acceleration parameters have been utilized for the last six decades to investigate pathology in both human and animal models of traumatic brain injury (TBI), design safety equipment, and develop injury thresholds. Previous large animal models have quantified acceleration from impulsive loading forces (i.e., machine/object kinematics) rather than directly measuring head kinematics. No study has evaluated the reproducibility of head kinematics in large animal models. Nine (five males) sexually mature Yucatan swine were exposed to head rotation at a targeted peak angular velocity of 250 rad/s in the coronal plane. The results indicated that the measured peak angular velocity of the skull was 51% of the impulsive load, was experienced over 91% longer duration, and was multi- rather than uni-planar. These findings were replicated in a second experiment with a smaller cohort (N = 4). The reproducibility of skull kinematics data was mostly within acceptable ranges based on published industry standards, although the coefficients of variation (8.9% for peak angular velocity or 12.3% for duration) were higher than the impulsive loading parameters produced by the machine (1.1 vs. 2.5%, respectively). Immunohistochemical markers of diffuse axonal injury and blood–brain barrier breach were not associated with variation in either skull or machine kinematics, suggesting that the observed levels of variance in skull kinematics may not be biologically meaningful with the current sample sizes. The findings highlight the reproducibility of a large animal acceleration model of TBI and the importance of direct measurements of skull kinematics to determine the magnitude of angular velocity, refine injury criteria, and determine critical thresholds.

Large animal models of traumatic brain injury

2017 ◽  
Vol 128 (3) ◽  
pp. 243-254 ◽  
Author(s):  
Jun-Xi Dai ◽  
Yan-Bin Ma ◽  
Nan-Yang Le ◽  
Jun Cao ◽  
Yang Wang
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Animal Models ◽  
Large Animal ◽  
Large Animal Models

scholarly journals Perinatal hypoxic-ischemic brain injury in large animal models: Relevance to human neonatal encephalopathy

2018 ◽  
Vol 38 (12) ◽  
pp. 2092-2111 ◽  
Author(s):  
Raymond C Koehler ◽  
Zeng-Jin Yang ◽  
Jennifer K Lee ◽  
Lee J Martin
Keyword(s):  
Brain Injury ◽  
Animal Models ◽  
Cerebral Hypoperfusion ◽  
Large Animal ◽  
Perinatal Hypoxia ◽  
Cellular Mechanisms ◽  
Fetal Sheep ◽  
Newborn Piglets ◽  
Large Animal Models ◽  
Hypoxia Ischemia

Perinatal hypoxia-ischemia resulting in death or lifelong disabilities remains a major clinical disorder. Neonatal models of hypoxia-ischemia in rodents have enhanced our understanding of cellular mechanisms of neural injury in developing brain, but have limitations in simulating the range, accuracy, and physiology of clinical hypoxia-ischemia and the relevant systems neuropathology that contribute to the human brain injury pattern. Large animal models of perinatal hypoxia-ischemia, such as partial or complete asphyxia at the time of delivery of fetal monkeys, umbilical cord occlusion and cerebral hypoperfusion at different stages of gestation in fetal sheep, and severe hypoxia and hypoperfusion in newborn piglets, have largely overcome these limitations. In monkey, complete asphyxia produces preferential injury to cerebellum and primary sensory nuclei in brainstem and thalamus, whereas partial asphyxia produces preferential injury to somatosensory and motor cortex, basal ganglia, and thalamus. Mid-gestational fetal sheep provide a valuable model for studying vulnerability of progenitor oligodendrocytes. Hypoxia followed by asphyxia in newborn piglets replicates the systems injury seen in term newborns. Efficacy of post-insult hypothermia in animal models led to the success of clinical trials in term human neonates. Large animal models are now being used to explore adjunct therapy to augment hypothermic neuroprotection.

scholarly journals Respiratory Support of the Preterm Neonate: Lessons About Ventilation-Induced Brain Injury From Large Animal Models

2020 ◽  
Vol 11 ◽  
Author(s):  
Kyra Y. Y. Chan ◽  
Suzanne L. Miller ◽  
Georg M. Schmölzer ◽  
Vanesa Stojanovska ◽  
Graeme R. Polglase
Keyword(s):  
Brain Injury ◽  
Animal Models ◽  
Preterm Neonate ◽  
Respiratory Support ◽  
Large Animal ◽  
Large Animal Models

Parallel Human and Animal Models of Blast- and Concussion-Induced Tinnitus and Related Traumatic Brain Injury (TBI)

2013 ◽  
Author(s):  
Jinsheng Zhang ◽  
Anthony Cacace ◽  
E. M. Haacke ◽  
Bruce Berkowitz ◽  
Jiani Hu ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Animal Models

scholarly journals Unconventional animal models for traumatic brain injury and chronic traumatic encephalopathy

2021 ◽  
Author(s):  
Nicole L. Ackermans ◽  
Merina Varghese ◽  
Bridget Wicinski ◽  
Joshua Torres ◽  
Rita De Gasperi ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Animal Models ◽  
Chronic Traumatic Encephalopathy
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